TY - JOUR
T1 - Killer immunoglobulin-like receptor and human leukocyte antigen-C genotypes in rheumatoid arthritis primary responders and non-responders to anti-TNF-α therapy
AU - McGeough, Cathy M.
AU - Berrar, Daniel
AU - Wright, Gary
AU - Mathews, Clare
AU - Gilmore, Paula
AU - Cunningham, Rodat T.
AU - Bjourson, Anthony J.
N1 - Funding Information:
Acknowledgments This work was supported by a Co-operative Award in Science & Technology (CAST) grant from the Department of Employment & Learning, Northern Ireland.
Funding Information:
Conflict of interest A patent application (US2010323358) for ‘‘the use of KIR genes for predicting response to anti-TNF-α therapy’’ was deposited by the University of Ulster (CM McGeough, AJ Bjourson, Daniel Berrar). GW and CM have received honoraria and/or grant support from Abbott, Schering-Plough and Wyeth. There has been no financing of the current manuscript by any of the above. RC and PG have no competing interests.
PY - 2012/6
Y1 - 2012/6
N2 - 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.
AB - 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.
KW - Anti-TNF-αlpha therapy
KW - Genotype
KW - Human leukocyte antigen-C
KW - Killer immunoglobulin-like receptor
KW - Natural killer cells
KW - Responder
KW - Rheumatoid arthritis
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U2 - 10.1007/s00296-011-1838-6
DO - 10.1007/s00296-011-1838-6
M3 - Article
C2 - 21373785
AN - SCOPUS:84863880925
VL - 32
SP - 1647
EP - 1653
JO - Rheumatology International
JF - Rheumatology International
SN - 0172-8172
IS - 6
ER -