Association of human leukocyte antigen class II genes with autoantibody profiles, but not with disease susceptibility in Japanese patients with systemic sclerosis
M. Kuwana et al., Association of human leukocyte antigen class II genes with autoantibody profiles, but not with disease susceptibility in Japanese patients with systemic sclerosis, INTERN MED, 38(4), 1999, pp. 336-344
Object: To examine the role of human leukocyte antigen (HLA) class II genes
in the development of systemic sclerosis (SSc) as well as in the clinical
and serologic expression of SSc in patients,
Methods: HLA-DRB1, DRB3, DRB4, DQB1, and DPB1 alleles were determined by ge
notyping; and serum antinuclear antibodies were identified using indirect i
mmunofluorescence, double immunodiffusion and immunoprecipitation,
Patients: One hundred and five Japanese patients with SSc and 104 race-matc
hed healthy controls.
Results: Frequencies of DRB1 and DQB1 alleles were not different between SS
c patients and healthy controls, while DPB1*0901 was marginally increased i
n SSc patients, In contrast, SSc-related autoantibodies were closely associ
ated with the clinical features. HLA class II genes were detected as follow
s: anti-DNA topoisomerase I antibody with diffuse cutaneous involvement, pu
lmonary fibrosis, and DRB1*1502-DQB1*0601-DPB1*0901; anti-U1RNP antibody wi
th overlapping features of lupus and/or myositis and DRB1*0401/*0802-DQB1*0
302; and anticentromere antibody with limited cutaneous involvement and DRB
1*0101-DQB1*0501-DPB1*0402. In the analysis of the association of HLA class
II and the clinical features in SSc patients significant differences were
obtained only for the increased frequencies of arthritis and rheumatoid fac
tor in patients with DRB1*0405 compared to those without.
Conclusion: HLA class II genes strongly influence the production of SSc-rel
ated autoantibodies rather than the development of SSc, In addition, SSc is
a composite disease of distinctive subsets defined by serum autoantibodies
, which have specific clinical and HLA class II associations.