Association of the major histocompatibility complex with response to infliximab therapy in rheumatoid arthritis patients

Arthritis Rheum. 2004 Apr;50(4):1077-82. doi: 10.1002/art.20154.


Objective: To determine whether major histocompatibility complex (MHC) polymorphisms are associated with a good or poor response to infliximab therapy in patients with rheumatoid arthritis (RA).

Methods: Seventy-eight infliximab-treated patients with RA were genotyped for HLA-DRB1, HLA-DQA1, HLA-DQB1, MHC class I chain-related gene A (MICA) transmembrane polymorphism alleles, and tumor necrosis factor a (TNFa), TNFb, TNFc, TNFd, TNFe, D6S273, HLA-B-associated transcript 2 (BAT2), and D6S2223 microsatellites. Chi-square tests were performed to compare allele proportions between responder and nonresponder patients. A control sample of 342 healthy individuals was also included to detect linkage disequilibrium between pairs of markers.

Results: Among responders, the frequency of the TNFa11;b4 minihaplotype was increased (41% versus 16% in nonresponders; P = 0.01) and that of the D6S273_3 allele was decreased (32% versus 56% in nonresponders; P = 0.04). The D6S273_4/BAT2_2 pair was much more frequently observed among responders (46% versus 11% in nonresponders; P = 0.001). When compared with controls, this pair of alleles was found to be associated only with the group of responder patients (46% in responders versus 17% in controls; P = 0.00002). Most of the time, these markers are present in a DRB1*0404/D6S273_4/BAT2_2/TNFa11;b4 context. No statistically significant differences were observed for MICA and D6S2223 polymorphisms and for shared epitope status.

Conclusion: The data suggest that genetic determinants of response to infliximab therapy exist in the HLA complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics*
  • Drug Resistance / genetics
  • Female
  • HLA-DQ Antigens / genetics
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Infliximab
  • Linkage Disequilibrium
  • Lymphotoxin-alpha / genetics
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • Phenotype
  • Proteins / genetics
  • Tumor Necrosis Factor-alpha / genetics


  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • HLA-DQ Antigens
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DQA1 antigen
  • HLA-DQB1 antigen
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Histocompatibility Antigens Class I
  • Lymphotoxin-alpha
  • Proteins
  • Tumor Necrosis Factor-alpha
  • PRRC2A protein, human
  • Infliximab