A CHANGE FROM STIMULATORY TO BLOCKING ANTIBODY-ACTIVITY IN GRAVES-DISEASE DURING PREGNANCY

Remission of Graves' disease (GD) during pregnancy with recrudescence after delivery is commonly observed. However, as pregnancy is associat ed with type 2 rather than type 1 cytokine production, a decrease in t hyroid-stimulating antibody (TSAb) activity alone is unlikely to accou nt for the remission during pregnancy. We hypothesized that a change i n the antibody characteristics may occur as pregnancy advances. Fiftee n women were studied in the first, second, and third trimesters of pre gnancy and 4 months postpartum. TSH receptor antibodies were determine d using human thyroid cell cultures, and lymphocyte subsets were measu red by flow cytometry. Median TSAb (determined by cAMP release) decrea sed from 280% (96-3200) to 130% (range, 35-350; P < 0.05) during pregn ancy, but no significant change was noted with the TSH binding inhibit ory antibody (TBII; determined by RRA. Thyroid stimulation-blocking an tibody (TSBAb; inhibition of TSH-stimulated cAMP release) increased fr om 16 +/- 9% to 43 + 16% (mean +/- SD; P < 0.005). The increase in TSB Ab was observed even among those patients who were in clinical remissi on before pregnancy. Overall, a negative correlation was observed betw een TSBAb activities and free T-4 levels during pregnancy (r = -0.279; P < 0.05). Reciprocal changes in TSAb, TBII, and TSBAb levels were ob served 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 G D during pregnancy.