This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Latrofa, F. Articles by McLachlan, S. M. Search for Related Content PubMed PubMed Citation Articles by Latrofa, F. Articles by McLachlan, S. M.

Human Monoclonal Thyroglobulin Autoantibodies: Epitopes and Immunoglobulin Genes

Autoimmune Disease Unit (F.L., B.R., S.M.M.), Cedars-Sinai Research Institute and the University of California, Los Angeles School of Medicine, Los Angeles, California 90048; and Department of Chemistry and Biochemistry (M.P.), University of California, Los Angeles, California 90095

Autoantibodies to thyroglobulin (TgAbs) are common markers of thyroid autoimmunity, but relatively few human monoclonal TgAbs have been described. From a panel of 64 human monoclonal TgAbs (isolated from a thyroid-disease derived combinatorial Ig gene library), we selected seven with unique genetic features for detailed characterization. These TgAbs preferentially recognize native (not denatured) Tg, like serum autoantibodies. Most have high affinities for Tg (dissociation constant 10^–10 to 10^–9 M). Their light (L) chain Ig genes are not unusual, but four of the five heavy (H) chain genes are new. Moreover, one H chain belongs to the small VH2 family, not previously reported for autoantibodies to Tg or thyroid peroxidase. The TgAbs inhibit the binding to Tg of the thyroid donor’s serum autoantibodies, indicating epitopic overlap. Competition analysis (surface plasmon resonance) shows that the TgAbs recognize overlapping epitopes in an immunodominant region on the Tg dimer (660 kDa). Two major and several minor epitopic regions were defined, each associated with a particular H + L chain combination. In conclusion, our TgAb panel provides novel information regarding the repertoire of H chain genes encoding human TgAbs as well as the relationship between the H chains and the epitopes recognized on this major thyroid autoantigen.

This article has been cited by other articles:

				F. Latrofa, D. Ricci, L. Grasso, P. Vitti, L. Masserini, F. Basolo, C. Ugolini, G. Mascia, A. Lucacchini, and A. Pinchera Characterization of Thyroglobulin Epitopes in Patients with Autoimmune and Non-Autoimmune Thyroid Diseases Using Recombinant Human Monoclonal Thyroglobulin Autoantibodies J. Clin. Endocrinol. Metab., February 1, 2008; 93(2): 591 - 596. [Abstract] [Full Text] [PDF]