Psoriasis is a multifactorial disease with a strong genetic background. It associates strongly to HLA-Cw*0602.
HLA-C interacts with killer
immunoglobulin-like
receptors (KIR) on natural killer (NK) and some natural killer-T (NKT) cells. KIR's function is triggered by specific binding to HLA
ligands, which depends on the
amino acid 80 of the MHC class I alpha-chain. This permits classifying all
HLA-C alleles into two functional groups:
asparagine (N80) or
lysine (K80) carrying alleles.
Psoriasis patients recruited at disease onset were categorized as guttate, vulgaris without
arthropathy and vulgaris with
arthropathy plus skin lesions. Patients and carefully matched controls were genotyped for position 80 of
HLA-C and for KIR. Based on possible HLA/KIR combinations, individuals were classified according to expected NK/NKT cell responses: balanced (B), excess inhibition (EI), excess activation (EA), or undetermined (U).
HLA-Cw6 and position 80 genotyping associated strongly to disease, whereas KIR2DS1 associated weakly. Individuals of the U and EI classes were more common among guttate
psoriasis patients, which related to HLA-Cw*0602 status. These results suggest that different levels for NK/NKT cell activation thresholds, not only reduction, contribute to immune deregulation in
psoriasis. In the guttate phenotype, balanced
HLA-C/KIR interactions might be altered by the presence of concomitant
streptococcal infections.