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Human Reproduction, Vol. 18, No. 11, 2465-2472, November 2003
© 2003 European Society of Human Reproduction and Embryology

Prospective, serial investigations of in-vitro lymphocyte cytokine production, CD62L expression and proliferative response to microbial antigens in women with recurrent miscarriage

C. Kruse1,4, K. Varming2 and O.B. Christiansen3

1 Department of Obstetrics and Gynaecology and 2 Department of Clinical Immunology, Aalborg Hospital, Aalborg and 3 Fertility Clinic 4071, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

4 To whom correspondence should be addressed at: Rolighedsvej 6, DK-9400 Norresundby, Denmark. e-mail: ckruse{at}dadlnet.dk

BACKGROUND: Lymphocytes from pregnant women with unexplained recurrent miscarriage (RM) may be characterized by a T-helper type 1-dominated cytokine production and a higher proliferative response to microbial recall antigens compared with normal pregnant women. METHODS: Serial blood samples were taken from 14 women with RM (at least three previous consecutive miscarriages) during the first 14 weeks of pregnancy, and one blood sample was taken from 15 control women in gestational weeks 7–8. Of the 14 pregnant RM patients, four produced a live birth and 10 miscarried. Lymphocytes were in-vitro-stimulated by mitogens, allogeneic cells and microbial antigens, and the production of a series of cytokines, the proliferative responses and lymphocytic expression of CD62L (which may be a marker of T-helper type 2 lymphocytes) were measured. RESULTS: Repeated measurements of cytokine production were reproducible during the first trimester. The proliferative responses to herpes simplex and tetanus antigens were increased, and the ratio of CD62L–/CD62L+ expressing CD4+CD45RO+ lymphocytes was decreased in patients compared with controls (P = 0.01, P < 0.01 and P < 0.01 respectively). CONCLUSION: The results of the in-vitro assays used were reproducible in serial testing during pregnancy. The importance of CD62L expression on lymphocytes for RM and the relevance of the maternal response to microbial antigens during pregnancy should be further explored.

Key words: abortion/cytokines/L-selectin/recall antigens/recurrent miscarriage


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