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Int Rev Immunol. 2000;19(6):587-618.

Autoimmune response to the thyroid in humans: thyroid peroxidase--the common autoantigenic denominator.

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Autoimmune Disease Unit, Cedars-Sinai Research Institute and School of Medicine, University of California, Los Angeles School of Medicine, USA.


Autoimmunity to thyroid peroxidase (TPO), manifest as high affinity IgG class autoantibodies, is the common denominator of human thyroid autoimmunity, encompassing patients with overt hyper- or hypothyroidism as well as euthyroid individuals with subclinical disease. The identification and cloning of TPO (the "thyroid microsomal antigen") provided the critical tool for analyzing B and T cell reactivity to this major thyroid autoantigen. In particular, the availability of immunoreactive TPO permitted the isolation of essentially the entire repertoire of human monoclonal antibodies, a feat unparalled in an organ-specific autoimmune disease. These recombinant autoantibodies (expressed as Fab) provide insight into the genes encoding their H and L chains as well as the conformational epitopes on TPO with which serum autoantibodies interact. Analyses of TPO autoantibody epitopic "fingerprints" indicate a lack of epitope spreading as well as a genetic basis for their inheritance. Limited data are available for the responses and cytokine profiles of T cells to endogenously processed TPO. Moreover, the role of thyroid cells in initiating the autoimmune response to TPO, and of B cells in expanding and/or modulating the response of sensitized T cells, has yet to be established. Finally, because autoantibody (and likely T cell) responses to TPO parallel those to TSH receptor and thyroglobulin, manipulation of T and B cell responses to TPO may provide the basis for the development of immunospecific therapy for autoimmune thyroid disease in general.

[Indexed for MEDLINE]

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