title: Non-MHC driven exacerbation of experimental thyroiditis in the postpartum period.
abstract: Many human autoimmune diseases, including those of the thyroid gland, are affected by immune changes during pregnancy and the postpartum period. To investigate this influence, we have developed an animal model of pregnancy thyroiditis by using thyroglobulin (Tg)-induced experimental autoimmune thyroiditis (EAT). We now report a study of the post-partum period in mice with EAT. At 5 weeks postpartum, which was 9 weeks after the completion of a Tg immunization regime, the mean thyroiditis grade was significantly increased in the postpartum group from 0.23 to 0.43 (p<0.05) and the thyroiditis Index, which reflected both the frequency and severity of thyroiditis, was similarly increased compared to controls (29.0 vs 9.0). When Tg immunized CBA/J (H-2k) female mice were mated with BALB/c (H-2d) males, there was a similar increase in the severity of thyroiditis in the postpartum period as seen with CBA/J males suggesting that allogeneic factors were not able to further this postpartum exacerbation. Spleen cell IL-4 secretion was enhanced in the postpartum but only in the presence of thyroiditis indicating enhanced activity of Th2 immune responses. There were no differences in IFN-gamma secretion, titers of anti-Tg, CD8+ & CD4+ T cells and T cell chemokine receptor (CCR5, CCR3) expression between non-pregnant control mice with thyroiditis and postpartum thyroiditis. In summary, we found that the severity of EAT during the postpartum was significantly greater than in non-pregnant control mice and was associated with enhanced Th2 immune responses. The allogenicity of the pregnancy had no influence on these findings. The lack of allogenic impact was in contrast to earlier observations in pregnancy itself where an exacerbation of thyroiditis was male strain-dependent and involved primarily Th1 responses. This indicated that the postpartum exacerbation of autoimmune thyroid disease was not a simple response to fetal antigens but secondary to unique postpartum factors.
authors.affiliation: Division of Endocrinology and Metabolism, Mount Sinai School of Medicine, New York, NY 10128, USA.
authors.forename: M
authors.initials: M
authors.lastname: Imaizumi
authors.forename: A
authors.initials: A
authors.lastname: Pritsker
authors.forename: M
authors.initials: M
authors.lastname: Kita
authors.forename: L
authors.initials: L
authors.lastname: Ahmad
authors.forename: P
authors.initials: P
authors.lastname: Unger
authors.forename: T F
authors.initials: TF
authors.lastname: Davies
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D049590:Postpartum Period / Q000276:immunology*; D011247:Pregnancy; D013154:Spleen / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000276:immunology* / Q000473:pathology
chemical_list: D007074:Immunoglobulin G; D015847:Interleukin-4; D007371:Interferon-gamma