A change from stimulatory to blocking antibody activity in Graves' disease during pregnancy

J Clin Endocrinol Metab. 1998 Feb;83(2):514-8. doi: 10.1210/jcem.83.2.4598.

Abstract

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.

MeSH terms

  • Antibodies, Blocking / blood*
  • Autoantibodies / blood*
  • Cells, Cultured
  • Female
  • Graves Disease / blood
  • Graves Disease / immunology*
  • Humans
  • Immunoglobulins, Thyroid-Stimulating / blood*
  • Immunoglobulins, Thyroid-Stimulating / immunology
  • Killer Cells, Natural
  • Lymphocyte Count
  • Pregnancy
  • Pregnancy Complications / immunology*
  • Prospective Studies
  • Receptors, Thyrotropin / blood*
  • Remission, Spontaneous
  • T-Lymphocytes
  • T-Lymphocytes, Helper-Inducer
  • Thyroxine / blood

Substances

  • Antibodies, Blocking
  • Autoantibodies
  • Immunoglobulins, Thyroid-Stimulating
  • Receptors, Thyrotropin
  • thyrotropin-binding inhibitory immunoglobulin
  • Thyroxine