Association of HLA-DR5 (DR11) with systemic sclerosis (scleroderma) in Mexican patients

To study the association between Major Histocompatibility Complex (MHC) haplotypes and systemic sclerosis (SSc) in Mexican mestizo patients.

Class I, II and III MHC antigens were determined in 41 Mexican mestizo patients with SSc, 113 of their first degree relatives, and 85 ethnically matched controls. The significance of differences between patients and controls was tested by chi-square analysis with Yates' correction.

Frequencies of HLA-DR5 and HLA-DRw52 were found to be higher in SSc patients compared to ethnically matched healthy controls (p = 0.007, RR = 3.31; 95% confidence interval: 1.3-8.3 and p = 0.04, RR = 2.4; 95% confidence interval: 1.0-5.7, respectively). Sequence-specific oligotyping in DR5 positive individuals showed that 10 out of 41 patients had the DRB1*1104 subtype (24.3%) as compared to only 6 of the 85 healthy controls (7.0%) (p = 0.01, RR = 4.25). Subdividing patients according to their clinical features showed a significant increase of HLA-DR5 in diffuse (p = 0.013, RR = 3.89, 95% confidence interval: 1.27-12.0) and limited scleroderma (p = 0.0008), but not in the CREST syndrome. Segregation analysis obtained from the families showed that in the patients, DR5 was mostly part of the [HLAB35;DR5] haplotype as opposed to healthy controls.

These data support the role of DR5 (DRB1*1104) in the genetic susceptibility to develop scleroderma in Mexican patients and also sustain the notion of genetically determined clinical subgroups of SSc.