Paternal Lymphocytes Research Articles

Intrauterine administration of paternal and maternal peripheral blood mononuclear cells mix as solution for repeated implantation failure.

To date, implantation is the rate-limiting step for the success of in vitro fertilization (IVF) treatment. Accumulating evidence suggests that immune cells contribute to embryo implantation, and several therapeutic approaches have been proposed for the treatment of recurrent implantation failure (RIF). Endometrial immune modulation with autologous activated peripheral blood mononuclear cells (PBMCs) is one of the most widely used protocols. However, the effect of intrauterine insemination of mixed paternal and maternal-activated PBMCs has not yet been attempted and studied. The aim of our study is to test the effect of the addition of paternal lymphocytes on the implantation rate in RIF patients. Mononuclear cells were isolated from the peripheral blood of 98 RIF patients and cultured for 72h before insemination into the endometrial cavity 48h before embryo transfer. Our patients were divided into 4 groups according to the type and number of PBMCs inseminations. Our study shows that activated PBMCs promoted clinical pregnancy rates (CPR) in all groups. Moreover, we found that the groups injected with more than 2 million cells showed a better clinical outcome and, more interestingly, patients inseminated with both paternal and maternal activated PBMCs showed the highest CPR, reaching 47.2%, in addition to the highest implantation rate 31. 2% and the live birth rate 41.39%. Our work demonstrates the importance of administering a large number of activated PBMCs with the addition of paternal activated PBMCs to immunomodulate the endometrium for the success of in vitro fertilization in RIF patients.

#216 : High Live Birth Rates After Low Dose Lymphocyte Immunization Therapy (LD-LIT) with Partner Lymphocytes in Recurrent Miscarriage Patients

Background and Aims: Recurrent Miscarriage (RM) affects 1–2% of couples trying to conceive, with 50% remaining unexplained. Meta-analyses suggest LIT improves pregnancy outcomes for RM couples. However, results are conflicting due to differing criteria and protocols. This study evaluates low dose LIT effectiveness in patients with unexplained RM and Th1/Th2/Treg paradigm disorders. Method: Self-controlled, prospective study of 23 RM patients receiving partner lymphocyte immunization from August 2021 to October 2022, with [Formula: see text]3 miscarriages less than 12 weeks when endometrium at ET was [Formula: see text]8mm and PGT embryos were used. Patients with abnormal Th1/Th2/Treg cell proportions and biomarkers were treated with paternal lymphocytes twice before embryo transfer (ET) and once post-pregnancy confirmation. Results: Significant decrease in Th1 and increase in Th2 cytokines like TNF-a and IFN-g and significantly increase in Treg cells and TGF-b noted and blocking antibodies detected in all patients after LIT therapy. 20/23 (87%) post LIT conceived and 4 delivered healthy full-term babies (17%) and 3 patients have yet to undergo ET. 48% (11/23) uneventful ongoing pregnancies crossed [Formula: see text]14 weeks. 3 patients had miscarriages (13%). 1 patient (4%) did not conceive. 1(4%) conceived spontaneously ([Formula: see text]25 wks) and 1(4%) opted to try to conceive naturally. Cumulative uneventful pregnancy outcome 65%. Conclusion: LIT was associated with high live birth rates, especially in women with RM. It not only ameliorates patient’s cellular immune function, but also further increases patient’s pregnancy success rate with high safety, which is worthy of clinical application and promotion. Being small size self-controlled study, this result needs to be validated with large we’ll planned RCTs. LIT may be considered a safe and effective treatment for RM/RIF in IVF patients in individual cases based on immunoprofiling (Th1/Th2/Treg paradigm disorders), after ruling out other potential causes of RM or RIF.

P-529 High Live Birth Rates After Low Dose Immunization Therapy (LIT) Pre and Post Pregnancy With Partner Lymphocytes In Patients With Recurrent Miscarriage (RM)

Abstract Study question Could Lymphocyte Immunization Therapy effectively improve pregnancy and live birth rate in Unexplained Recurrent Miscarriage patients? Summary answer The use of paternal lymphocytes pre and post pregnancy significantly increases the pregnancy success and Live Birth Rate In Patients With Recurrent Miscarriage (RM) What is known already RM affects 1–2% of couples who attempt to conceive and has been defined as three consecutive pregnancy losses within 20 weeks of pregnancy confirmation. Although many potential causes have been established for RM, about 50% of these remain idiopathic and unexplained owing to immunology factors. Meta-analyses have observed better effectiveness and safety of LIT in treating couples with RM shown improvement in pregnancy outcomes. Still, results are conflicting due to different screening criteria and therapeutic protocols. Objective of present study is to evaluate effectiveness of low dose LIT in patients with uRM and Th1/Th2/Treg paradigm disorders Study design, size, duration In self-controlled, prospective study, after IEC clearance and obtaining Informed consent, 19 RM patients underwent immunization with partner lymphocytes from August 2021 to October 2022. Inclusion criteria were at least three clinical pregnancies that culminated in abortion before 20 weeks of gestation or at least three cycles of IVF/ICSI with at least two PGT+ embryos and >8mm endometrium during ET and no pregnancy, normal coagulation tests, autoimmune antibodies negative, normal couple karyotyping. Participants/materials, setting, methods Maternal BMI of 30 and age of 45 was the upper limit with peripheral blood Th1/Th2/Treg cells proportions and concentrations of TNF-a, IFN-g, TGF-β1, IL-2, IL-4, IL-6, IL-10, and blocking antibodies were detected using flowcytometry/ELISA as per Seragen’s Immuno profiling platform. 30-50ml paternal blood was used to purify lymphocytes which were intradermally administered to the wife before Embryo Transfer and post-pregnancy confirmation. Main results and the role of chance Proportion of Th1 cells was significantly decreased while the proportions of Th2 cells and Treg cells were significantly increased in immunotherapy patients after treatment. In addition, the concentration of TGF-β1 in serum was significantly higher after immunotherapy than before. The concentration of TNF-a, IFN-g was significantly high before therapy were significantly decreased after therapy. LIT effectively induced the production of blocking antibodies in all the patients. 16/19 (84%) uRM patients underwent ET post LIT became pregnant and 4 of the pregnant patient had delivered healthy babies (21%). 42% (8/19) of patients have reported uneventful ongoing pregnancies crossed >14weeks. 4 patients who were pregnant for more than 12-14 weeks had miscarriages (21%). 1 patient (5%) did not conceive. 1 patient (5%) conceived spontaneously and crossed 20 weeks of uneventful gestation. 1 patient (5%) opted to try to conceive naturally hence ET is not planned. The cumulative positive uneventful pregnancy outcome was 68%, approximately the same as the figures reported earlier. LIT is associated with high live birth rates, especially in women with RM. It not only ameliorates patient’s cellular immune function but also further increases patient’s pregnancy success rate with high safety, which is worthy of clinical application and promotion. Limitations, reasons for caution This prospective self-control study with small sample size lacks randomized control group. Beneficial effects observed in this study are in sync with published data. Larger study with patients recruited based on inclusion criteria of unexplained recurrent miscarriage due to immunological factors is proposed for recommending LIT as routine therapy. Wider implications of the findings Our study findings supports LIT as a beneficial treatment for RM/RIF in IVF patients. LIT may be considered safe and effective therapy in individual cases and based on the immunoprofiling (Th1/Th2/Treg paradigm disorders), after all other potential causes of RM or RIF have been ruled out. Trial registration number Not applicable

The Effectiveness of Paternal Lymphocyte Immunotherapy for Recurrent Miscarriage in Couples with Human Leukocyte Antigen Sharing: A Novel Approach

Background: The aetiology of recurrent pregnancy loss (RPL) is varied and ranges from genetic abnormalities, autoimmune, uterine structural abnormalities, thrombophilic disorders, endocrinologic dysfunction, infective to idiopathic factors. Reproductive immunology may provide an area of opportunity in treatment of idiopathic cases. Research has indicated that any amount of HLA compatibility among spouses leads to immunological perturbations leading to higher RPL rates. These disturbances in alloimmune parameters are found to be significantly reduced after a successful immunotherapy with paternal lymphocytes immunotherapy (LIT) among couples who share HLA. Aim: To analyze the role of alloimmune factors in couples who are considered unexplained RPL by testing HLA sharing between the partners and to determine the effect of lymphocyte immunotherapy (LIT) on live birth rate in couples with HLA sharing. Methods: This retrospective observational study was conducted in a single tertiary center in Bangalore for a duration of three years. Couples who satisfied the inclusion and exclusion criteria were selected and HLA sharing between the partners was tested. Couples with HLA sharing received LIT before and during pregnancy. The pregnancy and live birth rates were calculated and compared with couples with HLA sharing who did not receive LIT. Results: Out of the 199 couples who were screened for HLA sharing among partners, 146 couples had different degrees of HLA sharing. 81 couples received LIT and 32 did not opt for LIT and were taken as control group. The pregnancy and live birth rates were significantly higher in the LIT group compared to control group (77.7% vs 40.6%, p-0.0001, OR 5.1, 95% CI 2.10-11.4 and 56.7% vs 21.8%, p-0.0002, OR 4.6, 95% CI 2.13-13.8 respectively). Miscarriage rates were similar between the two groups. Conclusion: Partner lymphocyte immunotherapy is a novel treatment option in improving the pregnancy outcomes among women with unexplained RPL and HLA sharing among partners.

Efficacy of lymphocyte immunotherapy in the treatment of recurrent pregnancy loss from alloimmunity: A systematic review and meta-analysis.

The efficacy of lymphocyte immunotherapy (LIT) in the treatment of recurrent pregnancy loss (RPL) from alloimmunity has been debated for years. There is conflicting evidence on the therapeutic role of LIT, since the etiology of most cases of RPL is previously classified as idiopathic. A systematic search of PubMed and Cochrane databases was done for randomized controlled trials that assessed the efficacy of paternal lymphocyte or third donor LIT among patients with primary or secondary RPL. The primary outcome was live birth rate after LIT. Random-effect meta-analysis was conducted using the software RevMan 5.4. Pre-planned subgroup analyses of source of lymphocytes, timing and frequency of administration, and concentration per immunization dose were conducted. Data from eight trials showed a statistically significant benefit of LIT (RR=1.45, 95% CI 1.05-2.01). The overall live birth rate is higher in the treatment group (65.6%) compared to placebo or no treatment (45.2%). Subgroup analysis based on source of lymphocytes revealed a trend towards benefit with paternal LIT but with wide confidence interval (RR=1.34, 95% CI=.84-2.14). Multiple doses of immunotherapy before pregnancy and low dose (5×106 cells) LIT showed significant benefit. Sensitivity analysis involving studies with a low risk of bias demonstrated significant benefit of increased live birth rate among patients treated with LIT compared to those who received placebo or no treatment (RR=1.97, 95% CI=1.53-2.53). LIT demonstrate benefit in improving pregnancy outcome of patients with RPL from alloimmunity.

Live Birth Rates after Active Immunization with Partner Lymphocytes.

Although many potential causes have been established for recurrent implantation failure (RIF) and recurrent miscarriage (RM), about 50% of these remain idiopathic. Scientific research is focused on immunological risk factors. In the present study, we aim to evaluate live birth rates after immunization with paternal lymphocytes (lymphocyte immunotherapy (LIT)). This retrospective study consisted of 148 couples with a history of RM and/or RIF. The women underwent immunization with lymphocytes of their respective partners from November 2017 to August 2019. Fifty-five patients (43%) had live births. Stratified by indication (RM, RIF, combined), live birth rates in the RM and the combined group were significantly higher than that in the RIF group (53%, 59% and 33%, respectively, p = 0.02). The difference was especially noticeable during the first 90 days after immunization (conception rate leading to live births: 31%, 23% and 8% for RM, the combined group and RIF, respectively; p = 0.005), while there was no difference between groups during the later follow-up. LIT was associated with high live birth rates, especially in women with recurrent miscarriage. In view of the limited data from randomized studies, LIT cannot be recommended as routine therapy. However, it may be considered in individual cases.

Association of CD200 expression in paternal lymphocytes with female Th1/Th2 balance and pregnancy establishment at immunotherapy of recurrent spontaneous abortion

We hypothesized that expression of transmembrane glycoprotein CD200 on paternal lymphocytes used for pre-gestational lymphocyte immunotherapy (LIT) of recurrent spontaneous abortion (RSA) can suppress the pro-inflammatory Th1-type immunity required for successful implantation. To reveal the association between CD200 expression, female immune background after LIT, and pregnancy establishment, we have performed this work. Pre-gestational alloimmunizations were given to 37 women using paternal peripheral blood leukocytes, combined with additional alloimmunizations in case of pregnancy. Lymphocyte phenotypes were determined by flow cytometry. Cytokines produced by mitogen-stimulated female peripheral blood cells were estimated by FlowCytomix™ technology. We have shown that 78.4% (29/37) of women became pregnant within 12 menstrual cycles after pre-gestational LIT. Pregnancy establishment depends on the intensity of CD200 expression, which is significantly higher on the CD200+ lymphocytes administered to women who later did not achieve pregnancy (P<.05). The expression of CD200 negatively correlates with the ratios of Th1/Th2 cytokines produced by female peripheral blood cells (P<.05) and positively correlates with the frequency of female circulating regulatory T cells after LIT (P<.05). The ROC analysis showed that the intensity of CD200 expression and the Th1/Th2 ratios are the significant predictors of pregnancy establishment after pre-gestational LIT (P<.05 and P<.01, respectively). Elevated CD200 expression on allogeneic lymphocytes most likely suppresses the pro-inflammatory Th1-type immunity needed for successful embryo implantation. Therefore, a personalized approach of LIT should be applied to avoid negative effects of such immunomodulation on pregnancy establishment.

Gestational and perinatal outcomes in recurrent miscarriages couples treated with lymphocyte immunotherapy.

ObjectiveThis study aims to elucidate which types of recurrent miscarriage (RM) patients experienced a livebirth after paternal lymphocyte immunotherapy (LIT) and to evaluate the perinatal outcome.Study designRetrospective analysis of a multicenter, observational study which enrolled 1096 couples with a history of two or more spontaneous miscarriages without any intercalated delivery. We conducted an intention-to-treat analysis of couples with RM treated with or without LIT regarding to gestational and perinatal outcomes. We compared groups by using the Student’s t-test or Kruskal–Wallis test, Fisher’s exact-test and χ2 test when appropriate.ResultsThe success of gestation was significantly higher in the LIT group (60.1% vs. 33.1%; p < 0.001). A sub-analysis of four different immune disorder groups revealed a significantly higher success in the LIT group in all immune categories, except in patients who had autoantibodies positive. We observed no significant differences in perinatal outcomes such as gestational age at birth, preterm and extreme preterm birth, and birth weight in successful pregnancy in both groups. The success rate was significantly higher when LIT was administrated before and during pregnancy and only during pregnancy compared to only before pregnancy (p < 0.01).ConclusionsCareful laboratory test phenotyping of RM patients may identify subgroups most likely to benefit and exclude those with little likelihood of benefit, and LIT during a pregnancy may significantly improve success rates.

Expression of Early Activation Marker CD69 on Peripheral Blood Lymphocytes from Pregnant Women after First Trimester Alloimmunization.

We studied the expression of an early activation marker CD69 in peripheral blood lymphocytes of pregnant women with a history of recurrent pregnancy loss after immunization with paternal lymphocytes. Spontaneous and phytohemagglutinin-stimulated expression of CD69 on the surface of T cells and NK cells isolated from the peripheral blood was analyzed. On gestation week 5-6, the number of T cells expressing CD69 spontaneously and after stimulation was significantly higher in women with miscarriage than in woman with prolonged pregnancy. However, the number of cells with CD56(+) phenotype expressing CD69 did not differ in these groups. No differences were found in the number of cells of all subpopulations expressing CD69 after stimulation on gestation week 12 in woman with full-term current pregnancy and in woman with physiological pregnancy.

The efficacy of paternal lymphocytes immunizations in patients with recurrent miscarriages and the presence of autoantibodies

The efficacy of paternal lymphocytes immunizations in patients with recurrent miscarriages and the presence of autoantibodies

The efficacy of paternal lymphocytes immunizations in patients with recurrent miscarriages and the presence of autoantibodies

The efficacy of paternal lymphocytes immunizations in patients with recurrent miscarriages and the presence of autoantibodies

Altered Th17/Treg Ratio in Recurrent Miscarriage after Treatment with Paternal Lymphocytes and Vitamin D3: a Double-Blind Placebo-Controlled Study.

Recurrent miscarriage (RM) affects 2-5% of pregnant women. Paternal lymphocyte immunotherapy is a common treatment for RM patients but the outcome has not been consistent. Therefore, combined therapy with other immunosuppressive drugs such as 1a, 25-dihydroxy-vitamin-D3 (vitamin D3) may improve the outcome. To investigate the effect of vitamin D3 on the balance of two essential T cells subsets, T helper (Th) 17 and T regulatory (Treg) cells, which contribute to the immune tolerance during pregnancy. The expression levels of CD4 and forkhead box protein 3 (FOXP3) in Treg cells, and the expression levels of CD4 and IL-17 in Th17 cells, were evaluated pre- and 3 months post-immunotherapy in RM patients treated with a combination of paternal lymphocytes and vitamin D3 compared with RM patients receiving lymphocyte immunotherapy alone. Vitamin D3 therapy decreased the frequency of Th17 cells in addition to reducing the Th17/Treg ratio in peripheral blood of RM patients compared with the control group (p<0.05). Considering that RM patients have a higher Th17/Treg ratio in peripheral blood, vitamin D3 may be a candidate therapeutic approach in this disease.

Paternal lymphocyte immunization in women with recurrent embryo implantation failures and/or recurrent miscarriages after IVF

as in the 1st trimester trophoblast cell line HTR-8/SVneo. Isolated blood monocytes where cultured and differentiated in the presence of IL-34 for six days. When analyzed with flow cytometry, they showed high expression of CD14, CD163 (scavenger receptor), CD206 (mannose receptor) and CD209 (DC-SIGN), markers expressed on decidual macrophages. Taken together, our results show that IL-34 is produced both by placental and decidual cells and is able to induce macrophages with a phenotype resembling that of decidual macrophages. The findings suggest a role for IL-34 in the regulation of decidual macrophages during early pregnancy.

Immunomodulatory and clinical effects of the "tiaomian III decoction" in patients with blood blocking antibody deficiency and recurrent spontaneous abortion.

We studied the immunomodulatory and clinical effects of the empirical formula "tiaomian III decoction" on maternal blood blocking antibody deficiency and recurrent spontaneous abortion. Sixty-one patients with blocking antibody deficiency were divided in the experimental group (N = 31), who took tiaomian III decoction, and the control group (N = 30), who received active immunotherapy with paternal lymphocytes; both treatments lasted 3 months. Blocking antibodies, anti-idiotypic antibodies, interleukin, T-lymphocyte subsets, and macrophage colony-stimulating factor (M-CSF) were tested. After treatment, the positive conversion rate reached 87.1 and 86.7% in the experimental and control groups, respectively. After treatment, CD4 levels decreased while CD8 levels increased in both groups. The CD4/CD8 ratio was higher than normal and increased significantly from pre-treatment (P < 0.05). IL-10 and M-CSF levels increased significantly in both groups (P < 0.05). The 1-year conception rates of the experimental and control groups were 58.1 and 46.7%, respectively (P < 0.05). The results show the tiaomian III decoction can increase the positive conversion rate of maternal blocking antibodies and promote the production of IL-10 and M-CSF. Thus, it strengthens the maternal body's protection of the fetus and maintenance of conception. The higher conception rate of the experimental group demonstrates the positive clinic efficacy of the tiaomian III decoction on maternal blood blocking antibody deficiency and recurrent spontaneous abortion.

Flow cytometry crossmatch in women undergoing paternal lymphocyte immunization: correlation between fluorescence intensity and pregnancy outcome

Introduction: The success of a pregnancy depends on alloimmune mechanisms, with the allogeneic fetus being considered a successful allograft. Immunizationwith paternal lymphocytes has been shown to be an effective therapeutic option for cases of recurrent pregnancy loss (RPL). Currently, flow cytometry cross-match (FCXM) is used to evaluate patients with RPL. Objectives: To evaluate the results of FCXM in women with a history of RPL who conceived following paternal lymphocyte immunization (PLI), and correlate them with pregnancy outcome. Materials and methods: Eighty-five patients were selected for the study based on the following inclusion criteria: ≥2 RPL, initial FCXM negative against the father, and women with primary RPL. The women were divided into two groups: successful pregnancy outcome and pregnancy loss. After an initial negative FCXM (baseline), the patients were immunized with doses of PLI and 30 days after the final PLI a second FCXM was performed. Median fluorescence intensity (MFI) was calculated at both time points and the two groups were compared. Results: Evaluation ofMFI ratio (following PLI/baseline) for T and B lymphocytes showed no statistically significant differences between the two groups (p=0.119 for T lymphocytes and p=0.109 for B lymphocytes). Conclusion: There was no difference between the two groups regarding median fluorescence intensity ratio (following PLI/baseline) for T and B lymphocytes. Therefore, themedianfluorescence intensity ratio for T andB lymphocytes cannot be used as a laboratory parameter to evaluate the success of PLI with respect to pregnancy outcome following immunotherapy.

The impact of antinuclear antibodies on paternal lymphocyte immunization in women with recurrent miscarriage outcome

Karin Malickova1,∗, Michal Koucký2, Antonin Pařizek2, Květa Pelinkova1, Helena Brodska1, Zdeněk Hajek2, Anna Germanova2, Oto Mestek3, Tomas Zima1 1 Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and 1st Faculty of Medicine of Charles University in Prague, Czech Republic 2 Department of Gynecology and Obstetrics, General University Hospital and 1st Faculty of Medicine of Charles University in Prague, Czech Republic 3 Institute of Chemical Technology Prague, Czech Republic

Characteristics of immune cell changes before and after immunotherapy and their clinical significance in patients with unexplained recurrent spontaneous abortion

To investigate the characteristics of immune cells before and after immunotherapy and their clinical significance in patients with unexplained recurrent spontaneous abortion (URSA), an analysis of 67 URSA patients, 67 sporadic spontaneous abortion (SA) patients, and 22 normal nonpregnant women (as controls) was conducted. URSA patients underwent immunotherapy using paternal lymphocytes. Peripheral blood from patients and controls was examined for lymphocytes and other markers of immune status. Before the immunotherapy, lymphocyte counts, CD4:CD8 cell ratios, and the relative proportion of natural killer (NK) cells were significantly higher in the URSA patient group than in the SA patient and control groups (P < 0.05). After the therapy, all of these three measures were decreased, whereas the percentage of T cells was increased, and statistically significant differences before and after the immunotherapy were detected (P < 0.05). Therefore, the immune system appears to be activated in the URSA patients, and the abnormal immunologic state in the URSA patients is more severe than in the SA patients. The alterations in T and NK cells may be involved in the etiopathogenesis of URSA. Lymphocyte immunotherapy appears to be an effective treatment for URSA patients.

Study on positive rate of blocking antibody in women with recurrent spontaneous abortion administered by route and frequency of paternal lymphocyte immunotherapy

To investigates factors affecting the positive rate of blocking antibody treated by paternal lymphocyte immunotherapy in patients with recurrent spontaneous abortion (RSA). From January 2008 to August 2012, 326 RSA cases undergoing treatment in Infertility Center of Qilu Hospital were studied retrospectively. Those patients were divided into 2 groups randomly: 260 cases in intradermal injection group were administered via bilateral forearm intradermal injections for immunotherapy once 21 days, then the blocking antibody was determined after 2 (23 cases) , 3(73 cases), 4 (74 cases) , 5(90 cases) times respectively, while in subcutaneous injection group, the 66 cases were administered via subcutaneous injection once 21 days, the blocking antibody measured after 3 times; In both cases, the blocking antibody was all determined 2 weeks later. The positive rate of blocking antibodies and the rate of successful pregnancy was recorded, and then followed up after the blocking antibody turning positive. (1) Positive rate of blocking antibodies:the positive rate of blocking antibodies were 17% (4/23) , 58% (42/73), 72% (53/74) and 84% (76/90) in the 2, 3, 4, and 5 times of intradermal injection group, respectively (P < 0.05). In subcutaneous injection group, the positive rate of blocking antibodies was 38 % (25/66), which was significantly lower than that in group intradermal injection receiving 3 times immunotherapy (P < 0.05). (2) The rate of pregnancy:the 176 patients out of 200 patients were pregnant when antibody was positive after immunotherapy, with 71.6% (126/176) of patients gained successful pregnancy(the length of pregnancy more than 5 months). The route and frequency of administration of immunotherapy could influence the positive rate of blocking antibody. The rate of successful pregnancy will be increased after blocking antibody turning positive.

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

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.

Correlation between serum zinc levels and successful immunotherapy in recurrent spontaneous abortion patients

BACKGROUND:Immunotherapy with paternal lymphocytes plays an important role in preventing recurrent spontaneous abortion (RSA) and is an effective treatment for it. This kind of treatment is performed as an immunotherapy method in several centers in the world. It attributes to the production of anti-paternal cytotoxic antibodies (APCAs) in women with RSA. Production of APCA after lymphocyte immunotherapy (LIT) in RSA patients gives them a better chance for successful pregnancy. Regarding the important effect of trace elements on the function of the immune system, we tried to investigate the correlation between serum zinc level and the success of LIT in RSA.MATERIALS AND METHODS:Serum zinc concentration was determined in two groups of RSA patients using atomic absorption spectrophotometer systems. Group (a) that responded to the paternal lymphocytes and their cross-match test was positive, and group (b) that had no response to the paternal lymphocytes immunizations and their cross-match test was negative.RESULTS:Serum zinc levels in group (a) patients were 74.98 ± 11.88 μg/dl, which was significantly higher than those in group (b) with the zinc concentration of 64.22 ± 9.22 μg/dl.CONCLUSIONS:Zinc deficiency may be one of the substantial causes of negative results for LIT in RSA patients. Therefore, compensation of zinc defect before LIT can be a promising approach to improve the immune response in patients.