Journal of Clinical Endocrinology & Metabolism, Vol 74, 645-653, Copyright © 1992 by Endocrine Society

ARTICLES

A prospective study of lymphocyte-initiated immunosuppression in normal pregnancy: evidence of a T-cell etiology for postpartum thyroid dysfunction

A Stagnaro-Green, SH Roman, RH Cobin, E el-Harazy, S Wallenstein and TF Davies
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.

Immune function in normal pregnancy and the postpartum period remains poorly defined. We hypothesized that a comparative study between pregnant women with normal and abnormal immune function would further our understanding of the immune mechanisms of pregnancy. We chose to study a cohort of pregnant women at risk for the development of postpartum thyroid dysfunction (PPTD) as well as a group of normal controls. We chose PPTD as the model for abnormal immune function because of the relative ease of monitoring disease development and the relatively high prevalence for PPTD reported in earlier studies. Five hundred and fifty-two women were screened for the presence of thyroid autoantibodies in the first trimester of pregnancy. Thirty-three thyroid autoantibody-positive women and 28 thyroid autoantibody- negative women were followed prospectively throughout pregnancy and 6 months into the postpartum period. Lymphocyte subset analyses, thyroid function tests, and thyroid autoantibodies (antihuman thyroglobulin and antithyroid peroxidase) were performed at defined intervals. All patients were HLA serotyped. Normal pregnancy was principally characterized by decreased CD4+ T-cells and increasing CD8+ T-cells, causing a significant fall in the CD4+/CD8+ ratio in late pregnancy and into the postpartum period. Women who developed PPTD had 1) a higher CD4+/CD8+ ratio (P = 0.04), 2) activation of T-cells in the postpartum period (P = 0.02), and 3) significantly higher thyroid autoantibody titers (antihuman thyroglobulin, P = 0.02; antithyroid peroxidase, P = 0.0018). We found an overall incidence for PPTD of 8.8%. These data demonstrated that women who were thyroid autoantibody positive in the first trimester of pregnancy had a one in three chance of developing PPTD. We observed a significant fall in the T-cell helper/suppressor ratio in normal pregnant women, which was associated with distinct T- cell subset changes. This pregnancy-initiated T-cell regulation reflected an overall suppression of immune function. The development of PPTD was a frequent postpartum event in our population and was associated with a triad of immune markers: a reduction in the normal immune suppression of pregnancy (as indicated by higher T-cell helper/suppressor ratios), enhanced postpartum T-cell activation, and elevated thyroid autoantibodies. The reduction in the degree of immune suppression was, therefore, a major factor in the development of PPTD. Our results define immunological changes that occur in normal pregnancy and distinct immunological abnormalities necessary for the development of PPTD.

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