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, 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 language | English |
|---|---|
| Pages (from-to) | 1647-1653 |
| Number of pages | 7 |
| Journal | Rheumatology International |
| Volume | 32 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2012 Jun |
| Externally published | Yes |
Keywords
- 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
- Immunology and Allergy
Cite this
Killer immunoglobulin-like receptor and human leukocyte antigen-C genotypes in rheumatoid arthritis primary responders and non-responders to anti-TNF-α therapy. / McGeough, Cathy M.; Berrar, Daniel; Wright, Gary; Mathews, Clare; Gilmore, Paula; Cunningham, Rodat T.; Bjourson, Anthony J.
In: Rheumatology International, Vol. 32, No. 6, 06.2012, p. 1647-1653.Research output: Contribution to journal › Article
}
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.
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
UR - http://www.scopus.com/inward/record.url?scp=84863880925&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863880925&partnerID=8YFLogxK
U2 - 10.1007/s00296-011-1838-6
DO - 10.1007/s00296-011-1838-6
M3 - Article
VL - 32
SP - 1647
EP - 1653
JO - Rheumatology International
JF - Rheumatology International
SN - 0172-8172
IS - 6
ER -