Analysis of IgG subclasses of human antitopoisomerase I autoantibodies suggests chronic B cell stimulation.
Antitopoisomerase I autoantibodies are highly specific of scleroderma and are mainly IgG. The present study was designed to evaluate the prevalence of each IgG antitopoisomerase I subclass. An ELISA for the detection of IgG antitopoisomerase I subclasses was standardized and used to study the antibodies from 49 antitopoisomerase I-positive patients identified from a total of 541 patients. Correlations and multivariate analysis were performed to determine the frequency of associations between the IgG antitopoisomerase I subclasses. All IgG antitopoisomerase I subclasses were found. Twelve patients (24.5%) had all four IgG antitopoisomerase I subclasses, 13 (26.5%) had three, 16 (32.7%) had two, and 7 (14.3%) had only one antitopoisomerase I subclass. The presence of all four IgG antitopoisomerase I subclasses suggests that this specific B-cell is the target of multiple activation pathways which indicate that there is a complex T-cell-cytokine-driven process. Together with the absence of other autoantibodies in these sera, our results support the concept of a multiple but highly selected and chronic B-cell activation in scleroderma patients with antitopoisomerase I.
Vázquez-Abad
D
D
Department of Medicine, University of Connecticut School of Medicine, Farmington 06030, USA. vazquez@panda.uchc.edu
Monteón
V
V
Senécal
J L
JL
Walsh
S
S
Rothfield
N
N
D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood / Q000145:classification*; D001402:B-Lymphocytes / Q000276:immunology*; D004264:DNA Topoisomerases, Type I / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000592:standards / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio
D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D004264:DNA Topoisomerases, Type I