Objective. To clarify the contribution of HLA-DR genes to the suscepti
bility to progressive systemic sclerosis (PSS). Methods. HLA-DR typing
was carried out in 36 Japanese patients with PSS, 42 with systemic lu
pus erythematosus and 104 healthy subjects by polymerase chain reactio
n (PCR) method using specific primers and by PCR-SSCP (single-standard
DNA conformation polymorphism) method. Results. A haplotype DRB11502
-DRB50102 was significantly increased in PSS (50.0%, p < 0.00004, pc
< 0.001), especially in antitopoisomerase I antibody (a-Scl-70) positi
ve patients (62.5%, p < 0.00003, pc < 0.001) and PSS with diffuse scle
roderma (75.0%, p < 0.00001, pc < 0.0001). In addition, DRB10802 was
also increased in DRB11502 negative patients with a-Scl-70, (50.0%, p
= 0.033, pc = not significant) and in DRB11502 negative patients wit
h diffuse scleroderma (75.0%, p = 0.008, pc = not significant). Thus,
81.3% of a-Scl-70 positive patients, and 93.8% of patients with PSS wi
th diffuse scleroderma showed either HLA-DRB11502 or 0802. Conclusion
s. Our observations show the extreme difference of genetic background
of a-Scl-70 positive PSS, with regard to HLA-DR, between Japanese and
other ethnic groups including Caucasian and American black persons. Th
e increase in DRB11502-DRB5*0102 haplotype supported the hypothesis o
f Reveille, et al that uncharged polar amino acid residue at position
30 of HLA-DQB1 allele was important for a-Scl-70 positive PSS because
close association of the haplotype with DQB10601 was well established
in Japanese; listed as a hypothetical candidate of PSS susceptible DQ
B1 allele. DRB10802 were also associated with hypothetical candidates
of DQ alleles. Furthermore, the sharing of the particular amino acid
sequence: valine(38) and phenylalanine(67)-lysine(68)-glutamic acid(69
)-asparic acid(70)-arginine(71), by DRB50102, DRB1*0802 and DR11 (ass
ociated with Caucasian PSS) also suggests a contribution of the sequen
ce in HLA-DR molecules to the pathogenesis of PSS according to the sha
red epitope hypothesis.