Association of the KIR3DS1*013 and KIR3DL1*004 Alleles With Susceptibility to Ankylosing Spondylitis

Diaz-Pena, Roberto; Ramon Vidal-Castineira, Jose; Alonso-Arias, Rebeca; Suarez-Alvarez, Beatriz; Luis Vicario, Jose; Solana, Rafael; Collantes, Eduardo; Lopez-Vazquez, Antonio; Martinez-Borra, Jesus; Lopez-Larrea, Carlos

Abstract

Objective. The killer cell immunoglobulin-like receptors (KIRs) form a group of regulatory molecules that specifically recognize HLA class I molecules. The aim of this study was to analyze the possible contribution of the KIR3DL1 and KIR3DS1 alleles, in addition to HLA-B27, in the susceptibility to ankylosing spondylitis (AS) in a population of individuals from Spain. Methods. We genotyped the KIR3DS1 and KIR3DL1 alleles in 2 cohorts of patients with AS and healthy control subjects. In total, 270 patients with AS and 435 healthy, HLA-B27-positive matched control subjects from Spain were enrolled. The KIR3DS1 and KIR3DL1 alleles were genotyped by sequence-specific oligonucleotide probe-polymerase chain reaction, and their association with AS was analyzed. All individuals were typed for HLA-B. Results. The KIR3DS1*013 allele was solely responsible for the increased frequency of the activator receptor KIR3DS1 in patients with AS compared with healthy HLA-B27-positive control subjects (35.7% versus 22.6% [P = 10(-6)], odds ratio 1.90, 95% confidence interval 1.50-2.40). The increased frequency of the KIR3DS1*013 allele in patients with AS was independent of the presence or absence of the HLA-Bw4I80 epitope. Moreover, the null allele KIR3DL1*004 was a unique inhibitory KIR3DL1 allele that showed a negative association with AS in the presence of HLA-Bw4I80. Conclusion. The increased frequency of the KIR3DS1*013 allele in patients with AS is clearly independent of the presence of the HLA-Bw4I80 epitope, whereas the presence of inhibitory allotypes such as KIR3DL1*004 demonstrated a negative association in patients with AS in the presence of HLA-Bw4I80. As a consequence, the influence of KIR genotypes on AS susceptibility would be mediated by a general imbalance between protective/inhibitory and risk/activating allotypes.

Más información

Título según WOS: ID WOS:000279432300010 Not found in local WOS DB
Título de la Revista: ARTHRITIS AND RHEUMATISM
Volumen: 62
Número: 4
Editorial: Wiley
Fecha de publicación: 2010
Página de inicio: 1000
Página final: 1006
DOI:

10.1002/art.27332

Notas: ISI