title: Evidence that MHC I-E dampens thyroid autoantibodies and prevents spreading to a second thyroid autoantigen in I-A(k) NOD mice.
abstract: NOD.H2(k) and NOD.H2(h4) mice carry the major histocompatibility complex (MHC) class II molecule I-A(k) associated with susceptibility to experimentally induced thyroiditis. Dietary iodine-enhanced spontaneous thyroid autoimmunity, well known in NOD.H2(h4) mice, has not been investigated in NOD.H2(k) mice. We compared NOD.H2(h4) and NOD.H2(k) strains for thyroiditis and autoantibodies to thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) without or with dietary sodium iodide (NaI) for up to 32 weeks. TgAb levels were significantly higher in NOD.H2(h4) compared with NOD.H2(k) mice on NaI, and TPOAb developed in NOD.H2(h4) mice but not in NOD.H2(k) mice. DNA exome analysis revealed, in addition to the differences in the chromosome (Chr) 17 MHC regions, that NOD.H2(k) mice, and particularly NOD.H2(h4) mice, have substantial non-MHC parental DNA. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis highlighted thyroid autoimmunity and immune-response genes on Chr 17 but not on Chr 7, and 15 parental B10.A4R DNA. Studies of parental strains provided no evidence for non-MHC gene contributions. The exon 10 Tg haplotype, associated with experimentally induced thyroiditis, is absent in NOD.H2(h4) and NOD.H2(k) mice and is not a marker for spontaneous murine thyroid autoimmunity. In conclusion, the absence of I-E is a likely explanation for the difference between NOD.H2(h4) and NOD.H2(k) mice in TgAb levels and, as in humans, autoantibody spreading to TPO.
authors: 1] Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montréal, QC, Canada [2] Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada.
authors: A-N
authors: AN
authors: Pelletier
authors: Thyroid Autoimmune Disease Unit, Cedars-Sinai Research Institute and UCLA School of Medicine, University of California, Los Angeles, CA, USA.
authors: H A
authors: HA
authors: Aliesky
authors: Thyroid Autoimmune Disease Unit, Cedars-Sinai Research Institute and UCLA School of Medicine, University of California, Los Angeles, CA, USA.
authors: B
authors: B
authors: Banuelos
authors: Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montréal, QC, Canada.
authors: G
authors: G
authors: Chabot-Roy
authors: Thyroid Autoimmune Disease Unit, Cedars-Sinai Research Institute and UCLA School of Medicine, University of California, Los Angeles, CA, USA.
authors: B
authors: B
authors: Rapoport
authors: 1] Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montréal, QC, Canada [2] Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada.
authors: S
authors: S
authors: Lesage
authors: Thyroid Autoimmune Disease Unit, Cedars-Sinai Research Institute and UCLA School of Medicine, University of California, Los Angeles, CA, USA.
authors: S M
authors: SM
authors: McLachlan
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology* / Q000378:metabolism; D015551:Autoimmunity / Q000276:immunology; D059472:Exome; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007453:Iodide Peroxidase / Q000276:immunology; D008297:Male; D016688:Mice, Inbred NOD / Q000235:genetics / Q000276:immunology; D012974:Sodium Iodide / Q000009:adverse effects; D013954:Thyroglobulin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013961:Thyroid Gland / Q000276:immunology*; D013966:Thyroiditis / Q000235:genetics / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000139:chemically induced / Q000235:genetics / Q000276:immunology
chemical_list: D001323:Autoantibodies; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D013954:Thyroglobulin; D007453:Iodide Peroxidase; D012974:Sodium Iodide