Inhibitory killer cell immunoglobulin-like receptor KIR3DL1 in combination with HLA-B Bw4iso protect against ankylosing spondylitis.
BACKGROUND
The HLA class I molecules serve as ligands for both T cell receptors and killer cell immunoglobulin-like receptors (KIRs).


OBJECTIVE
We investigated the HLA-C and HLA-Bw4 alleles as well as KIRs expression on CD56 positive lymphocytes to evaluate whether these genes and molecules could influence Ankylosing Spondylitis (AS) susceptibility, alone or in combination.


METHODS
We typed 40 AS patients and 40 normal controls for HLA-C asn⁸⁰ (group 1) and HLA-C lys⁸⁰ (group 2), HLA-B Bw4(thero), HLA-B Bw4(iso) and HLA-A Bw4 alleles by PCR-SSP method. We also assessed the expression of KIR2DL1/2DS1, KIR2DL2/2DL3, KIR3DL1 and KIR2DS4 by flow cytometry. The Pearson chi-square or Fisher exact test was performed for statistical analysis.


RESULTS
The frequency of HLA-B Bw4(iso) but not HLA-B Bw4(thero) and HLA-A Bw4, ligand for the inhibitory KIR3DL1, was significantly reduced in AS patients as compared with controls (p<0.01). No significant differences were observed in gene carrier frequencies of HLA-C group 1 and 2 between AS and controls. Although no differences were found in the expression of KIR receptors between AS and normal subjects, we found that expression of KIR3DL1 in the presence of HLA Bw4-B(iso) gene was reduced in patients with AS compared to healthy controls (p<0.009).


CONCLUSIONS
We conclude that HLA-B Bw4(iso), the ligand of inhibitory KIR3DL1, with and without the expression of KIR3DL1 might be involved in protection against AS. Our results suggest that besides the HLA and KIR genotype, expression levels of KIRs may be involved in the pathogenesis of AS disease.
Mousavi
Tahereh
T
Department of Immunology, Iran University of Medical Sciences, Tehran, Iran. yasaha@iums.ac.ir
Poormoghim
Hadi
H
Moradi
Maziar
M
Tajik
Nader
N
Shahsavar
Farhad
F
Asadifar
Behnam
B
D019002:CD56 Antigen / Q000096:biosynthesis; D015536:Down-Regulation / Q000276:immunology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015235:HLA-B Antigens / Q000235:genetics*; D015236:HLA-C Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D054340:Receptors, KIR / Q000235:genetics; D054342:Receptors, KIR2DL1 / Q000235:genetics; D054343:Receptors, KIR2DL2 / Q000235:genetics; D054341:Receptors, KIR3DL1 / Q000235:genetics / Q000378:metabolism*; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology
D019002:CD56 Antigen; D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; D015236:HLA-C Antigens; C093100:KIR2DL1 protein, human; C515077:KIR2DL2 protein, human; C473953:KIR2DS4 protein, human; C515083:KIR3DL1 protein, human; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054343:Receptors, KIR2DL2; D054341:Receptors, KIR3DL1