PMID- 12039412
OWN - NLM
STAT- MEDLINE
DCOM- 20021114
LR  - 20190906
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 63
IP  - 4
DP  - 2002 Apr
TI  - HLA-DR and HLA-DQ polymorphism in human thyroglobulin-induced autoimmune 
      thyroiditis: DR3 and DQ8 transgenic mice are susceptible.
PG  - 301-10
AB  - 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.
FAU - Wan, Qiang
AU  - Wan Q
AD  - Department of Immunology and Microbiology, Wayne State University School of 
      Medicine, Detroit, MI 48201, USA.
FAU - Shah, Rajal
AU  - Shah R
FAU - Panos, John C
AU  - Panos JC
FAU - Giraldo, Alvaro A
AU  - Giraldo AA
FAU - David, Chella S
AU  - David CS
FAU - Kong, Yi chi M
AU  - Kong Yc
LA  - eng
GR  - AI14764/AI/NIAID NIH HHS/United States
GR  - DK45960/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ6 antigen)
RN  - 0 (HLA-DQ8 antigen)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DR3 Antigen)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*03:01 antigen)
RN  - 9010-34-8 (Thyroglobulin)
SB  - IM
MH  - Animals
MH  - Disease Susceptibility
MH  - HLA-DQ Antigens/genetics/*immunology
MH  - HLA-DR Antigens/genetics
MH  - HLA-DR3 Antigen/genetics/*immunology
MH  - HLA-DRB1 Chains
MH  - Humans
MH  - Immunity, Innate
MH  - Mice
MH  - Mice, Transgenic
MH  - Polymorphism, Genetic
MH  - Thyroglobulin/*adverse effects
MH  - Thyroiditis, Autoimmune/chemically induced/*immunology
EDAT- 2002/06/01 10:00
MHDA- 2002/11/26 04:00
CRDT- 2002/06/01 10:00
PHST- 2002/06/01 10:00 [pubmed]
PHST- 2002/11/26 04:00 [medline]
PHST- 2002/06/01 10:00 [entrez]
AID - S0198885902003609 [pii]
AID - 10.1016/s0198-8859(02)00360-9 [doi]
PST - ppublish
SO  - Hum Immunol. 2002 Apr;63(4):301-10. doi: 10.1016/s0198-8859(02)00360-9.