Killer immunoglobulin-like receptor and human leukocyte antigen-C genotypes in rheumatoid arthritis primary responders and non-responders to anti-TNF-α therapy

Cathy M. McGeough, Daniel Berrar, Gary Wright, Clare Mathews, Paula Gilmore, Rodat T. Cunningham, Anthony J. Bjourson

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16 Citations (Scopus)


The identification of patients who will respond to anti-tumor necrosis factor alpha (anti-TNF-α) therapy will improve the efficacy, safety, and economic impact of these agents. We investigated whether killer cell immunoglobulin- like receptor (KIR) genes are related to response to anti-TNF-α therapy in patients with rheumatoid arthritis (RA). Sixty-four RA patients and 100 healthy controls were genotyped for 16 KIR genes and human leukocyte antigen-C (HLA-C) group 1/2 using polymerase chain reaction sequence-specific oligonucleotide probes (PCR-SSOP). Each patient received anti-TNF-α therapy (adalimumab, etanercept, or infliximab), and clinical responses were evaluated after 3 months using the disease activity score in 28 joints (DAS28). We investigated the correlations between the carriership of KIR genes, HLA-C group 1/2 genes, and clinical data with response to therapy. Patients responding to therapy showed a significantly higher frequency of KIR2DS2/KIR2DL2 (67.7% R vs. 33.3% NR; P = 0.012). A positive clinical outcome was associated with an activating KIR-HLA genotype; KIR2DS2+HLA-C group 1/2 homozygous. Inversely, nonresponse was associated with the relatively inhibitory KIR2DS2-HLA-C group 1/2 heterozygous genotype. The KIR and HLA-C genotype of an RA patient may provide predictive information for response to anti-TNF-α therapy.

Original languageEnglish
Pages (from-to)1647-1653
Number of pages7
JournalRheumatology International
Issue number6
Publication statusPublished - 2012 Jun 1



  • Anti-TNF-αlpha therapy
  • Genotype
  • Human leukocyte antigen-C
  • Killer immunoglobulin-like receptor
  • Natural killer cells
  • Responder
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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