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

Abstract

Objectives: 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.

Materials and methods: 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.

Results: 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).

Conclusion: 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.