CELL-MEDIATED-IMMUNITY AND POSTPARTUM THYROID-DYSFUNCTION - A POSSIBILITY FOR THE PREDICTION OF DISEASE

Postpartum (pp) thyroid dysfunction (PPTD) is thought to be caused by an autoimmune (AI) process [already present in pregnancy, as shown by the positivity for thyroid peroxidase antibodies (TPO-Ab)] becomes ove rt disease in the pp period, and one assumes that this exacerbation re presents a rebound phenomenon after a general immunosuppression during pregnancy. The presence of TPO-Ab in pregnancy has been suggested as a predictor for later PPTD development. Apart from B cells, eg product ion of autoantibodies, various functions of the cell-mediated immune ( CMI) system, including those of peripheral T cells, monocytes, and den dritic cells (DC), are also disturbed in AI states. The objectives of the present study were: determining alterations in various CMI paramet ers in pregnancies followed by PPTD vs. those not followed by PPTD; an d determining the usefulness of these parameters in the prediction of PPTD. In a prospective study (region: Kempenland, southeast Netherland s), a random sample of 291 women were tested at 12 and 32 weeks gestat ion and 4 weeks pp for TPO-Ab (n=26); and thyroidological uneventful c ontrol women of the same cohort, matched for age and parity (n=21), we re tested for thyroid-stimulating antibodies, percentages of periphera l blood lymphocyte subsets using fluorescence-activated cell sorter an alysis (CD3, CD4, CD8, CD16, CD56, major histocompatibility complex-cl ass II), for monocyte polarization, and for cluster capability of mono cyte-derived DC. Results were: 1) 31 women (10.7%) were positive for T PO-Ab (TPO-Ab(+)) in gestation (12 and/or 32 weeks); 2) 15 women (5.2% ) developed PPTD, of whom 10 were TPO-Ab(+) in gestation; 3) pregnancy -related CMI alterations consisted of low percentages of CD16(+)CD56() natural killer (NK) cells and a low DC cluster capability at 12 week s gestation (these functions were normalized at 32 weeks gestation); 4 ) the TPO-Ab(+) PPTD+ women (4 hyper, 5 hypo, and 1 hyper/hypo) were c haracterized by a persistently low percentage of NK cells, a lowered m onocyte polarization, and a raised percentage of major histocompatibil ity complex-class II(+)CD3(+) T cells; 5)the TPO-Ab(-)PPTD(+) women (a ll 5 hyper) had neither thyroid-stimulating antibodies nor CMI alterat ions, apart from those normally seen in pregnancy; 6) 21 women were po sitive for TPO-Ab in pregnancy but did not develop PPTD (they had the same lowered NK cell percentages and monocyte polarization as the TPO- Ab(+)PPTD(+) cases, but they had normal percentages of activated perip heral T cells and a lower titer of TPO-Ab); 7)determination of the num ber of NK cells and monocyte polarization hardly contributed to the pr ediction of PPTD (as compared with TPO-Ab status), because of strong i nterindividual variation and close association with the presence of TP O-Ab; and 8) combining TPO-Ab assays with testing for activated T cell s was the most optimal parameter for the prediction of TPO-Ab(+) cases of PPTD in our small test set. We conclude that TPO-Ab(+) pregnant wo men who develop PPTD show several CMI abnormalities other than those s een in normal pregnant women, such as persistently lower percentage of NK cells, a lowered monocyte polarization, and a raised percentage of activated T cells. The latter seems rather specific for the actual PP TD development and is not found in TPO-Ab(+) (but PPTD) uncomplicated pregnancies. TPO-Ab(-) (but PPTD+) women had no signs of CMI abnormali ties (apart from those specific for the pregnancy state). Although stu died cases are low in number, our data are suggestive for the existenc e of two forms of PPTD: a TPO-Ab(+) (AI) form (two-thirds of patients, classical PPTD pattern); and a TPO-Ab(-) (non-AI) form (one-third of patients, only hyper). Such assumption implies that, at best, two-thir ds of PPTD cases can be predicted using either humoral and/or cellular immune tests.