Immunogenetic associations of scleroderma-related antinuclear antibodies.
Patients selected for the presence of scleroderma-related antibodies (anti-DNA-topoisomerase I [anti-topo I; n = 43], anticentromere antibody [ACA; n = 63], or anti-Pm-Scl [n = 12]) were studied for class I and class II major histocompatibility complex antigens, as well as for Gm and Km allotypes. Anti-topo I was associated with HLA-DR5 (70% of patients versus 30.6% of controls; Pcorr = 0.0018, relative risk [RR] = 5.3). All patients with anti-Pm-Scl were positive for HLA-DR3 (versus 23.5% of controls; Pcorr less than 0.001); 6 of these patients were DR3/4 heterozygous (50% versus 3.5% of controls; Pcorr less than 0.001, RR = 27.3). Patients with ACA were frequently positive for HLA-DR1, DR4, or DRw8, with 73.7% demonstrating at least 1 of these alleles (versus 41.2% of controls; Pcorr = 0.0152, RR = 4.0). This group of ACA-positive patients who had DR1, DR4, and/or DRw8 consisted mainly of a subgroup of patients with rheumatoid arthritis. We conclude that different class II major histocompatibility complex antigens influence the formation of anti-topo I and anti-Pm-Scl. Important clinical differences between these patient groups and the immunogenetic heterogeneity support the notion of different antibody-defined scleroderma subsets.
Genth
E
E
Rheumaforschungsinstitut, Rheumaklinik Aachen, FRG.
Mierau
R
R
Genetzky
P
P
von Mühlen
C A
CA
Kaufmann
S
S
von Wilmowsky
H
H
Meurer
M
M
Krieg
T
T
Pollmann
H J
HJ
Hartl
P W
PW
D000974:Antibodies, Antinuclear / Q000235:genetics / Q000276:immunology*; D006680:HLA Antigens / Q000032:analysis / Q000145:classification; D006684:HLA-DR Antigens / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D007125:Immunogenetics; D012595:Scleroderma, Systemic / Q000276:immunology*
D000974:Antibodies, Antinuclear; D006680:HLA Antigens; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I