Contribution of KIR3DL1/3DS1 to ankylosing spondylitis in human leukocyte antigen-B27 Caucasian populations.
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.
Lopez-Larrea
Carlos
C
Histocompatibility and Transplantation Unit, Hospital Universtario Central de Asturias, Celestino Villamil s/n, 33006 Oviedo, Asturias, Spain. inmuno@hca.es
Blanco-Gelaz
Miguel Angel
MA
Torre-Alonso
Juan Carlos
JC
Bruges Armas
Jacome
J
Suarez-Alvarez
Beatriz
B
Pruneda
Laura
L
Couto
Ana Rita
AR
Gonzalez
Segundo
S
Lopez-Vázquez
Antonio
A
Martinez-Borra
Jesus
J
D000483:Alleles; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics; D015796:HLA-B27 Antigen / Q000097:blood*; D006801:Humans; D011174:Portugal; D011971:Receptors, Immunologic / Q000235:genetics*; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D054349:Receptors, KIR3DS1; D013030:Spain; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000276:immunology*; D044465:White People / Q000235:genetics*
D015235:HLA-B Antigens; D015796:HLA-B27 Antigen; C515083:KIR3DL1 protein, human; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D054349:Receptors, KIR3DS1