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Comparative Study
. 2012 Jun;32(6):1647-53.
doi: 10.1007/s00296-011-1838-6. Epub 2011 Mar 4.

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  1 , Daniel Berrar, Gary Wright, Clare Mathews, Paula Gilmore, Rodat T Cunningham, Anthony J Bjourson
Affiliations
Comparative Study

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 et al. Rheumatol Int. 2012 Jun.

Abstract

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, non-response 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.

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Figures

Fig. 1
Fig. 1
Number of responders (white) and non-responders (black) in the groups I to IV. Groups range from most activating to most inhibiting from groups I to IV, respectively. Patients included in group I are KIR2DS2 positive and HLA-C group 1/2 homozygous (C1/C1 or C2/C2). Group II patients are KIR2DS2 positive and HLA-C group 1/2 heterozygous (C1/C2). Group III patients are KIR2DS2 negative and HLA-C group 1/2 homozygous. Group IV patients are KIR2DS2 negative and HLA-C group 1/2 hetrozygous
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References

    1. Suto Y, Maenaka K, Yabe T, Hirai M, Tokunaga K, Tadok K, et al. Chromosomal localisation of the human natural killer cell class I receptor family genes to 19q13.4 by fluorescence in situ hybridisation. Genomics. 1996;35:270–272. doi: 10.1006/geno.1996.0355. - DOI - PubMed
    1. Winter CC, Gumperz JE, Parham P, Long EO, Wagtmann N. Direct binding and functional transfer of NK cell inhibitory receptors reveal novel patterns of HLA-C allotype recognition. J Immunol. 1998;161:571–577. - PubMed
    1. Valéz-Gómez M, Reyburn HT, Erskine RA, Stominger J. Differential binding to HLA-C of p50-activating and p58-inhibitory natural killer cell receptors. Proc Natl Acad Sci USA. 1998;95:14326–14331. doi: 10.1073/pnas.95.24.14326. - DOI - PMC - PubMed
    1. Carrington M, Martin MP. The impact of variation at the KIR gene cluster on human disease. Curr Top Microbiol Immmunol. 2006;298:225–257. doi: 10.1007/3-540-27743-9_12. - DOI - PubMed
    1. Martin MP, Gao X, Lee JH, Nelson GW, Detels R, Goedert JJ, et al. Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Nature Genet. 2002;31:429–434. - PubMed

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