HLA-DR and HLA-DQ polymorphism in human thyroglobulin-induced autoimmune thyroiditis: DR3 and DQ8 transgenic mice are susceptible.

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  • Author(s): Wan Q;Wan Q; Shah R; Panos JC; Giraldo AA; David CS; Kong Yc
  • Source:
    Human immunology [Hum Immunol] 2002 Apr; Vol. 63 (4), pp. 301-10.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier/North-Holland Country of Publication: United States NLM ID: 8010936 Publication Model: Print Cited Medium: Print ISSN: 0198-8859 (Print) Linking ISSN: 01988859 NLM ISO Abbreviation: Hum Immunol Subsets: MEDLINE
    • Publication Information:
      Original Publication: [New York] Elsevier/North-Holland.
    • Subject Terms:
      HLA-DQ Antigens/*immunology ; HLA-DR3 Antigen/*immunology ; Thyroglobulin/*adverse effects ; Thyroiditis, Autoimmune/*immunology; Animals ; Disease Susceptibility ; HLA-DQ Antigens/genetics ; HLA-DR Antigens/genetics ; HLA-DR3 Antigen/genetics ; HLA-DRB1 Chains ; Humans ; Immunity, Innate ; Mice ; Mice, Transgenic ; Polymorphism, Genetic ; Thyroiditis, Autoimmune/chemically induced
    • Abstract:
      In contrast to H2-based susceptibility to experimental autoimmune thyroiditis (EAT) induced with thyroglobulin (Tg), human leukocyte antigen (HLA) association with Hashimoto's thyroiditis, the human counterpart, is less clear, and determining association is further complicated by DR/DQ linkage disequilibrium. Previously, we addressed the controversial implication of HLA-DR genes by introducing HLA-DRA/DRB1*0301 (DR3) transgene into endogenous class II negative H2Ab(0) mice. EAT induction with either human (h) or mouse (m) Tg demonstrated the permissiveness of DR3 molecules for shared Tg epitopes. Here, we examined the participation of HLA-DQ genes by introducing DQA1*0301/DQB1*0302 (DQ8) transgene into class II negative Ab(0) or class I and II negative beta(2)m((-/-)) Ab(0) mice. About 50% and 80% of HLA-DQ8(+) Ab(0) and beta(2)m(-) Ab(0) mice, respectively, developed moderate EAT after hTg immunization, but only minimal response to mTg. The hTg presentation to hTg-primed cells was blocked by anti-DQ mAb in vitro. By contrast, HLA-DRB1*1502 (DR2) and *0401 (DR4) transgenes contributed little to hTg induction. Similarly, DQA1*0103/DQB1*0601 or DQA1*0103/DQB1*0602 (DQ6) transgenic Ab(0) mice were unresponsive to hTg induction and carried no detectable influence in DQ8/DQ6 double transgenic mice. Thus, both HLA-DR and -DQ polymorphism exists for hTg in autoimmune thyroiditis. The use of defined single or double transgenic mice obviates the complications seen in polygenic human studies.
    • Grant Information:
      AI14764 United States AI NIAID NIH HHS; DK45960 United States DK NIDDK NIH HHS
    • Accession Number:
      0 (HLA-DQ Antigens)
      0 (HLA-DQ6 antigen)
      0 (HLA-DQ8 antigen)
      0 (HLA-DR Antigens)
      0 (HLA-DR3 Antigen)
      0 (HLA-DRB1 Chains)
      0 (HLA-DRB1*03:01 antigen)
      9010-34-8 (Thyroglobulin)
    • Publication Date:
      Date Created: 20020601 Date Completed: 20021114 Latest Revision: 20190906
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/s0198-8859(02)00360-9
    • Accession Number:
      12039412