Open Access Research article

Contribution of KIR3DL1/3DS1 to ankylosing spondylitis in human leukocyte antigen-B27 Caucasian populations

Carlos Lopez-Larrea1*, Miguel Angel Blanco-Gelaz1, Juan Carlos Torre-Alonso2, Jacome Bruges Armas3, Beatriz Suarez-Alvarez1, Laura Pruneda1, Ana Rita Couto3, Segundo Gonzalez4, Antonio Lopez-Vázquez1 and Jesus Martinez-Borra1

Author Affiliations

1 Histocompatibility and Transplantation Unit, Hospital Universtario Central de Asturias, Celestino Villamil s/n. 33006 Oviedo, Asturias, Spain

2 Rheumatology Unit, Hospital Monte Naranco, Avda Dres Fernandez Vega 107. 33012 Oviedo, Asturias, Spain

3 Immunogenetic Service, Hospital de Santo Espirito de Angra do Heroismo, Vinha Brava. 9700 Angra do Heroismo, Azores, Portugal

4 Functional Biology Department, University of Oviedo, Avda Julian Claveria s/n. 33006 Oviedo, Asturias, Spain

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Arthritis Research & Therapy 2006, 8:R101  doi:10.1186/ar1988

Published: 28 June 2006

Abstract

Killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) loci are both highly polymorphic, and some HLA class I molecules bind and trigger cell-surface receptors specified by KIR genes. We examined whether the combination of KIR3DS1/3DL1 genes in concert with HLA-B27 genotypes is associated with susceptibility to ankylosing spondylitis (AS). Two HLA-B27-positive Caucasian populations were selected, one from Spain (71 patients and 105 controls) and another from the Azores (Portugal) (55 patients and 75 controls). All were typed for HLA-B and KIR (3DS1 and 3DL1) genes. Our results show that in addition to B27, the allele 3DS1 is associated with AS compared with B27 controls (p < 0.0001 and p < 0.003 in the Spanish population and Azoreans, respectively). We also observed that the association of KIR3DS1 to AS was found in combination with HLA-B alleles carrying Bw4-I80 in trans position in the Spanish population (30.9% in AS versus 15.2% in B27 controls, p = 0.02, odds ratio (OR) = 2.49) and in Azoreans (27.2% in AS versus 8.7% in B27 controls, p = 0.01, OR = 4.4 in Azoreans). On the other hand, 3DL1 was decreased in patients compared with B27 controls (p < 0.0001 in the Spanish population and p < 0.003 in Azoreans). The presence of this allele in combination with Bw4-I80 had a protective effect against the development of AS in the Spanish population (19.7% in AS, 35.2% in B27 controls; p = 0.03, OR = 0.45). The presence of KIR3DS1 or KIR3DL1 in combination with HLA-B*27s/HLA-B Bw4-I80 genotypes may modulate the development of AS. The susceptibility to AS could be determined by the overall balance of activating and inhibitory composite KIR-HLA genotypes.