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Association of HLA-E*01:01/*01:03 polymorphism with methotrexate-based treatment response in South Indian rheumatoid arthritis patients
Christina Mary Mariaselvam1, Aparna Sundaresh2, Arij Ben Chaaben3, Sofiane Salah3, Catherine Fortier4, Dominique Charron5, Rajagopal Krishnamoorthy3, Ryad Tamouza5, Vir Singh Negi2
1 Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry 605 006, India; INSERM, UMRS 1160, Saint Louis Hospital, Paris F75010, France
2 Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry 605 006, India
3 INSERM, UMRS 1160, Saint Louis Hospital, Paris F75010, France
4 Jean Dausset Laboratory of Immunology and Immunogenetics and LabEx Transplantex, Saint Louis Hospital, Paris
5 INSERM, UMRS 1160, Saint Louis Hospital, Paris F75010, France; Jean Dausset Laboratory of Immunology and Immunogenetics and LabEx Transplantex, Saint Louis Hospital, Paris F75010, France
Correspondence Address:
Vir Singh Negi
Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry 605 006, India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.1016/j.injr.2014.08.002
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Objectives: Non-classical HLA-E molecules may influence the disease susceptibility and phenotype including treatment response in chronic inflammatory disorders such as Rheumatoid Arthritis (RA) by virtue of their capacity to modulate innate immune pro- cesses. This study was carried out to investigate the role of HLA-E polymorphism in RA susceptibility, clinical and serological phenotype as well as treatment response.
Methods: Genomic DNA from 221 RA patients and 200 healthy controls (HC) were typed for HLA-E rs2844724 (C/T) and rs1264457 (HLA-E*01:01/*01:03) single nucleotide polymorphisms (SNPs) using the TaqMan 5'nuclease assay consisting of allele-specific fluorogenic oligo- nucleotide probes.
Results: Our study did not find any association between HLA-E polymorphism and RA susceptibility or disease phenotype. However, it was observed that the frequency of HLA- E*01:03 allele was higher in all RA cases (Pc ¼ 0.03,OR ¼ 3.02, 95% CI ¼ 1.06e9.39), young onset RA (YORA) (Pc ¼ 0.03, OR ¼ 3.20, 95% CI ¼ 1.11e9.98) and female RA (Pc ¼ 0.04, OR ¼ 3.04, 95% CI ¼ 1.06e9.46) patients who responded well (good responders) to a com- bination of non-biological disease modifying anti rheumatic drugs (DMARDs), metho- trexate (MTX) and hydroxychloroquine (HCQ) as compared to non-responders. Moreover, the frequency of rs2844724 T allele and TT genotype was observed to be higher in patients with low titers of rheumatoid factor (RF) than those with high titers (90% vs. 77% and 79% vs. 59% respectively), although the difference did not reach statistical significance. Conclusion: The results of our study suggest that HLA-E rs1264457 may influence the patient response to treatment with methotrexate-based DMARD therapy. Thus, it may be a useful genetic marker for treatment response in patients with RA. |
