Polymorphisms of KIRs gene and HLA-C alleles in patients with ankylosing spondylitis: possible association with susceptibility to the disease.
BACKGROUND
An emerging body of evidence is accumulating to suggest that killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands contribute to the pathogenesis of diverse kinds of autoimmune diseases. However, the functional effects of their polymorphism remain largely unknown to date. Thus, the present study was undertaken to determine the association of the polymorphisms KIRs gene and HLA-C alleles with the susceptibility to ankylosing spondylitis (AS) by means of polymerase chain reaction/sequence-specific primers for genotyping KIRs from genomic DNA of 119 patients with AS together with 128 healthy donors as a control group.


CONCLUSIONS
We found that the frequencies of KIR3DS1 and KIR2DL5 were statistically significantly higher in the patient group than those in the control group (P = 0.016 and P = 0.003, respectively). Meanwhile, the percentage of patients, who were carrying two or more of the activating KIRs, was higher than that of control group. With respect to HLA-C alleles, individuals with AS showed an increased frequency of HLA-Cw02. If HLA-C was divided into group 1 or group 2 based on whether there was an asparagine or lysine present at position 80 of the alpha-chain, HLA-C group 2 was more common in subjects with AS compared to control subjects. The genotype 2DS1+/HLA-C lys(80)+ was more common in subjects with AS. Moreover, the CD69 expression, a NK activation marker, remarkably increased in patient with AS.


CONCLUSIONS
In conclusions, this study suggests that KIR3DS1 may severe as AS susceptive genes to trigger continuous injury of arthrosis. The imbalance of activating and inhibitory KIR as well as HLA-C group 1 and group 2 may be the key factor, which influences the pathogenesis of AS. Moreover, KIR2DS1 might associate with the susceptibility of AS by influencing NK cell activity once group 2 HLA-C ligands are present.
Jiao
Yu-Lian
YL
Central Laboratory, Shandong Provincial Hospital, Shandong University, Jinan 250021, People's Republic of China.
Ma
Chun-Yan
CY
Wang
Lai-Cheng
LC
Cui
Bin
B
Zhang
Jie
J
You
Li
L
Chen
Zi-Jiang
ZJ
Li
Jian-Feng
JF
Zhao
Yue-Ran
YR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D015236:HLA-C Antigens / Q000235:genetics*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D054340:Receptors, KIR / Q000235:genetics*; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000276:immunology
D015236:HLA-C Antigens; D054340:Receptors, KIR