Mixed lymphocyte reaction blocking factors (MLR-Bf) as potential biomarker for indication and efficacy of paternal lymphocyte immunization in recurrent spontaneous abortion

Abstract

The majority of cases of unexplained recurrent spontaneous abortion (RSA) remains unclear and is found to be associated with alloimmune antibodies termed as mixed lymphocyte reaction blocking factor (MLR-Bf). The decreased production of MLR-Bf may play major role in the immunologic failure of pregnancy and can lead to abortion. The present study was aimed at evaluating MLR-Bf as potential biomarker of indication and the efficacy of immunotherapy with paternal lymphocytes (LIT) in women with RSA. A total of 97 women with history of unexplained RSA were recruited for this prospective study. These women showed negative for MLR-Bf and registered for lymphocyte immunotherapy with husband cells. Women with autoimmune pathology or anti-phospholipid syndrome were excluded. All individuals gave their consent to participate in the study. We have analyzed MLR proliferative response and MLR-Bf in nonpregnant women with history of RSA before and after LIT. Following LIT, the initially low MLR proliferative response was restored at 76.6% of women, and MLR-Bf activity in blood serum could be detected in 74% of women. The rate of successful pregnancy was shown to be significantly higher in women positive for MLR-Bf (50/72) as compared with the MLR-Bf negative women (7/25; χ (2)=0.0003). The data obtained demonstrate that LIT with the paternal lymphocytes in MLR-Bf negative women is accompanied by increased proliferative cell response to the paternal alloantigens and by enhanced production of soluble suppressor activity factors (MLR-Bf) that is associated with improved pregnancy outcome in women with history of RSA.