Thymus function in drug-induced lupus.
Autoimmunity develops when a lupus-inducing drug is introduced into the thymus of normal mice, but the relevance of this model to the human disorder is unclear in part because it is widely assumed that the thymus is non-functional in the adult. We compared thymus function in 10 patients with symptomatic procainamide-induced lupus to that in 13 asymptomatic patients who only developed drug-induced autoantibodies. T cell output from the thymus was quantified using a competitive polymerase chain reaction that detects T cell receptor DNA excision circles in peripheral blood lymphocytes. Despite the advanced age of the patient population under study, newly generated T cells were detected in all subjects. Although there was no overall quantitative difference between the symptomatic and asymptomatic patients, we found a positive correlation between the level of T cell receptor excision circles in peripheral lymphocytes and serum IgG anti-chromatin antibody activity in patients with drug-induced lupus. The association between autoantibodies and nascent peripheral T cells supports the requirement for T cells in autoantibody production. Our observations are consistent with findings in mice in which autoreactive T cells derived from drug-induced abnormalities in T cell development in the thymus.
Rubin
R L
RL
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA. rrubin@liai.org
Salomon
D R
DR
Guerrero
R S
RS
D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D001323:Autoantibodies / Q000097:blood; D001483:Base Sequence; D002843:Chromatin / Q000276:immunology; D005260:Female; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor / Q000235:genetics / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007074:Immunoglobulin G / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011342:Procainamide / Q000009:adverse effects; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*
D000889:Anti-Arrhythmia Agents; D001323:Autoantibodies; D002843:Chromatin; D007074:Immunoglobulin G; D011342:Procainamide