title: Antibodies to thyroid peroxidase arise spontaneously with age in NOD.H-2h4 mice and appear after thyroglobulin antibodies.
abstract: Hashimoto's thyroiditis, a common autoimmune disease, is associated with autoantibodies to thyroglobulin (Tg) and thyroid peroxidase (TPO). TPO, unlike abundant and easily purified Tg, is rarely investigated as an autoantigen in animals. We asked whether antibodies (Abs) develop to both TPO and Tg in thyroiditis that is induced (C57BL/6 and DBA/1 mice) or arises spontaneously (NOD.H-2h4 mice). Screening for TPOAbs was performed by flow cytometry using mouse TPO-expressing eukaryotic cells. Sera were also tested for binding to purified mouse Tg and human TPO. The antibody data were compared with the extent of thyroiditis. Immunization with mouse TPO adenovirus broke self-tolerance to this protein in C57BL/6 mice, but thyroiditis was minimal and TgAbs were absent. In DBA/1 mice with extensive granulomatous thyroiditis induced by Tg immunization, TPOAbs were virtually absent despite high levels of TgAbs. In contrast, antibodies to mouse TPO, with minimal cross-reactivity with human TPO, arose spontaneously in older (7-12 months) NOD.H-2h4 mice. Unexpectedly, TgAbs preceded TPOAbs, a time course paralleled in relatives of probands with juvenile Hashimoto's thyroiditis. These findings demonstrate a novel aspect of murine and human thyroid autoimmunity, namely breaking B cell self-tolerance occurs first for Tg and subsequently for TPO.
authors.affiliation: Thyroid Autoimmune Disease Unit, Cedars-Sinai Research Institute and University of California, Los Angeles School of Medicine, Los Angeles, California 90048, USA.
authors.forename: Chun-Rong
authors.initials: CR
authors.lastname: Chen
authors.forename: Sepehr
authors.initials: S
authors.lastname: Hamidi
authors.forename: Helen
authors.initials: H
authors.lastname: Braley-Mullen
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nagayama
authors.forename: Catherine
authors.initials: C
authors.lastname: Bresee
authors.forename: Holly A
authors.initials: HA
authors.lastname: Aliesky
authors.forename: Basil
authors.initials: B
authors.lastname: Rapoport
authors.forename: Sandra M
authors.initials: SM
authors.lastname: McLachlan
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D016466:CHO Cells; D019556:COS Cells; D002648:Child; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007114:Immunization / Q000379:methods; D007453:Iodide Peroxidase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016688:Mice, Inbred NOD; D008875:Middle Aged; D013954:Thyroglobulin / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000276:immunology / Q000473:pathology; D013997:Time Factors; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D013954:Thyroglobulin; D007453:Iodide Peroxidase