PMID- 8964863
OWN - NLM
STAT- MEDLINE
DCOM- 19961211
LR  - 20071114
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 81
IP  - 6
DP  - 1996 Jun
TI  - The interaction of a type A retroviral particle and class II human leukocyte 
      antigen susceptibility genes in the pathogenesis of Graves' disease.
PG  - 2271-9
AB  - We have previously reported that over 85% of patients with Graves' disease have 
      detectable serum antibodies against a human intracisternal type A retroviral 
      particle (HIAP), which are not present in age- and gender-matched controls, 
      suggesting a role for HIAP in triggering the autoimmune process leading to 
      Graves' disease. To investigate the interaction of this viral particle with 
      genetic factors, 35 members of 3 kindreds, selected because of a high family 
      prevalence of Graves' disease (a total of 11 members affected), were examined for 
      clinical signs of thyroid dysfunction, goiter, and opthalmopathy. Thyroid 
      function tests and autoimmune serological profiles were also obtained. In 
      addition, subjects were tested for the presence of antibodies against HIAP by 
      means of immunoblot analysis of their sera, and their human leukocyte antigen 
      (HLA) class II alleles were determined by DNA methodology. Molecular genetic 
      analyses enabled the detection of postulated HLA susceptibility haplotypes in 
      each family. These families had 8, 4, and 5 members, respectively, with such 
      apparent susceptibility genes and 11, 5, and 9 members, respectively, with 
      immunological evidence of retroviral exposure. In the presence of both factors 
      (codetected in a total of 15 members of the 3 kindreds), the incidence of Graves' 
      disease was 100%, 67%, and 80%, respectively. One additional member of family B 
      and 3 in family C with both viral and genetic susceptibility factors were found 
      to have serological abnormalities and/or goiter and ocular signs consistent with 
      evolving or preclinical Graves' disease. In families A and C, tight linkage 
      between HLA haplotypes and Graves' disease was demonstrated in a manner 
      consistent with recessive inheritance. The association between the occurrence of 
      both anti-HIAP-I antibody positivity and HLA susceptibility and the presence of 
      Graves' disease was highly significant (P < 0.001). The pathogenesis of Graves' 
      disease in these families appears to be attributable to the interaction between 
      the immune response to an intracisternal type A retroviral particle and 
      immunogenetic susceptibility, leading to the autoimmune processes that underlie 
      Graves' disease, with subsequent development of the characteristic features of 
      the illness. Data from these families suggest that both of these factors are 
      necessary for final disease expression. These results imply that serological 
      evidence of retroviral exposure together with genetic HLA susceptibility are the 
      two major predisposing factors underlying the pathogenesis of Graves' disease. 
      Further studies will establish whether prospective identification of persons at 
      risk for Graves' disease is possible by this means.
FAU - Jaspan, J B
AU  - Jaspan JB
AD  - Department of Medicine, Tulane University School of Medicine, New Orleans, 
      Louisiana 70112, USA.
FAU - Sullivan, K
AU  - Sullivan K
FAU - Garry, R F
AU  - Garry RF
FAU - Lopez, M
AU  - Lopez M
FAU - Wolfe, M
AU  - Wolfe M
FAU - Clejan, S
AU  - Clejan S
FAU - Yan, C
AU  - Yan C
FAU - Tenenbaum, S
AU  - Tenenbaum S
FAU - Sander, D M
AU  - Sander DM
FAU - Ahmed, B
AU  - Ahmed B
FAU - Bryer-Ash, M
AU  - Bryer-Ash M
LA  - eng
GR  - 5M01-RR-05096-05/RR/NCRR NIH HHS/United States
GR  - DE-10862/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Antibodies, Viral)
RN  - 0 (Autoantibodies)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Adult
MH  - Antibodies, Viral/analysis
MH  - Autoantibodies/analysis
MH  - Female
MH  - *Genes
MH  - Genetic Predisposition to Disease
MH  - Graves Disease/*genetics/immunology/physiopathology
MH  - Haplotypes
MH  - Histocompatibility Antigens Class II/*genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Retroviridae/immunology/*physiology
MH  - Thyroid Gland/physiopathology
MH  - Virion/*physiology
EDAT- 1996/06/01 00:00
MHDA- 1996/06/01 00:01
CRDT- 1996/06/01 00:00
PHST- 1996/06/01 00:00 [pubmed]
PHST- 1996/06/01 00:01 [medline]
PHST- 1996/06/01 00:00 [entrez]
AID - 10.1210/jcem.81.6.8964863 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1996 Jun;81(6):2271-9. doi: 10.1210/jcem.81.6.8964863.