A study of KIR genes and HLA-C in Vogt-Koyanagi-Harada disease in Saudi Arabia.
OBJECTIVE
Vogt-Koyanagi-Harada (VKH) disease is a serious ocular inflammatory autoimmune insult directed against antigens associated with melanocytes. The repertoire of killer cell immunoglobulin-like receptors (KIRs) is known to play a significant role in the pathogenesis of various autoimmune disorders. Accordingly, we sought to determine the incidence of KIR genes and KIR ligand (Human leukocytes antigen [HLA-C]) interaction in a cohort of Saudi VKH patients and to compare the findings to normal controls.


METHODS
A total of 30 patients with VKH and 125 control subjects were included. PCR using sequence-specific oligonucleotide primers were employed to determine the genotype of the KIR genes and HLA-C alleles.


RESULTS
The frequency of KIR2DS3 was significantly higher in the VKH patients than in the control group (p=0.048). Two unique genotypes; VKHN*1 and VKHN*2 were observed in the VKH patients and not in normal controls. In addition, the majority of the VKH patients (82%) in this study carry Bx genotypes that encode 2-5 activating KIR receptors. The genotype Bx5 was found to be positively associated with the VKH patients (p=0.053). Significantly higher homozygosity of HLA-C2 was observed in the VKH patients than in controls (p=0.005). Furthermore, HLA-C alleles-Cw*14 and Cw*17 were significantly prevalent in the VKH patients (p=0.037 and p=0.0001, respectively), whereas, Cw*15 significantly increased in the control group (p=0.0205). Among potential KIR-HLA interactions, we observed KIR2DL2/2DL3+HLA-C1 to be higher in the control subjects compared with the VKH patients (p=0.018).


CONCLUSIONS
Our findings indicated that KIR2DS3 and HLA-class I alleles (-Cw*14 and -Cw*17) may play a role in the pathogenesis of VKH disease. Additionally, the predominance of KIR2DL2/2DL3+HLA-C1 in the controls may imply that this KIR-ligand interaction could possibly play a role in the prevention of VKH disease, or could decrease its severity. These observations may contribute to our understanding of the pathogenesis of VKH and other autoimmune diseases.
Histocompatibility and Immunogenetics Research Unit, Stem Cell Therapy Program, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Atia
A
Sheereen
Ameera
A
Gaafar
Alia
A
Iqneibi
Abdelmoneim
A
Eldali
Khalid F
KF
Tabbara
Chaker
C
Adra
Khaled
K
Al-Hussein
D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D005123:Eye / Q000378:metabolism* / Q000473:pathology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D058889:Molecular Typing; D016133:Polymerase Chain Reaction; D054340:Receptors, KIR / Q000235:genetics*; D012529:Saudi Arabia; D014607:Uveomeningoencephalitic Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D015236:HLA-C Antigens; D054340:Receptors, KIR