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

Abstract

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.

Studies on the Infants Born to the Patients with Unexplained Recurrent Abortion Who Underwent Immunotherapy using their Husband’s Lymphocytes

“…In recent reports Liang et al pointed out that NK cytotoxicity and Th1/Th2 ratios were significantly decreased in the successful conception group after the immunotherapy [24]. Furthermore, Khonina et al suggested that the immunotherapy for patients negative for MLR-BAbs is accompanied by an increased proliferative cell response to the paternal alloantigens and enhanced production of soluble suppressor activity factors that is associated with improved pregnancy outcomes in women with URA [33].…”

“…The strength of blastoformation of the maternal lymphocytes was evaluated, and the MLR-blocking effect was calculated by the formula below. An MLR-blocking effect ≥22% was designated as positive for MLR-Babs [10,19,22,33].…”

“…Immunotherapy for these patients using their husbands' or a third party's leukocytes has been reported [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. Although the efficacy of this modality has been controversial, an analysis of controlled clinical trials revealed the efficacy for patients with Unexplained Recurrent Abortion (URA) [7,14,19,26,27], especially for those who were negative for blocking antibodies evaluated by a mixed lymphocyte culture reaction between spouses (MLR-BAbs) [19,22,[28][29][30][31][32][33]. The outcome of pregnancies, especially the condition of infants (such as the body weight of infants or the number of gestational weeks at which the infants were born) of patients after this immunotherapy, has not been fully elucidated, although some articles suggested absence of harmfulness of this immunotherapy for the infants born to immunized patients [34][35][36][37][38][39].…”

Paternal Lymphocyte Alloimmunization in the Treatment of Infertility: A New Look at an Old Problem

“…Большинство авторов подчеркивают высокую эффективность АИЛ в лечение ПНБ [9,13,15,16,19,23,29]. В то же время в ряде исследований не выявлено достоверного увеличения числа ро-дов на фоне АИЛ [30,37].…”

“…Проведенные нами ранее исследования, на-правленные на поиск биомаркеров, ассоцииро-ванных с бесплодием неясного генеза, проде-монстрировали, что среди ряда параметров (ответ в СКЛ, активность БФ, оценка активированных НК клеток, Treg и цитокинового баланса), дефи-цит БФ являлся наиболее частым нарушением, выявляемым у преобладающего большинства женщин как при вторичном, так и при первич-ном бесплодии. Причем в половине случаев от-сутствие БФ не было ассоциировано с низким пролиферативным ответом в СКЛ, отражающим сходство партнеров по HLA-антигенам [1,15]. Настоящая работа посвящена оценке влияния …”