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 Table of Contents  
ORAL ABSTRACT
Year : 2022  |  Volume : 17  |  Issue : 5  |  Page : 1-24

Oral Abstract


Date of Web Publication26-Nov-2022

Correspondence Address:
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-3698.362015

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How to cite this article:
. Oral Abstract. Indian J Rheumatol 2022;17, Suppl S1:1-24

How to cite this URL:
. Oral Abstract. Indian J Rheumatol [serial online] 2022 [cited 2023 Jan 31];17, Suppl S1:1-24. Available from: https://www.indianjrheumatol.com/text.asp?2022/17/5/1/362015




  OP01 Top


Effect of an additional dose of COVID-19 vaccine in autoimmune rheumatic disease patients without SARS CoV-2 antibody seroconversion/inadequate seroconversion: A randomized controlled trial

Anuroopa Vijayan, Aswathy Sukumaran, Sara Jones1, Sakir Ahmed2, Pankti Mehta3, Aby Paul, Manju Mohanan, Kaveri Nalianda, Sanjana Joseph, K Narayanan, Padmanabha Shenoy; Dr Shenoys Care, Kochi, 1Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, 2Kalinga Institute of Medical Sciences, Bhubaneshwar, Odisha, 3King George's Medical University, Lucknow, Uttar Pradesh, India

Background: An additional dose of COVID-19 vaccine is being offered to vaccinated people, especially to those who are immunocompromised. In India, the most widely available vaccines are the adenoviral vector-borne AZD1222 (ChAdOx1 nCoV-19) and the heat-inactivated (BBV152). This study compared the efficacy between these two vaccines in patients with autoimmune rheumatic diseases (AIRD).

Objectives: To compare final anti-SARS-CoV-2 antibody titres, neutralization of pseudo-virions by these antibodies and T cell responses between patients of AIRD who had received the third dose of AZD1222 and BBV152 vaccines.

Methods: Patients with stable AIRD who had completed two doses of COVID-19 vaccination but had suboptimal response (anti-RBD antibody <212) were randomized (1:1) to receive either AZD1222 or BBV152 as a booster dose. Patients with previous hybrid immunity or those who developed COVID-19 during the trial were excluded. Antibody titres, neutralization of Wuhan and Omicron pseudo-virions and interferon release by T cells (ELISPOT) in response to the Spike antigen were measured four weeks after this booster dose. [Trial registration: CTRI/2021/12/038928].

Results: 146 were screened, 91 randomized and 67 analysed per protocol. The third dose [Figure 1] improved antibody titres [p<0.001], neutralization of Wuhan strain [p<0.001], and T cell interferon release [p<0.001] but not neutralization of the Omicron strain [p = 0.24]. Antibody titres were higher (p<0.005) after ADZ1222 boost [2414IU (IQR: 330-10315)] than BBV1222 [347.7IU (0.4-973)]. Neutralization of the Wuhan stain was better [AZD1222: 76.6% (23.0-95.45) versus BBV152:32.7% (0-78.9), p=0.03 by ANCOVA]. Neutralization of Omicron [0 (0-28.4) vs. 0 (0-4.8)] and T cell interferon release [57.0 IU (23.5-95) vs 50.5 (13.2-139)] were similar. The effects of the booster stratified by the primary vaccine used are presented in [Figure 2].
Figure 1: Third dose and antibody titres

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Figure 2: Final antibody titres and neurtralization

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Conclusion: The third dose improved all parameters of immunogenicity in AIRD patients with previous inadequate responses except Omicron neutralization. The vector born vaccine appears to be superior at least in terms of antibody titres and Wuhan strain neutralization.


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Comparison of intraarticular injection of glucocorticoid with and without local anesthesia in the overlying skin: A randomized controlled trial

Varun Dhir, Alan Shaji, Chandra Bhushan Prasad, Babita Ghai1, Shankar Naidu, Aman Sharma, Susheel Kumar, Shefali Sharma, Sanjay Jain; Department of Internal Medicine, Division of Rheumatology, Postgraduate Institute of Medical Education and Research, 1Department of Anesthesia and Critical Care, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Background: There is no consensus among rheumatologists on giving local anesthesia to the overlying skin prior to an intra-articular injection of glucocorticoid.

Objective: Compare procedural pain in intra-articular injection between using local anesthesia to overlying skin or not.

Methods: Open-label randomized controlled trial included patients with rheumatoid arthritis or spondyloarthritis undergoing intra-articular injections (of glucocorticoid) to paired medium-large joints. First the left joint was injected followed by right joint after a gap of 10-minutes. Randomization by software whether local anesthesia (5 ml of 2% Lignocaine using a 23G needle) would be given to the left or right joint. Primary endpoint was immediate procedural pain felt by the patient using the 'Numerical Rating Scale and Faces Pain Scale-Revised. Secondary endpoints were 1-h pain assessment, patient preference and complications. Paired t-test and Wilcoxon Signed Ranked test was used (paired data). Trial#CTRI/2021/07/034777.

Results: Included 42 patients undergoing paired joint injections; joints were knee (21 patients), wrists (14), ankles (5) and elbows (2). Most were middle aged with mean age (±SD) 44.6 ± 14 years, 71% being females having rheumatoid arthritis (37) and spondyloarthritis (5 patients). There was a significantly lower immediate procedural pain in the joint over which the skin was given local anaesthesia compared to that not (4.7 (1.7), 5.6 (1.6), p<0.01, difference -1.1, 95% CI -1.5 to -0.7) [Figure 1]. This was also reduced pain in the that joint at 1-hour post procedure (3.3 (1.4), 4.0 (1.6), p<0.01). Majority of patients (78.6%) preferred the procedure with local anaesthesia [Figure 2]. There was no difference in complications of hypopigmentation or purpura.
Figure 1: Immediate pain score in the joint given LA or not given LA in the overlying skin. **P < 0.01

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Figure 2: Patient preference for LA or not

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Conclusion: Local anaesthesia of the overlying skin led to a definite but modest reduction in pain felt by the patient during intraarticular injection.


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Autoantibodies in a multi-institutional Indian SLE inception cohort for research: Prevalence and cluster analysis

Amita Aggarwal, Rudrarpan Chaterjee, Ranjan Gupta1, Vineeta Shobha2, Liza Rajasekhar3, Ashish J Mathew4, Bidyut Das5, Avinash Jain6, Manish Rathi7, Parasar Ghosh8, K Chengappa9, Vir Singh Negi9, Ramnath Misra for the INSPIRE Group; Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 1Department of Rheumatology, AIIMS, New Delhi, 2Department of Clinical Immunology and Rheumatology, St John's Medical College Hospital, Bengaluru, Karnataka, 3Department of Rheumatology, Nizam Institute of Medical Sciences, Hyderabad, Telangana, 4Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, Tamil Nadu, 5Department of Medicine, SCB Medical College, Cuttack, Odisha, 6Division of Clinical Immunology and Rheumatology, SMS Medical College and Hospital, Jaipur, Rajasthan, 7Department of Nephrology, PGIMER, Chandigarh, 8Department of Clinical Immunology and Rheumatology, IPGMER, Kolkata, West Bengal, 9Department of Clinical Immunology, JIPMER, Puducherry, India

Background: SLE is characterized by an array of autoantibodies and their prevalence is variable across different ethnic group. Data on South Asian population is limited.

Methods: Data from patients enrolled in a multi-institutional Indian SLE inception cohort for Research (INSPIRE) were included in the study. At inclusion, autoantibodies were measured using Immunoline (Euroimmune) 17 antigen kit or ELISA. To determine clusters, random forest algorithm was used to generate a distance matrix between autoantibodies. This was plotted on a multidimensional scale and used to cluster the autoantibodies by a k-means approach.

Results: A total of 2033 patients (1866 females) with mean age of 27.5+10.22 years and median disease duration of 10 months were included [Table 1]. C3 and C4 complement were low in 1459 and 1172 patients. By ELISA the prevalence was: anti-dsDNA 1364/1931 (70.6%), IgG anti- beta-2 GPI 80/1665 (4.8%) IgM anti-beta 2 GPI 206/1363 (15.1%), IgG ACL [127/1536 (8.2%)], IgM ACL (126/1610 (7.8%)]. Lupus anticoagulant was present in 236/1162 (20.3%). By Immunoline assay, the positivity rate for antibodies was: dsDNA (36.7%), Nucleosome (42.5%), Histone (35.3%), Ro52 (37.8%), Ro60 (40.9%), La (12.1%), Ribosomal P (33.6%), nRNP (52.6%), Sm (43.6%), Scl70 (2.7%), PM-SCL (2.1%), Jo1 (1.1%), PCNA (4.6%), AMA-M2 (8.1%), and CENP-B (1.3%). Four clusters of autoantibodies were identified [Figure 1]. Cluster 1 had antibodies to dsDNA, histone and nucleosome (45.84% patients). Cluster 2 had antibodies to Sm, nRNP, Ro52, Ro60 and Ribosomal P (48.65% patients). Cluster 3 had autoantibodies to cardiolipin, β2GP1, lupus anticoagulant, La as well as AMA-M2 (4.62% patients). Cluster 4 included antibodies to Scl-70, Jo-1, PCNA, PM-SCL and CENP-B (0.89% patients). Autoantibody clusters suggest that antibodies to DNA and associated proteins have association with nephritis especially proliferative nephritis and serositis whereas antibodies against RNA associated proteins increase muco-cutaneous disease and cluster 3 is associated with immune cytopenias [Table 1].
Table 1: Univariate odds ratios for clinical manifestations associated with clusters identified

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Conclusion: The prevalence of anti-Sm and Ribosomal P antibodies is high in Indian population, this could be related to differences in genetics. Association of antibody cluster with clinical phenotype suggests the pathogenic role of these antibodies.


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Clinical and angiographic outcomes of mycophenolate versus methotrexate in South Asian patients of Takayasu arteritis: Results from a randomised controlled trial

Shivraj Padiyar, Debashish Danda, Ruchika Goel, Elizabeth Joseph1, Aswin M Nair, George Joseph2, Balavendra Antonisamy3; Departments of Clinical Immunology and Rheumatology, 1Radiology, 2Cardiology and 3Biostatistics, Christian Medical College, Vellore, Tamil Nadu, India

Background: There are limited studies addressing the efficacy of non-biological agents in Takayasu arteritis (TA), mainly in the form of case series and cohort studies. Data of superiority of one agent over the other is lacking.

Objective: To compare the clinical and angiographic responses of Mycophenolate Mofetil (MMF) versus Methotrexate in TA.

Methods: This was a single centre randomized, outcome assessor blinded trial. Adult patients of TA with active disease were randomized 1:1 to MMF 1g twice daily or Methotrexate 20 mg once weekly. The primary outcome was treatment response as defined by ITAS score at 9 months. Secondary end points included time to first failure and angiographic progression. An exploratory subgroup analysis was done to determine the various factors influencing the outcomes. The study was registered in the Clinical Trials Registry of India (CTRI) (The Universal Trial Number: U1111-1192-125).

Results: A total of 52 patients (26 in each arm) were recruited in the study. In the per-protocol analysis, the rate of responders as per the protocol defined criteria (primary outcome) was 71.43% (15/21) in the MMF arm and 63.64% (14/22) in the Methotrexate arm (p=0.58) [Table 1]. The median time to 1st failure was 9 months (Range: 3-9 months) in the MMF arm, whereas it was 4.5 (range: 3-9 months) in the Methotrexate arm (p=0.052) [Figure 1]. On comparing the angiographic outcomes, both groups had 15 % of patients (n=3) with progressive disease, whereas rest 85 % of patients either had improvement or stable disease (p=0.721). Claudication improved in 18/24 patients (75%) with immunosuppression. There were no serious adverse events in either arm.
Figure 1: Cumulative freedom from failure in the MMF and methotrexate groups

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Table 1: Comparison of primary and secondary outcomes by treatment groups

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Conclusion: Although the primary endpoint was not met, there was a longer time to the first failure with MMF (9 months versus 4.5 months, p=0.052). There were no differences in the angiographic outcomes between the two groups.


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Short-term effect of methotrexate on apolipoproteins and lipid profile in patients with active rheumatoid arthritis: Results from the methotrexate escalation in rheumatoid arthritis trial

Siddharth Jain, Varun Dhir, Bidylaxmi Leishangthem, Madhur Kalyan1, Indu Verma1, Shankar Naidu, Shefali Khanna Sharma, Aman Sharma, Sanjay Jain; Department of Internal Medicine, Division of Clinical Immunology and Rheumatology, Postgraduate Institute of Medical Education and Research, 1Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Background: The cardioprotective effect of MTX is well established, but whether this is just due to control of inflammation, or also via an effect on serum lipoproteins, is unclear. Although a few studies have studied the effect of the MTX on traditional lipid profile in RA,[1] there is no data on the effect of MTX on apolipoproteins which are better cardiovascular risk predictors.

Objectives: To determine the short-term effect of MTX on apolipoproteins and traditional lipid profile in active RA.

Methods: DMARD-naïve patients with active RA enrolled in the multicentre, RCT comparing different MTX escalation strategies in RA (MEIRA)[2] and for whom paired serum samples were available before and after MTX treatment were included. Serum apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG) were measured before and after 16 weeks of MTX. Proatherosclerotic indices (TC/HDL and ApoB/ApoA1) were calculated.

Results: 103 patients [mean age 40 (8) years, 93 (90%) females, mean BMI 25.1 (4.8) kg/m2, all non-smokers and non-alcoholics] were included. None had comorbid diabetes, coronary artery disease or were on hypolipidemic drugs. An increase in Apo A1 levels [mean 5.6 mg/dL (p=0.02)], and HDL levels [mean 1.6 mg/dL (p=0.04)] was seen after 16 weeks of MTX monotherapy. Although a numerical increase in levels of TC (mean 4.6 mg/dL, p=0.07), LDL (mean 2 mg/dL, p=0.34) and TG (mean 6.6 mg/dL, p=0.35) was also noted, these were not statistically significant. No obvious change in Apo B levels and TC/HDL ratio occurred with MTX therapy. However, the ApoB/ApoA1 ratio decreased significantly from 0.8 to 0.7 (p=0.002) with MTX [Table 1].
Table 1: Baseline and end of treatment values of apolipoprotein A1, apolipoprotein B, total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides and proatherosclerotic indices (total cholesterol/high-density lipoprotein and a apolipoprotein B/apolipoprotein A1)

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Conclusion: MTX led to a mild but significant increase in HDL, ApoA1 and a reduction in ApoB/ApoA1 over short-term. This could represent one of the mechanisms by which MTX exerts its cardioprotective effect.


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Juvenile onset SLE in India-data from a multi-institutional inception cohort of systemic lupus erythematosus

Amita Aggarwal, Nikhil C Gowda, Avinash Jain1, Liza Rajasekhar2, Parashar Ghosh3, Ashish J Mathew4, Chengappa G Kavadichanda5, Vineeta Shobha6, Ranjan Gupta7, Saumya Ranjan Tripathy8, Manish Rathi9, Able Lawrence; Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 1Department of Clinical Immunology and Rheumatology, SMS Medical College and Hospital, Jaipur, Rajasthan, 2Department of Rheumatology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, 3Department of Rheumatology, Institute of Post-Graduate Medical Education and Research, Kolkata, West Bengal, 4Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, Tamil Nadu, 5Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, 6Department of Clinical Immunology and Rheumatology, St John's Medical College Hospital, Bengaluru, Karnataka, 7Department of Rheumatology, All India Institute of Medical Sciences, New Delhi, 8Department of Rheumatology, SCB Medical College and Hospital, Cuttack, Odisha, 9Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

Background: Most Lupus cohorts across the globe have poor representation of patients from South Asia who are ethnically different.

Objectives: To explore the clinical features and autoantibodies in Juvenile onset SLE in India.

Methods: We used the electronic database of Indian SLE inception cohort for research (INSPIRE), which enrolls all new SLE patients satisfying the SLICC classification criteria seen in the rheumatology unit at 10 tertiary care hospitals. Juvenile onset SLE was defined as onset of symptoms before age 18 years. Demographic data, clinical features, and autoantibodies were analyzed and compared them with adult onset SLE as well as with other cohorts across the World.

Results: Among a total of 2033 patients there were 288 children (250 girls), the mean age of children was 14.7±2.3 years and the median disease duration was 8 (4-15) months. The three most common manifestations among children were Fever in 227 (78.81%), Non scarring alopecia in 221 (79.73%) and Oral ulcers in 195 (67.71%). Nephritis was seen in 102 (35.4%) and Major CNS disease in 42 (14.5%). Children had shorter duration of symptoms prior to diagnosis (8 months vs. 10 months) and lower female: male ratio (6.57 vs. 12.5). Fever, oral ulcers, acute cutaneous lupus erythematosus, seizures and autoimmune hemolytic anemia were significantly higher in pediatric SLE patients compared to adults. ENA antibodies profile: nucleosome 132, histones 108, Ro 52 98, Ro 60 101, La30, Ribosomal P 115, nRNP 144, Sm 123, Scl70 4, PM Scl 5, Jo1 3, CENP 4, PCNA 15, AMA 21. Indian patients compared to international cohorts had higher disease activity, higher prevalence of oral ulcers, discoid lupus, neurologic disease, and anti-Sm antibodies (p<0.05) [Table 1].
Table 1: Comparison between adults and children with systemic lupus erythematosus in Indian systemic lupus erythematosus inception cohort for research cohort

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Conclusion: As compared to adults besides mucocutaneous disease, AIHA and seizures are more common in children. In comparison to data from other cohorts, Indian children had more active disease and neurological manifestations.

References

  1. Shobha V, Aggarwal A, Rajasekhar L, Jain A, Gupta R, Das B, et al. Indian SLE inception cohort for research (INSPIRE): The design of a multi-institutional cohort. Rheumatol Int 2021;41:887-94.
  2. Smith EM, Rasul S, Ciurtin C, Al-Abadi E, Armon K, Bailey K, et al. Limited sensitivity and specificity of the ACR/EULAR-2019 classification criteria for SLE in JSLE?-Observations from the UK JSLE cohort study. Rheumatology (Oxford) 2021;60:5271-81.
  3. Wu CY, Li CF, Wu QJ, Xu JH, Jiang LD, Gong L, et al. Chinese systemic lupus erythematosus treatment and research group registry IX: Clinical features and survival of childhood-onset systemic lupus erythematosus in China. Chin Med J (Engl) 2017;130:1276-82.
  4. Rubinstein TB, Mowrey WB, Ilowite NT, Wahezi DM, Childhood Arthritis and Rheumatology Research Alliance INVESTIGATORS. Delays to care in pediatric lupus patients: Data from the childhood arthritis and rheumatology research alliance legacy registry. Arthritis Care Res (Hoboken) 2018;70:420-7.



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Major salivary gland ultrasound and elastography for assessment of disease activity in patients of primary Sjögren's syndrome

Kunal Chandwar, Juhi Dixit, Kriti Kishor, Prasanna Dogga, Digvijay Ekbote, Puneet Kumar, Urmila Dhakad; Department of Clinical Immunology and Rheumatology, King George Medical University, Lucknow, UP

Background: To assess major salivary gland involvement by ultrasonography and elastography in patients with Sjögren's syndrome, correlate the severity of ultrasonographic and elastographic involvement of major salivary gland with disease activity.

Methods: In 35 pSS patients, disease activity was assessed by the European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) and the EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI). The Salivary gland were assessed using the Hocevar and OMERACT score and Real time Elastography was performed for the salivary glands and were scored semi-quantitatively.

Results: 35 patients of primary Sjögren's Syndrome and 55 controls were included in the study. The patients were younger with a mean age (37.37±11.9). Mean USG scores were significantly higher (p < 0.001) in cases than controls including the Hocevar (13.94±15.61 vs 0.80±1.82), OMERACT (3.06 ± 3.59 vs 0.45±0.978) and Elastography score (6.37± 2.850 vs 0.35± 0.584). ESSDAI correlated with Hocevar Score (rho–0.801, p-<0.001), OMERACT (rho-0.793, p-<0.001) and (rho–0.538, p-<0.001). ESSPRI correlated with Hocevar Score (rho-0.737, p -< 0.001), OMERACT score (rho-0.702, p-< 0.001) and Elastography (rho-0.388, p-<0.001). The mean Hocevar Score was higher in patients with high disease activity (36.26±8.05) compared to moderate disease activity (16.83±15.59) and Low disease activity (4.62±6.76). All the scores differentiated well between high and activity efficiently (p<0.001), however for the OMERACT (p-0.113) and Elastography score (p-0.085) the difference between moderate and low disease activity was not Statistically significant. A multivariate linear regression analysis found an association with USG scores [Table 2].
Table 2: Comparison between juvenile onset systemic lupus erythematosus in Indian systemic lupus erythematosus inception cohort for research cohort with other cohorts from across the world

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Conclusion: The Hocevar score had a very strong correlation with disease activity. The Elastography scores moderate correlated with disease activity and duration of disease. There was a near-complete correlation of USG scores with Unilateral, Parotid and submandibular scores.


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Cognitive dysfunction in lupus: A cross sectional study from a tertiary care center in Southern India

Ramya Sri Kodali, Ramya Janardhana, Benzeeta Pinto1, Luke Salazar2, Vineeta Shobha; Departments of Clinical Immunology and Rheumatology and 2Psychiatry, St. John's Medical College Hospital, 1Department of Rheumatology, Manipal Hospital, Bengaluru, Karnataka, India

Background: Cognitive Dysfunction (CD) in Systemic Lupus Erythematosus (SLE), though highly prevalent varying from 20-80%, is less studied due to difficult to use and lengthy assessment tools. The Montreal Cognitive Assessment (MoCA) is a brief, user friendly screening tool to assess CD.[2]

Objectives: To estimate the prevalence of CD and to determine factors associated with CD in patients with SLE with or without Neuropsychiatric (NP) SLE.

Methods: We recruited 160 SLE patients, who attended our rheumatology outpatient clinic between March 2021-July 2022. Demographic variables, level of education, disease duration, cumulative steroid dose, clinical and lab profile were documented. All patients were administered the MoCA questionnaire and were further grouped based on cut-off values (>26/30) into presence or absence of CD.

Results: About half of our sample {87/160 (54%)} had cognitive dysfunction based on MoCA. The major lupus subtypes are depicted in [Table 1]. Overall, there were 52 (32.5%) patients with lupus nephritis and 33 (20.6%) with NPSLE. Cognitive dysfunction was noted in 45% of NPSLE and 83% of those without NPSLE. The commonly affected domains were delayed recall (82.5%), visuospatial dysfunction (67.5%) and memory (60.6%). Steroid dose and disease duration were not significantly associated with CD. In multivariate regression analysis, older age (OR=1.09; P=0.001) had higher odds to develop CD, while upper socioeconomic status (SES) (OR = 0.18; P = 0.001), and higher education (OR=0.43; P = 0.020) had lower odds to develop CD in SLE [Table 1] and [Table 2].
Table 1: Comparison of ultrasonography and elastography scores in cases and controls

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Table 2: Correlation, multivariable linear regression and logistic regression between European league against rheumatism Sjögren's syndrome disease activity index and European league against rheumatism Sjögren's syndrome patient reported index with ultrasonography scores and elastography scores

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Conclusions: CD was detected in more than half of our sample. Factors like age, SES and education and not lupus disease specific manifestations or steroid dosing are associated with the occurrence of CD.


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Childhood vasculitis at Chandigarh: 29 years' experience from a tertiary care centre in North India

Suprit Basu, Rakesh Kumar Pilania, T Abarna, P Vignesh, Deepti Suri, Anju Gupta, Ankur Kumar Jindal, Surjit Singh; Advanced Pediatrics Centre, Pediatric Allergy Immunology Unit, PGIMER, Chandigarh, India

Background: Primary vasculitides in childhood comprise 2-10% of all patients registered in pediatric rheumatology clinics. Prevalence of different types of vasculitis may vary from centre to centre. There is paucity of data in prevalence of childhood vasculitis from developing countries.

Aim: This study aims to report the pattern of childhood vasculitis seen in a tertiary care centre in North India over the last 29 years (1993-2021).

Patients and Methods: Review of records of all children registered in the Pediatric Rheumatology Clinic (PRC), Department of Pediatrics, Advanced Pediatrics Center, Post Graduate Institute of Medical Education and Research, Chandigarh, India was performed. Patients with vasculitis were included in the study and their data were analyzed.

Results: We registered 8070 patients in PRC in the last 29 years. Vasculitis accounted for 1707 patients. Secondary causes of vasculitis, undifferentiated vasculitis, and overlap syndrome, were excluded from the cohort. Most common vasculitis reported was Kawasaki disease (KD) (n=1076) followed by Henoch Schonlein purpura (HSP) (n=479). Takayasu arteritis (n=44) was the only large vessel vasculitis noted in our study group. Polyarteritis nodosa was seen in 40 cases. Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis was seen in 16 cases (5 c-ANCA+; 8 p-ANCA+). Incidence of HSP over the last 29 years was similar (12-20 cases/year), whereas the incidence of KD has seen a steady rise over the years. HSP was the commonest vasculitis till 2003, and since then KD has become the most common vasculitis of childhood in this part of the country. HSP incidence was highest during October-November, whereas KD in our cohort has highest incidence in the months of April and September, with a nadir in February.

Discussion: KD is the commonest childhood vasculitis followed by HSP at our centre at Chandigarh, North India. However, incidence of HSP may be more as milder cases may not have been referred from other institutes.
Table 1: Comparison of demographic parameters, clinical characteristics, and autoantibody profile among patients with and without cognitive dysfunction

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Association of toll like receptor-2 polymorphism (23 bp ins/del) with ankylosing spondylitis: A hospital based case-control study

Subrat Pradhan, Sukanya Priyadarshini Mohanty1, Rina Tripathy, Aditya Kumar Panda2, Saumya Ranjan Tripathy3, Bidyut Kumar Das3; Departments of Biochemistry, 1Medicine and 3Clinical Immunology and Rheumatology, SCB MCH, 2Department of Bioscience and Bioinformatics, Khalikote University, Cuttack, Odisha, India

Background: Ankylosing spondylitis (AS) is an inflammatory disorder where innate immunity and genetic predisposition has an important role in pathogenesis. Recently, a 23 bp ins/del polymorphism at 5'UTR of TLR-2 gene (rs111200466) has been documented, which is associated with high TNF-alpha levels (a major inflammatory marker in pathogenesis of AS). In this study we investigated the association of TLR-2 (23 bp ins/del) polymorphism and clinical severity in AS patients admitted in the Dept of Clinical Immunology & Rheumatology of SCB MCH, Cuttack.
Table 2: Results from univariate and multivariate logistic regression analysis

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Methods: AS patients (n=100) fulfilling Modified New York Criteria were enrolled along with 70 healthy age and sex matched controls from similar geographical areas. TLR-2 (23 bp ins/del) genetic distribution was observed and analysed with respect to inflammatory markers (ESR, CRP and TNF-α) and disease severity indices (BASDAI, BASFI, ASDAS-ESR & ASDAS-CRP).

Results: The mean age of AS patients and healthy controls was 31.7 ± 9.5 and 31.5±8.4 years, respectively. At the time of enrolment, mean disease duration of patients was 4.3±3.8 years. Distribution of TLR2 (23 bp ins/del) polymorphism was in accordance with Hardy-Weinberg Equilibrium. Prevalence of del/del genotype was significantly higher in AS patients compared to healthy controls (P=0.04, OR=0.14), indicating a possible contributory role of TLR2 on predisposition to AS. Significant association of TLR-2 (23 bp ins/del) polymorphism was also observed with inflammatory markers (ESR, CRP and TNF-α) and disease severity indices (BASDAI, BASFI, ASDAS-ESR & ASDAS-CRP).

Conclusion: TLR2 (23 bp del/del) homozygous was significantly associated with AS patients and high disease severity.


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C4 gene copy number variations in systemic lupus erythematosus

Christina Mariaselvam1, Gaurav Seth1, Rajagopal Krishnamoorthy2, Ryad Tamouza2, Vir Singh Negi1,3; 1Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, 2Department of Clinical Immunology and Rheumatology, All India Institute of Medical Sciences, Bilaspur, Himachal Pradesh, India, 3Univ Paris Est Creteil, INSERM UMR, IMRB, Translational Neuropsychiatry, AP-HP, DMU IMPACT, FHU ADAPT, Fondation FondaMental, Créteil, France

Background: Systemic Lupus Erythematosus (SLE) is characterized by low levels of serum C3 and C4. Low complements may either be due to increased consumption or decreased synthesis, the exact mechanisms of which is unknown. C4 gene exists as genetically homologous isoforms that might dysregulate complement protein expression.

Objectives: To characterize the genetic diversity of the C4 gene and correlate with serum complement levels.

Methods: 70 SLE and 90 controls were enrolled. Genomic DNA was used to characterize CNVs of the C4AL, C4AS, C4BL, C4BS using droplet digital PCR. Serum C3 and C4 levels were also quantified. Chi-square and Spearman's nonparametric tests were used for analysis.

Results: Two copies of C4A and C4B genes were frequent. We did not observe C4 null allele. On comparison between cases and controls, we found that the C4B gene and its short forms (C4BS) were abundant in SLE, while C4A, its long form (C4AL), was abundant in controls [Figure 1]a and [Figure 1]b. We observed 34 different C4-HERV genotypes, of which 7 were at a frequency greater than 5%. This cohort's most common C4 genotype was AL-AL-BL-BS [33%, [Table 1]]. Though the frequency of this genotype was overrepresented in SLE, the difference was not statistically significant. The AL-AL-AL-BS genotype was significantly higher in controls than SLE (9% vs 1%, p=0.04). There was no correlation between the C4 and C4-HERV gene copy numbers and serum levels of complement.
Figure 1: (a) Genetic diversity of C4 gene in systemic lupus erythematosus, (b) Genetic diversity of C4-HERV gene in systemic lupus erythematosus

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Table 1: C4 genotype frequency in cases and controls

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Conclusion: Our data show that, although the C4A and C4B gene diversity is different between cases and controls, it does not correlate with serum complement levels in SLE, suggesting that low complement levels could be because of its excessive consumption as a result of complement activation. We also observed an absence of C4 null allele in this cohort. Our findings need further validation in a larger homogenous SLE cohort.


  OP12 Top


Pharmacogenomic evaluation of rituximab and cyclophosphamide response in anti-neutrophil cytoplasmic antibody associated vasculitis

Prateek Deo, Aman Sharma, Shankar Naidu, Prateek Bhatia, Dignata Das, Jithin Mathew, J Sankar, Varun Dhir, Shefali Khanna Sharma, Sanjay Jain; Department of Internal Medicine (Rheumatology Wing), PGIMER, Chandigarh, India

Background: The genetic determinants of treatment response in the cases of AAV are widely unknown. The relationship between the genes affecting pharmacogenetics of small vessel vasculitis and its implications in context of therapeutic complications.

Objectives: To study the polymorphism of various genes involved in treatment response of Rituximab and Cyclophosphamide in AAV and correlate the genetic polymorphism of AAV patients with Rituximab and Cyclophosphamide treatment response.

Methodology: This study was a prospective cohort study in which 97 patients [Figure 1] of AAV (GPA, MPA and EGPA) enrolled in the Department of Internal Medicine (Clinical Rheumatology and Immunology division) at PGIMER, Chandigarh. The single nucleotide polymorphisms of FcγRIIIA, FcγRIIA, FcγRIIB, CYP2C19*2 and CYP2B6 were analysed using multiplex PCR and sanger sequencing. The treatment response for rituximab and cyclophosphamide induction was analysed for the status of remission at the end of six months and complete remission status was analysed at the time of end of study period. The data of time to remission and complete remission, relapsing diseases and organ involvement at time of relapse was also corelated with tested genes polymorphism.
Figure 1: The details of induction treatment received in the study population

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Results: FCγRIIA the variant (v) allele frequency was more than wild allele (W) frequency in the study population [Figure 2]. Statistically significant differences significant (p value: 0.006) for allele frequency for the SNPs FCγRIIIA variant type/ (FcgRIIIa 559T) between the patients who attained complete remission and those not. The time to achieve remission/complete remission was significantly lower in FCγRIIA variant genotype polymorphism (FcgRIIa 519AA). Statistically significant hazard ratio was calculated for FcGRIIA variant type/ FcgRIIa 519AA with time to remission and complete remission with values HR = 4.55 (p value: 0.001), and HR = 11.18 (p value: 0.001) respectively.
Figure 2: The Kaplan Meir plots and results for remission/complete remission event for FcγRIIA gene

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Conclusions: Highly significant association of SNPs of FcγRIIa variant/519AA genotype with early remission and complete remission after induction treatment with rituximab was noted. This data could further help in tailored treatment of AAV patients and may also serve as a prognostic marker.


  OP13 Top


Longitudinal effect of cyclophosphamide-based treatment on Type I interferon gene signature in proliferative lupus nephritis

B Sree Nethra1, Sanket Shah,2 K G Chengappa1, Christina Mary Mariaselvam,1 K T Harichandra Kumar3, Molly Mary Thabah,1 Vir Singh Negi1,4; Departments of 1Clinical Immunology and 3Biostatistics, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, 2GCS Medical College, Ahmedabad, Gujarat, 4All India Institute of Medical Sciences, Bilaspur, Himachal Pradesh, India

Background: Studies understanding the effect of cyclophosphamide (CYC)-based regimens on type-I IFN signature in proliferative lupus nephritis (LN) are limited. The role of interferons (IFNs) in predicting treatment outcome in LN is also largely unexplored.

Objectives: To assess the longitudinal effect of CYC-based regimens on Type-I IFN signature in proliferative LN and its role in predicting treatment response.

Methods: Treatment-naïve biopsy proven proliferative LN scheduled to receive high-dose (HD) or low-dose (LD) CYC were recruited and followed up for 6-months between 2018-2022. Treatment outcome was classified as responders (CR) and non-responders (NR) using EULAR/EDTA criteria. Total RNA was extracted from PBMCs at baseline, 3 and 6-months. An IFN-score (ISG) was developed from the mean log-transformed values of relative gene expression of 7 IFN-genes (MX1, OAS1, IFIT1, OASL, IFIT4, LY6E, IRF7) at the above timepoints. Longitudinal changes within and between groups was measured using one-way RM-ANOVA and two-way RM-ANOVA, with post-hoc analysis and Bonferroni's correction. Binary logistic regression analysis was used to identify independent predictors of non-response.

Results: The ISG significantly decreased from baseline to 6 months [Figure 1] within both HD (p=0.001) and LD-group (p<0.001) but not between groups (p=0.497). Within both groups, significant decrease was seen from baseline to 3-months (p=0.001 and p<0.001) followed by increase from 3 to 6-months (p=0.3 & p=0.03). This decrease at 3-months was not significant between both groups (p=0.253) and was independent of steroid dose (p=0.244). There was a decrease from baseline to 3-months (p<0.001 and p=0.046) and increase from 3 to 6-months (p=0.006 and p=1) within CR and NR. The overall decrease was significant between both groups (p=0.042). Relative change in ISG at 3-months [Table 1] was one of the independent predictors of non-response.
Figure 1: Serial changes in ISG score at different time points across treatment and response groups. (a) Overall, there was a significant decrease in ISG from baseline to 6 months (P < 0.001). (b) Serial changes from baseline to 6-months in HD-CYC group. (c) Serial changes from baseline to 6-months in LD-CYC group. (d) Change in ISG at 3-months in HD and LD-CYC group. (e) Serial changes from baseline to 6-months in CR group. (f) Serial changes from baseline to 6-months in NR group. (g) Relative change in ISG from baseline to 3m in CR and NR groups. CYC: Cyclophosphamide, HD: High dose, LD-Low dose, ISG score: Interferon gene signature score

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Table 1: Univariate logistic regression analysis

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Conclusion: Both CYC-based regimens decreased IFN-gene signature in LN. Relative change in ISG at 3-months was an independent predictor of non-response. Clinical relevance of this finding needs further validation.


  OP14 Top


Transcriptomics of treatment naïve multi-inflammatory syndrome in children as compared to healthy controls, kawasaki disease and systemic juvenile idiopathic arthritis

M V Prakashini, Sibabratta Patnaik, Krushna Chandra Murmu1, Soumendu Mahapatra1, A Raj Kumar Patro, Punit Prasad1, Sakir Ahmed; Department of Clinical Immunology and Rheumatology, Kalinga Institute of Medical Sciences, 1Department of Clinical Immunology and Rheumatology, Institute of Life Sciences, Bhubaneswar, Odisha, India

Background: Multi-inflammatory Syndrome in Children (MIS-C) is a rare but new entity temporarily associated with COVID-19. It is a highly inflammatory state with multi-organ involvement resembling incomplete Kawasaki Disease (KD). The pathogenesis is not completely known.

Objectives: To analyse the gene expression patterns of MIS-C and compare with that of healthy control (HC), KD and systemic Juvenile Idiopathic Arthritis (sJIA).

Methods: Next-generation sequencing using the RNAseq technique was carried out from the whole blood of six treatment naïve patients meeting the WHO criteria for MIS-C. For comparison, RNAseq transcriptomics data of 5 HC, 4KD and 7 sJIA was obtained from the Sequence Read Archive (SRA). These were processed via standard bioinformatics pathways and the DEseq2 library from R was used to analyse and annotate differentially expressed genes between the 4 groups. p-value was corrected by False Discovery Rate (FDR<0.05).

Results: The median age of the patients with MIS-C was 12 (IQR:7-13) years with 4 (66%) females. Two each had mild, moderate, and severe MIS-C clinically. In the PCA analysis [Figure 1]a, MIS-C clustered separately from HC, KD and sJIA, demonstrating its unique gene expression profile. [Figure 1]b shows the top 20 genes that were responsible for the separation of the clusters (cos2>0.98). As compared to HC, there were 12754 genes upregulated and 4643 downregulated in MIS-C [Figure 2]a. Compared to KD, 5016 were upregulated and 6367 downregulated (b). Again, in comparison with sJIA, 14062 were upregulated and 5331 were downregulated (c). Amongst the top 50 genes with lowest FDR and highest log2FoldChange in the three comparisons, common genes were: TMCC2, ITGA2B, DMTN, GFI1B, PF4, QSER1, GRAP2 and TUBB1.
Figure 1: Principle component analysis showing clustering of the four different samples groups. MIS-C-Multi-inflammatory syndrome in children; HC: Healthy controls, KD: Kawasaki disease, sJIA: Systemic juvenile idiopathic arthritis

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Figure 2: Volcano plots showing log2 (Fold Change) versus log10 (FDR) with upregulated genes (>3 fold versus reference group) in red, downregulated genes (>-3fold vs. reference group) in blue and genes with unchanged expression in gray

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Conclusions: Whole blood transcriptomics has identified unique gene expression signatures for MIS-C. Further work is required to elucidate the role of the top genes and gene sets in the pathogenesis of this novel, enigmatic entity.


  OP15 Top


Utility of circulating immune complexes, cytokines, and monocyte subset analysis in SLE

Avanish Jha, Josna Joseph, Savit B Prabhu1, Bijesh Yadav2, Anita Chaudhary1, John Mathew; Department of Clinical Immunology and Rheumatology, 1Wellcome Research Laboratory, 2Department of Biostatistics, Christian Medical College, Vellore, Tamil Nadu, India

Background: Systemic lupus erythematosus (SLE) is a heterogeneous disease with interaction of innate and adaptive immunity in pathogenesis and clinical activity. Although Complement levels and dsDNA levels are used for monitoring, there is a need for newer prognostic markers in SLE management.

Objective: To assess the prognostic utility of circulating immune complex (CIC) against C1q, cytokines like Tumour necrosis factor-alpha (TNF-a), Transforming growth factor-beta (TGF-b), interleukin-6 (IL-6) and monocyte subset analysis in lupus.

Methods: We conducted a prospective observational study in patients with SLE and no flare (as per SELENA-SLEDAI score =>4). A single visit interview of patients along with routine laboratory reports was used to select samples. A voluntary written consent was obtained, and a blood sample (10 ml) was collected to separate peripheral blood mononuclear cells (PBMC) and Serum. Cell analysis for monocyte subtypes was done using antibodies against cell surface markers using Fluorescence-activated cell sorting (FACS). Monocyte was sorted as classical and non-classical by CD14 and CD16 expression. Serum cytokines levels of IL-6, TNF-α, TGF-β and circulating immune complexes (CIC) were measured using ELISA kits.

Results: Among the 42 patients of SLE [Table 1], 22 had active disease and 15 were newly diagnosed cases. The median age was 31 years (IQR 22.75 to 39.25) and the disease duration was 22 months (IQR 0-70.5). Musculoskeletal (76.2%), mucocutaneous (69%), renal (52.4%) and neuropsychiatric involvements (26.2%) were the common organ system involvements. TNF alpha levels [Table 2] was elevated in active disease (p=0.042) but other cytokines didn't correlate with disease status. CIC levels significantly differentiated active from inactive disease (p=0.000. Total monocytes were significantly reduced in active disease and Intermediate monocyte subset was numerically increased but not statistically different in active group (p=0.09). Mean fluorescence intensity (MFI) of CD 163 was however, significantly elevated in active disease.
Table 1: Patient characteristics

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Table 2: Results - Monocyte subset analysis and ELISA

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Conclusion: CIC along with TNF alpha levels might be a novel valuable predictors of disease activity whereas other serum cytokine levels did not correlate with SLEDAI-based activity. Intermediate subset of monocytes was increased numerically, and their marker CD 163 MFI was significantly increased in active SLE and should be evaluated in further studies.


  OP16 Top


Comparison of presentation of pediatric-onset and adult-onset Takayasu arteritis: A retrospective cohort study

Darpan R Thakare, Upendra Rathore, Manas Ranjan Behera1, Dharmendra Bhadauria1, Neeraj Jain2, Manish Ora3, Sanjay Gambhir3, Sudeep Kumar4, Vikas Agarwal, Durga Prasanna Misra; Departments of Clinical Immunology and Rheumatology, 1Nephrology, 2Radiodiagnosis, 3Nuclear Medicine and 4Cardiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Background: To compare the clinical profile of pediatric-onset and adult-onset Takayasu arteritis (TAK).

Methods: Data related to demographics, clinical, laboratory, and angiographic features of pediatric (age ≤18 years) and adult-onset TAK patients from a retrospective cohort in a tertiary care hospital were recorded and compared. Waiver of written informed consent was obtained from the ethics committee for retrospective retrieval of data.

Results: Out of 166 patients [Table 1] (47 pediatric and 116 adult-onset TAK patients), majority of the patients were females with a mean age of onset of 14 years and 30 years and a mean age of diagnosis of 18 years and 33 years, respectively. Results show that arthralgias (p=0.033), chest pain (p=0.046) and heart failure (p=0.017) were more common in pediatric-onset TAK patients, while strokes (p=0.049) were more frequent in adult-onset TAK patients. The angiographic findings [Table 2] were different with renal artery involvement more frequent in pediatric-onset TAK patients (p=0.008) and adult-onset TAK patients had frequent aortic arch disease (Type 1 HATA) (p=0.038). More adult-onset TAK patients underwent PET-CT for evaluation of disease activity (p=0.053).
Table 1: Demographic profile, clinical, laboratory parameters of pediatric and adult-onset Takayasu arteritis patients

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Table 2: Angiographic findings of pediatric and adult-onset Takayasu arteritis patients

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Conclusion: Pediatric onset TAK patients are more likely to have arthralgia, chest pain, heart failure, and renal artery involvement. Stroke and aortic arch disease are more common in adult-onset TAK patients.


  OP17 Top


How accurate is teleconsultation in assessing disease activity in patients with rheumatoid arthritis? A pilot study

Sandeep Yadav, Asna Shaikh, C Balakrishnan; P. D. Hinduja National Hospital and Medical Research Centre, Mumbai, Maharashtra, India

Background: With the rapid adaptation of telemedicine there is a need for new tools for virtual examination in rheumatology practice.

Aims: To evaluate the level of agreement between virtually calculated disease activity by novel musculoskeletal (MSK) examination method with standard MSK examination method in RA patients.

Methods: 30 (29 females) follow-up patients of RA (ACR 2010) attending the rheumatologic OPD clinic of a tertiary health care hospital were recruited over one month. Their disease activity was independently calculated, first via a novel Virtual MSK examination method (Virtual DAS 28 ESR/CDAI), followed by a standard in-person method (DAS 28 ESR /CDAI) by two different examiners blinded to each other's findings.

Results: The reliability of assessments between the two examiners as judged by inter-class correlation was excellent for DAS–28 ESR and CDAI weight (ICC > 0.9), good for the total tender joint count and swollen joint count (ICC 0.75-0.91), and moderate for global physician assessment (0.50-0.75). The level of agreement tested using a Bland Altman plot showed that the mean absolute difference (bias) between Virtual DAS ESR 28 and DAS 28 ESR was 0.084 (% 95 CI -0.05782 to 0.2265) with p = 0.2348, which was well below the minimal clinically important difference (MCID) for DAS-ESR, which was 1.2, suggesting an acceptable level of agreement. Similarly, the mean absolute difference (bias) between Clinical disease activity index (CDAI), and Virtual CDAI was 0.9667 (% 95 CI-0.1705 to 2.1039) with P=0.0927, which was well below the MCID for CDAI, which is 12, suggesting an acceptable level of agreement. There was a significant difference in the level of agreement concerning the total number of swollen joints counted [Table 1].
Table 1: Method of online virtual examination

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Table 2: Mean arithmetic differences across individual joint counts derived from Bland-Altman plot

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Recommendation: In terms of disease activity and the total number of tender joint counts, our novel virtual MSK test was comparable to an in-person MSK examination. There was some variability in the swollen joint count, but the new approach provided good reliability and showed an acceptable level of agreement.


  OP18 Top


Study of metabolic profile and common carotid intima media thickness in patients with psoriatic arthritis

Digvijay Ekbote, Kriti Kishor, Kunal Chandwar, Dogga Prasanna Kumar, Juhi Dixit, Urmila Dhakad, Puneet Kumar; Department of Clinical Immunology and Rheumatology, King George Medical University, Lucknow, Uttar Pradesh, India

Background: Psoriatic arthritis (PsA) is associated with a higher burden of cardiometabolic disorders compared with the general population. Increase in cardiovascular risk in patients with PsA denotes role of systemic inflammation.

Objectives: (1) To evaluate prevalence of Metabolic Syndrome, Insulin Resistance and their association with disease activity in patients with PsA. (2) To evaluate extent of subclinical atherosclerosis and its comparison with healthy controls by the means of carotid intima media thickness measurement through USG.

Methods: Total 54 patients and 27 controls were included in the Study. (1) Metabolic profile was assessed by NCEP ATPIII 2004 criteria. (2) CIMT: Mean CIMT was measured by USG. (3) HOMA-IR was used to quantify insulin resistance. (4) Disease activity was measured by Composite Psoriatic Disease Activity Index (CPDAI).

Results: All patients who fulfilled criteria metabolic syndrome [Table 1] had central adiposity and impaired fasting glucose /diabetes mellitus (19/19) > Hypertriglyceridemia (17/19) > Hypertension (16/19) > Decreased HDL (10/19). Patients of PsA with metabolic syndrome had higher CIMT [Figure 1] mean 0.73 ± 0.10 (Mean ± SD) than those who did not have metabolic syndrome 0.62 ± 0.07 (p< 0.001). Patients with PsA had higher CIMT when compared to matched controls (mean ± SD 0.65 ±0.10 mm vs 0.45 ±0.06 mm; p<0.001. Mean CIMT value did not correlate with disease activity.


  OP19 Top


Clinical profile and outcome of COVID 19 related MIS-c: A prospective cohort study from three tertiary care centers in Kerala, India

D R Spoorthy Raj, Suma Balan, Arun Tiwari1, V F Johny2, Abdul Rauf3, Sajith Keshavan4, Sumanth Madan, Sekhar Easwar, Abhish Sudhakar5; Departments of Rheumatology and Clinical Immunology, 4Pediatric Pulmonology and Critical Care and 5Biostatistics, Amrita Institute of Medical Sciences, 1Apollo Adlux Hospital, 2Medical Trust Hospital, 3Baby Memorial Hospital, Kochi, Kerala, India

Background: MIS-c, is a post viral hyperinflammatory state characterized by multi-system inflammation and is potentially life threatening without timely treatment.

Objectives: To delineate the clinical profile and determine factors associated with severe disease.

Methods: 130 children, fulfilling the CDC criteria for MIS-c, hospitalized in 3 different tertiary care centers in Kerala, between 2019 and 2021, were included in the study. Clinical, lab profile, treatment strategies and immediate outcome measures were retrieved from EMR.

Results: A total of 130 cases with 70 (53.8%) males were included in the study. Mean age at presentation was 7.21 +/- 4.49 years. Median duration of fever was 5 days. Most common organ manifestation was GI involvement (83.1%) followed by mucocutaneous manifestations (78.55%). Cardiovascular involvement was observed in 70 (53.8%) of cases, most common being coronary abnormalities (24.6%). Interestingly 2 (1.53%) cases were detected to have hemodynamically significant brady-arrhythmias requiring permanent pacing support. Details of clinical profile are provided in [Figure 1] and lab profile and outcome measures in [Table 1]. 53.81% of cases were classified as Severe MIS-c, based on hemodynamic compromise. 88.5% required ICU care. 17.7%, 49.2%, 0.7% required invasive mechanical ventilation, inotrope support and ECMO respectively. Most cases were managed with combined IVIg and steroids along with LDA and anticoagulation as deemed necessary. 1 case required Infliximab in view of progressive coronary aneurysm. Mortality rate in our cohort was 1.53%. 84.6% recovered without sequelae and 13.8% with sequelae, in the form of persistent coronary and conduction system abnormalities. Combined gastro-intestinal and mucocutaneous manifestations, elevated cardiac biomarkers, thrombocytopenia, elevated CRP (>100), hyperferritinemia and hypoalbuminemia were found to be associated with severe disease.
Figure 1: CIMT

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Table 1: Parameters and their mean values included in the study

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Conclusion: MIS-c warrants early diagnosis and severity prediction considering the rapid course and high mortality. Upfront combination therapy with IVIg and steroids with prompt intensive care is crucial for good clinical outcomes.
Figure 1: Clinical profile

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  OP20 Top


Efficacy and safety of rituximab in lupus nephritis: Indian data

G Manikandan, John Mathew, U Shivraj Padiyar; Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, Tamil Nadu, India

Background: Current KDIGO and EULAR/ERA-EDTA guidelines recommend immunosuppression including corticosteroids, cyclophosphamide or mycophenolate mofetil (MMF) as first-line agents for remission induction in lupus nephritis. However, with current induction regimens, <60% of Class III to V patients with lupus nephritis achieve a complete response. Thus, despite being a major contributor to kidney related morbidity, lupus nephritis is still in need of more effective therapeutic interventions.

Objectives: Rituximab has been used off-label for various glomerular diseases. No Indian data are available to demonstrate the efficacy of rituximab in lupus nephritis. We evaluated rituximab as a potential therapeutic agent in lupus nephritis in Indian patients.

Methods: Single centre, retrospective study, involving 126 patients with class III, IV or V lupus nephritis. Rituximab was given at a dose of 1 g on days 1 and 15 with or without pulse methylprednisolone as induction agent. Patients with missing data are excluded in analysis.

Results: 85 out of 113 (75%) patients achieved complete or partial remission with a sustained response in 82 out of 96 (85%) at 1 year. Mean steroid dose in prednisolone equivalent at 0, 3, 6, 12 months are 55, 19.95, 4, 55, 0.75 mg respectively. Significant reduction in other parameters like dsDNA, c3, c4, urine RBC, were recorded on treatment with rituximab. The complication rate was low with no severe infections or death. Subgroup analysis between 17 patients who received direct rituximab and those who received rituximab after treatment failure or relapse with either induction agents like cyclophosphamide and MMF didn't show any statistical difference in results including CKD, dialysis requirement or death.
Table 1: Laboratory profile, outcome measures and treatment profile

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Conclusion: These results indicate the possible efficacy and safety of rituximab-based regime with its potential to reduce the steroid requirement as well as achieving remission in treatment naïve and in patients who are refractory or relapse with standard agents.


  OP21 Top


Association between knee MR imaging markers and knee symptoms over 7 years in young adults

Ambrish Singh1, Alison Venn1, Leigh Blizzard1, Lyn March2,3, Flavia Cicuttini4, Felix Eckstein5,6,7, Graeme Jones1, Changhai Ding1,4,8, Benny Antony1; 1Menzies Institute for Medical Research, University of Tasmania, Hobart, 2Institute of Bone and Joint Research, Kolling Institute of Medical Research, University of Sydney, 3Department of Florance and Cope Professorial Rheumatology, Royal North Shore Hospital, University of Sydney, St Leonards, Sydney, 4Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, 6Department of Imaging and Functional Musculoskeletal Research, Institute of Anatomy and Cell Biology, Paracelsus Medical University Salzburg and Nuremberg, 7Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Paracelsus Medical University, Salzburg, Austria, 8Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, China, 5Chondrometrics GmbH, Ainring, Germany

Background: There is conflicting evidence on the association between knee MRI-based morphological markers and knee symptoms.

Aim: To investigate the associations between MR imaging biomarkers and knee symptoms in middle-aged adults followed over seven years.

Method: Knee symptoms were assessed using the WOMAC scale during Childhood Determinants of Adult Health (CDAH)-knee study at baseline (year: 2008-10; age: 30–40 years) and 6–9-year follow-up (CDAH-3; year: 2014–2019; age: 36–49 years). Knee MRI scans were obtained at baseline and were assessed quantitatively for morphological markers–cartilage volume, cartilage thickness, subchondral bone area. Cartilage defects and BMLs were assessed semi-quantitative scoring systems. Univariable and multivariable (adjusted for age, sex, and BMI) zero-inflated Poisson (ZIP) regression model with random effects were used to describe cross-sectional and longitudinal associations.

Results: The prevalence of knee pain at baseline (mean age (SD): 34 (2.7); female: 49%) was 34% that increased to 50% over 6–9-year follow-up (age: 43 (3.2)). Cross sectionally, there was a weak but statistically significant negative association between medial femorotibial compartment (MFTC) [RoM=0.99971084; 95%CI: 0.9995525, 0.99986921; p<0.001], lateral femorotibial compartment (LFTC) [RoM=0.99982602; 95%CI: 0.99969915, 0.9999529; p=0.007], and patellar cartilage volume [RoM=0.99981722; 95%CI: 0.99965326, 0.9999811; p=0.029] with knee symptoms. Similarly, there was a negative association between patellar cartilage volume (RoM=0.99975523; 95%CI: 0.99961427, 0.99989621; p=0.014), MFTC cartilage thickness (RoM=0.72090775; 95%CI: 0.59481806, 0.87372596; p=0.001) and knee symptoms assessed after seven years. The total bone area was consistently and negatively associated with knee symptoms at baseline [RoM=0.9210485; 95%CI: 0.8939677, 0.9489496; p<0.001] and over seven years (RoM=0.9588811; 95%CI: 0.9313379, 0.9872388; p=0.005). Presence of any cartilage defect or BML was associated with higher knee symptoms at baseline and after seven years.

Conclusion: In the middle-aged adult population, BML and cartilage defects were positively associated with knee symptoms, whereas cartilage volume and thickness at MFTC and total bone area were weakly and negatively associated with knee symptoms. These results suggest that the quantitative and semi-quantitative MR imaging biomarkers can be explored as a marker of the clinical progression of OA in a young adult population.




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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13]
 
 
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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11], [Table 12], [Table 13], [Table 14], [Table 15], [Table 16], [Table 17], [Table 18], [Table 19]



 

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