CLONING AND ANALYSIS OF IGM ANTITHYROGLOBULIN AUTOANTIBODIES FROM PATIENTS WITH HASHIMOTOS-THYROIDITIS

Hashimoto's thyroiditis is an autoimmune disease in which autoantibodi es reactive to a number of thyroid antigens are made. In order to inve stigate the autoantibody repertoire in this disease, B cells from four patients with Hashimoto's thyroiditis were immortalised and, after li miting dilution, screened for reactivity to thyroid antigens. After a second limiting dilution, one anti-thyroglobulin IgM-secreting clone f rom three patients, and four clones from one patient, were analysed. T he Ig heavy and light chain genes from each done were amplified using the polymerase chain reaction and sequenced. The resulting heavy and l ight chain sequences were heterogeneous, although the four clones from one patient and the clone from a second patient shared a germline V-H sequence. Ah antibodies had similar functional affinity, comparable t o serum IgG from Hashimoto's patients. The cross-reactivity of the ant ibodies was analysed against bovine and rat thyroglobulin, histones, c ardiolipin and human skeletal muscle. The antibodies were polyreactive , indicating that they are probably natural autoantibodies of unknown pathogenic significance.