Soluble CD4 concentrations predict relapse of post-partum thyroiditis

Post-partum thyroiditis (PPT) is a common autoimmune thyroid disorder which results in significant morbidity at a critical time of a woman's life. The presence of anti-thyroglobulin (anti-TG) and, more so, anti-thryroperoxidase (anti-TPO) antibodies in the first trimester of pregnancy has been reported to forecast subsequent PPT. Despite their predictive value, these tests lack in specificity. We have sought to find an alternative that is more specific and, ideally, which could be tested immediately proximate to the event. We have taken advantage of the high recurrence rate of PPT in subsequent pregnancies to perform a prospective study of serum soluble CD4 (sCD4) and CD8 (sCD8) levels in 22 pregnant women who had at least one previous episode of PPT. This group was matched with 21 pregnant women of comparable age with no evidence of thyroid disease. Both groups of women were sampled in each of the three trimesters of pregnancy, 1 month, 3 months and 6 months post-partum for sCD4, sCD8, thyroid function parameters and antibodies. Twelve of the 22 women with previous PPT had recurrent disease; they were more likely to be cigarette smokers and to have a family history of autoimmune disorders (p<0.05, for both) than those who did not. Half of these women had high anti-TG or anti-TPO each in the first trimester compared to none among those without recurrent PPT and 2/21 controls. Serum sCD8 levels showed no changes over the observation points among the two PPT patient subsets and were comparable to those of the controls. By contrast, serum sCD4 concentrations showed divergent changes in the group with recurrent PPT in the course of pregnancy and postpartum period compared to those without disease recurrence and controls: sCD4 failed to show the physiological fall in the third trimester of pregnancy [19.0+/-1.7 (+/-SD) U/ml vs 15.6+/-2.3 U/ml in controls, NS]. This trend was continued into the first month post-partum when sCD4 levels were clearly higher than in controls (22.1+/-2.6 U/ml compared to 17.9+/-1.9 U/ml in controls, p<0.001) and well before the episode of PPT. An sCD4 serum level outside the 95% reference range at 1 month post-partum (9/12 in recurrent PPT, 1/21 in controls) yields a relative risk of 6.9 (chi2=14.67, p<0.001) compared to 3.3 for first trimester thyroid antibody positivity (p=0.029). In summary, we describe a reliable test for forecasting PPT that can be obtained immediately proximate to the possible event. If our findings are verified in larger studies, the measurement of serum sCD4 concentration drawn in the first month post-partum may prove an ideal test for population screening for impending PPT.