Autoimmune response to the thyroid in humans: thyroid peroxidase--the common autoantigenic denominator.
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.
McLachlan
S M
SM
Autoimmune Disease Unit, Cedars-Sinai Research Institute and School of Medicine, University of California, Los Angeles School of Medicine, USA. McLachlanS@cshs.org
Rapoport
B
B
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000276:immunology; D007453:Iodide Peroxidase / Q000737:chemistry / Q000276:immunology*; D018448:Models, Immunological; D011487:Protein Conformation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D016207:Cytokines; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D007140:Immunoglobulin Fab Fragments; D007132:Immunoglobulin Isotypes; D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; D007453:Iodide Peroxidase