Association of killer cell immunoglobulin-like receptor genotypes with microscopic polyangiitis.
OBJECTIVE
Genetic background and infection have been implicated in the etiology of microscopic polyangiitis (MPA). Killer cell immunoglobulin-like receptors (KIRs) are a diverse family of activating and inhibitory receptors expressed on natural killer (NK) cells and T cells, the genes of which show extreme polymorphism. Some KIRs bind to HLA class I subgroups, and genetic interactions between KIR genes and their ligand HLA have been shown to be associated with several autoimmune and viral diseases. In this study, we examined possible associations of the presence or absence of KIR loci with a genetic predisposition to MPA.


METHODS
The presence or absence of 14 KIR loci was determined in 57 myeloperoxidase antineutrophil cytoplasmic antibody-positive Japanese subjects (43 patients with MPA and 239 healthy controls).


RESULTS
The carrier frequency of activating KIR2DS3 was significantly decreased among patients with MPA compared with healthy controls (4.7% versus 16.7%; P = 0.038, odds ratio [OR] 0.24, 95% confidence interval [95% CI] 0.06-0.94). When KIRs were analyzed in combination with their HLA ligands, the proportion of individuals carrying inhibitory KIR3DL1 and HLA-Bw4 but not activating receptor KIR3DS1, a combination presumed to be the most inhibitory of all KIR3DS1/3DL1/HLA-B combinations, was significantly increased in the MPA group compared with the control group (46.5% versus 27.0%; P = 0.014, OR 2.35, 95% CI 1.18-4.70). Furthermore, when subjects were classified according to KIR3DL1/3DS1/HLA-B and KIR2DL1/ HLA-C combinations, an increasing trend toward susceptibility was observed as combinations became more inhibitory.


CONCLUSIONS
The decreased activation potential of NK and/or T cells associated with KIR/HLA genotypes may predispose to MPA, possibly through insufficient resistance against infections.
Miyashita
Risa
R
University of Tokyo, Hongo, Tokyo, Japan.
Tsuchiya
Naoyuki
N
Yabe
Toshio
T
Kobayashi
Shigeto
S
Hashimoto
Hiroshi
H
Ozaki
Shoichi
S
Tokunaga
Katsushi
K
D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011971:Receptors, Immunologic / Q000235:genetics*; D014657:Vasculitis / Q000235:genetics*
D011971:Receptors, Immunologic