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Human Reproduction, Vol. 15, No. 5, 1163-1169, May 2000
© 2000 European Society of Human Reproduction and Embryology

Peripheral natural killer cytotoxicity and CD56posCD16pos cells increase during early pregnancy in women with a history of recurrent spontaneous abortion

Peter M. Emmer1,4, Willianne L.D.M. Nelen2, Eric A.P. Steegers2, Jan C.M. Hendriks3, Margret Veerhoek1 and Irma Joosten1

1 Blood Transfusion Service, 2 Department of Gynaecology and Obstetrics and 3 Department of Medical Statistics, University Hospital Nijmegen, PO Box 9101, 6500 HB, The Netherlands

For diagnostic purposes we assessed peripheral natural killer (NK) cell cytotoxicity and NK and T cell numbers to assess their putative predictive value in recurrent spontaneous abortion (RSA). A total of 43 women with subsequent pregnancy, 37 healthy controls and 39 women successfully partaking in an in-vitro fertilization (IVF) procedure, were included in the study. We show that before pregnancy, levels of NK cytotoxicity and numbers of both single CD56pos and double CD56posCD16pos cells were similar between RSA women and controls. But notably, within the RSA group, NK cell numbers of <12% were strongly associated with a subsequent pregnancy carried to term. Supplementation of folic acid led to an increase of single CD56pos cells, but cytotoxic function appeared unaffected. The expression pattern of killer inhibitory receptors on CD56pos cells was not different between patients and controls. A longitudinal study revealed that, compared with controls, in RSA women higher numbers of double CD56posCD16pos cells were present during early pregnancy, paralleled by an increase in cytotoxic NK cell reactivity. The single CD56pos population decreased in number. In conclusion, the analysis of peripheral NK cell characteristics appears a suitable diagnostic tool in RSA. Immunomodulation aimed at NK cell function appears a promising therapeutic measure.

Key words: abortion/CD56/folic acid/KIR/natural killer cells

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