Immunogenetic associations of scleroderma‐related antinuclear antibodies

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Abstract
Patients selected for the presence of sclerodermarelated antibodies (anti‐DNA‐topoisomerase I [antitopo 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 < 0.001); 6 of these patients were DR3/4 heterozygous (50% versus 3.5% of controls; Pcorr < 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.