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Evidence that MHC I-E dampens thyroid autoantibodies and prevents spreading to a second thyroid autoantigen in I-Ak NOD mice

Genes & Immunity volume 16, pages 268–274 (2015)Cite this article

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Abstract

NOD.H2k and NOD.H2h4 mice carry the major histocompatibility complex (MHC) class II molecule I-Ak associated with susceptibility to experimentally induced thyroiditis. Dietary iodine-enhanced spontaneous thyroid autoimmunity, well known in NOD.H2h4 mice, has not been investigated in NOD.H2k mice. We compared NOD.H2h4 and NOD.H2k 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.H2h4 compared with NOD.H2k mice on NaI, and TPOAb developed in NOD.H2h4 mice but not in NOD.H2k mice. DNA exome analysis revealed, in addition to the differences in the chromosome (Chr) 17 MHC regions, that NOD.H2k mice, and particularly NOD.H2h4 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.H2h4 and NOD.H2k 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.H2h4 and NOD.H2k mice in TgAb levels and, as in humans, autoantibody spreading to TPO.

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Acknowledgements

We thank Dr Yaron Tomer (Division of Endocrinology, Department of Medicine, Mount Sinai School of Medicine) for determining the exon 10 Tg haplotypes in DNA from NOD.H2h4, NOD and B10.A4 R mice. We also thank Fanny DeWilde for her help in the animal housing facility in Montreal and Catherine Bresee (Cedars-Sinai Medical Center) for statistical advice. We are grateful to Dr Jean Ruf (INSERM-URA, Faculté de Médecine, Marseille, France) for generously providing us with mouse monoclonal antibodies to human TPO. This work was supported by the following grants: NIH DK 54684, NIH DK 082390 (to SMM) and Canadian Diabetes Association OG-3-13-4018 (to SL).

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Author notes

  1. S Lesage and S M McLachlan: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montréal, QC, Canada

    A-N Pelletier, G Chabot-Roy & S Lesage

  2. Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada

    A-N Pelletier & S Lesage

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

    H A Aliesky, B Banuelos, B Rapoport & S M McLachlan

Authors
  1. A-N Pelletier
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  2. H A Aliesky
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  3. B Banuelos
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  4. G Chabot-Roy
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  6. S Lesage
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  7. S M McLachlan
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Correspondence to S M McLachlan.

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Pelletier, AN., Aliesky, H., Banuelos, B. et al. Evidence that MHC I-E dampens thyroid autoantibodies and prevents spreading to a second thyroid autoantigen in I-Ak NOD mice. Genes Immun 16, 268–274 (2015). https://doi.org/10.1038/gene.2015.7

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