Microchimerism and blocking activity in women with recurrent spontaneous abortion (RSA) after alloimmunization with the partner's lymphocytes

Alloimmunization therapy using the partner's leukocytes has been reported t o be effective in preventing the failure of pregnancy in patients who have suffered RSA of unknown cause. After alloimmunization, several investigator s have reported the presence of blocking factors (BF) in women with success ful pregnancies in in vitro assays of lymphocyte response. The recent disco very of small numbers of ubiquitous donor cells (microchimerism) in human t ransplants up to 29 years post-transplantation has raised questions about t he migration of the chimeric cells and their role in the induction and perp etuation of tolerance. We have investigated the production of BF in the mix ed lymphocyte reaction (MLR) before and in some patients after alloimmuniza tion and its possible relation with the development of microchimerism (M). Before the treatment we studied 14 couples with three or more abortions who were evaluated clinically to rule-out genetic, structural, endocrine, infe ctious and autoimmune causes. The M study was done by nested PCR-SSP techni que with HLA-DR alleles, before and after 30 days of the last immunization. Before the treatment only one patient was M positive and none were BF posi tive with inhibition effect (IE) > 50. Only eight underwent treatment. The patients had between three and nine alloimmunizations ((x) over bar = 4.7). After treatment, all patients were M positive with IE > 50. Six months aft er the last immunization, four patients are M positive with IE > 50. In con clusion, the hypothesis proposes that alloimmunization establishes a state of microchimerism that would be the necessary allogeneic stimulus for T-cel l activation, and the induction or maintenance of tolerance to the fetus du ring pregnancy. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.