This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kung, A. W. C. Articles by Jones, B. M. Search for Related Content PubMed PubMed Citation Articles by Kung, A. W. C. Articles by Jones, B. M.

A Change from Stimulatory to Blocking Antibody Activity in Graves’ Disease during Pregnancy¹

Departments of Medicine (A.W.C.K.) and Pathology (B.M.J.), University of Hong Kong, Queen Mary Hospital, Hong Kong, Republic of China

Address all correspondence and requests for reprints to: Dr. Annie W. C. Kung, Department of Medicine, University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, Republic of China.

Remission of Graves’ disease (GD) during pregnancy with recrudescence after delivery is commonly observed. However, as pregnancy is associated with type 2 rather than type 1 cytokine production, a decrease in thyroid-stimulating antibody (TSAb) activity alone is unlikely to account for the remission during pregnancy. We hypothesized that a change in the antibody characteristics may occur as pregnancy advances. Fifteen women were studied in the first, second, and third trimesters of pregnancy and 4 months postpartum. TSH receptor antibodies were determined using human thyroid cell cultures, and lymphocyte subsets were measured by flow cytometry.

Median TSAb (determined by cAMP release) decreased from 280% (96–3200) to 130% (range, 35–350; P < 0.05) during pregnancy, but no significant change was noted with the TSH binding inhibitory antibody (TBII; determined by RRA). Thyroid stimulation-blocking antibody (TSBAb; inhibition of TSH-stimulated cAMP release) increased from 16 ± 9% to 43 ± 16% (mean ± SD; P < 0.005). The increase in TSBAb was observed even among those patients who were in clinical remission before pregnancy. Overall, a negative correlation was observed between TSBAb activities and free T₄ levels during pregnancy (r = -0.279; P < 0.05). Reciprocal changes in TSAb, TBII, and TSBAb levels were observed in the seven patients who relapsed during the postpartum period. In comparison, the healthy pregnant women (n = 14) were all negative for TSAb, TBII, and TSBAb throughout pregnancy.

The absolute number of T lymphocytes, T helper cells, and natural killer cells, but not B cells, decreased significantly during pregnancy in both healthy women and GD patients. GD patients had significantly more CD5⁺ B cells at all stages of pregnancy compared to controls. In conclusion, a change in specificity from stimulatory to blocking antibodies was observed in GD patients during pregnancy and may contribute to the remission of GD during pregnancy.

This article has been cited by other articles:

				M. Rotondi, B. Pirali, S. Lodigiani, S. Bray, P. Leporati, S. Chytiris, S. Balzano, F. Magri, and L. Chiovato The post partum period and the onset of Graves' disease: an overestimated risk factor Eur. J. Endocrinol., August 1, 2008; 159(2): 161 - 165. [Abstract] [Full Text] [PDF]

				B. M. Casey and K. J. Leveno Thyroid disease in pregnancy. Obstet. Gynecol., November 1, 2006; 108(5): 1283 - 1292. [Abstract] [Full Text] [PDF]

				T. Muehlberg, J. A. Gilbert, P. V. Rao, A. M. McGregor, and J. P. Banga Dynamics of Thyroid-Stimulating and -Blocking Antibodies to the Thyrotropin Receptor in a Murine Model of Graves' Disease Endocrinology, April 1, 2004; 145(4): 1539 - 1545. [Abstract] [Full Text] [PDF]

				P. Rodien, N. Jordan, A. Lefevre, J. Royer, C. Vasseur, F. Savagner, A. Bourdelot, and V. Rohmer Abnormal stimulation of the thyrotrophin receptor during gestation Hum. Reprod. Update, March 1, 2004; 10(2): 95 - 105. [Abstract] [Full Text] [PDF]

				N. Amino, Y. Izumi, Y. Hidaka, K. Takeoka, Y. Nakata, K.-I. Tatsumi, A. Nagata, and T. Takano No Increase of Blocking Type Anti-Thyrotropin Receptor Antibodies During Pregnancy in Patients with Graves' Disease J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5871 - 5874. [Abstract] [Full Text] [PDF]

				T. Ando and T. F. Davies Postpartum Autoimmune Thyroid Disease: The Potential Role of Fetal Microchimerism J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 2965 - 2971. [Abstract] [Full Text] [PDF]

				P. V. Rao, P. F. Watson, A. P. Weetman, G. Carayanniotis, and J. P. Banga Contrasting Activities of Thyrotropin Receptor Antibodies in Experimental Models of Graves' Disease Induced by Injection of Transfected Fibroblasts or Deoxyribonucleic Acid Vaccination Endocrinology, January 1, 2003; 144(1): 260 - 266. [Abstract] [Full Text] [PDF]

				A. W. C. Kung, K. S. Lau, and L. D. Kohn Epitope Mapping of TSH Receptor-Blocking Antibodies in Graves' Disease That Appear during Pregnancy J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3647 - 3653. [Abstract] [Full Text] [PDF]

				A. P. Weetman Graves' Disease N. Engl. J. Med., October 26, 2000; 343(17): 1236 - 1248. [Full Text] [PDF]

				B. Buckingham The Hyperthyroid Fetus and Infant NeoReviews, June 1, 2000; 1(6): e103 - 109. [Full Text]