Gene for the activating natural killer cell receptor, KIR2DS1, is associated with susceptibility to psoriasis vulgaris.
Psoriasis vulgaris, particularly its juvenile form, is strongly associated with the HLA-Cw*06 allele encoding the HLA-Cw6 molecule. This molecule is recognized by the inhibitory receptor KIR2DL1 and the activatory receptor KIR2DS1, which are expressed on natural killer cells and subpopulations of T lymphocytes. Humans differ by the presence or absence of particular KIR genes. We hypothesized that either activatory KIR2DS1 or inhibitory KIR2DL1 gene frequencies might be different in psoriatic patients from a control population. Therefore, we compared the frequencies of KIR2D inhibitory (L) and activatory (S) genes in 116 psoriasis vulgaris patients and in 123 healthy controls. Fourteen novel gene combinations were found. KIR2DS1 was present in 85% of the patients, but only in 51% of the controls (corrected p [pc] < 0.0009). Similarly, HLA-Cw*06 was much more frequent in patients (77%) than in controls (17%; pc < 0.00002). Statistical analysis suggests that, although the contribution of these two factors to psoriasis is partially independent, they interact nevertheless. This result strongly speaks for a role of KIR2DS1 on recognition of HLA-Cw6 in susceptibility to psoriasis.
Laboratory of Immunogenetics, Department of Clinical Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
Wioleta
W
Łuszczek
Maria
M
Mańczak
Maria
M
Cisło
Piotr
P
Nockowski
Andrzej
A
Wiśniewski
Monika
M
Jasek
Piotr
P
Kuśnierczyk
D000328:Adult; D017668:Age of Onset; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D003627:Data Interpretation, Statistical; D004587:Electrophoresis, Agar Gel; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011044:Poland; D016133:Polymerase Chain Reaction; D011565:Psoriasis / Q000175:diagnosis / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics* / Q000276:immunology; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1
D015236:HLA-C Antigens; C528994:HLA-C*06 antigen; C093100:KIR2DL1 protein, human; C496212:KIR2DS1 protein, human; C433932:KIR2DS2 protein, human; C473953:KIR2DS4 protein, human; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D004247:DNA