Soluble HLA-DR and soluble CD95 ligand levels in pregnant women with antiphospholipid syndromes V. Rebmann E. Ronin-Walknowska O. Sipak-Szmigiel A. Miklaszewicz E. Czajkowska H. Grosse-Wilde Authors’ affiliations: V. Rebmann 1 , E. Ronin-Walknowska 2 , O. Sipak-Szmigiel 2 , A. Miklaszewicz 3 , E. Czajkowska 2 , H. Grosse-Wilde 1 1 Institute of Immunology, University Hospital of Essen, Essen, Germany, 2 Department for Pathology of Pregnancy and Labor, Pomeranian Medical University, Szczecin, Poland, 3 Department of Microbiology and Immunology, Pomeranian Medical University, Szczecin, Poland Correspondence to: Prof Dr Hans Grosse-Wilde Institut fu ¨r Immunologie Universita ¨tsklinikum Essen Virchowstreet 171 D-45122 Essen, Germany Tel: þ49-201-723-4200 Fax: þ49-201-723-5906 e-mail: immunologie@uni- essen.de Abstract: Antiphospholipid syndrome (APS) is a severe complication in pregnancy that can lead to fetal death in the second or third trimester. As soluble HLA-DR (sHLA-DR) molecules are reported to be implicated in the etiology of pregnancy disorders and of autoimmune diseases, we studied sHLA-DR plasma levels in pregnant women with APS (n ¼ 14) and in women with normal pregnancy (n ¼ 15), in women with high-risk pregnancies such as preeclampsia (PE; n ¼ 20) and intrauterine growth retardation (IUGR; n ¼ 10) and in fertile non-pregnant women (n ¼ 29). The sHLA-DR levels of pregnant women were assessed during the third trimester, at labor, in the first week, and in the third month of puerperium. The results obtained were compared with soluble CD95 ligand (sCD95L), an important signal molecule in the apoptosis pathway. The sHLA-DR levels in pregnant women with APS were approximately three times higher (mean 1.48  0.15 mg/ml) during the whole observation period than in fertile non-pregnant women (0.54  .06 mg/ ml) and nearly double in women with high risk (PE, 0.91  14 mg/ml; IUGR, 0.94  .21 mg/ml) and in normal pregnancies (0.74  0.13 mg/ml). Furthermore, sHLA-DR levels of pregnant women with APS were positively correlated with the serum concentration of anti-anticardiolipin immunoglobulin G antibodies. For sCD95L plasma levels, no substantial variations were found among the different groups above. In pregnant women with APS, however, sHLA-DR levels were positively correlated with sCD95L levels. Further studies should clarify the functional involvement of sHLA-DR molecules in the induction of CD95/CD95L-mediated apoptosis pathway that may play a crucial role in the pathology of pregnancies complicated by APS. As the fetus represents an allograft for the maternal immune system, the induction and maintenance of maternal immune tolerance is of central importance for the implantation of the conceptus into the maternal uterus as well as for its survival and growth. Although to date the exact mechanisms for the down-regulation of the maternal immune response against the paternal antigens of the fetus are not well understood, there is a general consensus that local or peripheral mechanisms are involved to establish this fetus-specific tolerance (1, 2). Several unique features of the fetus promote local tolerance. Among them, the lack of classical histocompatibility antigen (HLA) Key words: antiphospholipid syndrome; intrauterine growth retardation; preeclampsia-soluble HLA-DR; soluble CD95 ligand Acknowledgments: This work was supported by a grant (No. 4 PO5E 011 10) by the State Committee for Scientific Research. The study protocol was approved by the Ethics Committee of the Pomeranian Medical University. Received 20 March 2003, revised 1 July 2003, accepted for publication 22 July 2003 Copyright ß Blackwell Munksgaard 2003 Tissue Antigens. Tissue Antigens 2003: 62: 536–541 Printed in Denmark. All rights reserved 536