A Peculiar Sequence Motif in the Alpha-1-Domain of the HLA-C Molecule in Psoriasis

Abstract

Background: Most immunogenetic studies restrict the location of the susceptibility gene for psoriasis to the HLA-C locus. Objective: The present study evaluates the amino acid sequences of the HLA-C binding groove associated with the disease in a restricted population of Italian descent: Pavia, Northern Italy. Method: Forty patients, affected by psoriasis, underwent genomic analysis of exons 2 and 3 of the HLA-C gene by means of the PCR-SSP technique. Results: The HLA-C*0602 gene frequency was significantly higher in patients with respect to 122 sex-, age- and ethnically matched controls (25 vs. 8.6%, χ² = 14.65, p = 0.000129). This frequency rose to 39.5% in patients with a family history positive for psoriasis. In particular, 4 amino acid substitutions were shown to be crucial for the predisposition to the disease, namely Ala 73 and Asn 77 (located in the C pocket of the antigen binding groove), Lys 80 in the F pocket and Asp 90 in the outer loop of the molecule. This peculiar motif, entirely located in the α₁-domain of the HLA-C molecule, was characteristic of psoriatic patients being present in 77.5% of the cases against the 50.82% of controls (χ² = 8.77; p = 0.0031). Homozygosity for the amino acids considered at these residues was found in 15% of patients and in 0% of controls (χ² = 20.74, p = 0.0000053). Conclusion: The most important results emerging from this study indicate that Ala 73, Asn 77, Lys 80 and Asp 90 together form a motif restricted to few pathogenic peptides to be studied in the near future.

The HLA-Cw6 Dilemma: Is It Really an Outcome Predictor in Psoriasis Patients under Biologic Therapy? A Monocentric Retrospective Analysis

“…Overall, 101 patients were collated; 23 (23%) were Cw6-positive, in line with the literature for Italian patients with psoriasis [ 16 ]. No significant associations were observed between age ( p = 0.28), gender ( p = 0.93), initial PASI score ( p = 0.37) or disease duration (0.12) and the treatment.…”

HLA-Cw6 and psoriasis

“…The worldwide HLA‐Cw6 allele frequency varies greatly and can range from 14·1% to 59·1%, whereas the percentage of patients with psoriasis carrying HLA‐Cw6 ranges from 10·5% to 77·2% (Table ) . Such wide ranges may be attributed to small sample sizes, ethnic diversity and differences in inclusion criteria.…”

Association between HLA-Cw*0602 polymorphism and psoriasis risk: a meta-analysis

“…According to the inclusion criteria, 18 studies with full-text were included in this meta-analysis (Rani et al, 1998;Gonzalez et al, 1999;Asumalahti et al, 2000;Brazzelli et al, 2000;Gudjonsson et al, 2003;Luszczek et al, 2003;Zhang et al, 2003;Sánchez et al, 2004;Martínez-Borra et al, 2003Holm et al, 2005a,b;Chang et al, 2004Chang et al, , 2005Chang et al, , 2006Płoski et al, 2006;Jobim et al, 2008;Fojtíková et al, 2009) and 127 studies were excluded. The flow chart for the study selection is summarized in Figure 1.…”