Immunotherapy For Recurrent Spontaneous Abortion Research Articles

A comprehensive Bayesian analysis assessing the effectiveness of lymphocyte immunotherapy for recurrent spontaneous abortion

AbstractRecurrent spontaneous abortion (RSA) affects 2%–5% of couples worldwide and remains a subject of debate regarding the effectiveness of lymphocyte immunotherapy (LIT) due to limited retrospective studies. We conducted a comprehensive Bayesian analysis to assess the impact of LIT on RSA. Using data from the Shenzhen Maternity and Child Healthcare Hospital (2001–2020, n = 2316), a Bayesian generalized linear model with predictive projection feature selection was employed. Our analysis revealed a significant improvement in live birth rates for RSA patients undergoing LIT. Notably, LIT had a greater impact compared to the other 85 factors considered. To mitigate research bias, we conducted a Bayesian meta-analysis combining our dataset with 19 previously reported studies (1985–2021, n = 4246). Additionally, we developed an empirical model highlighting the four key factors, which are the LIT result, age, paternal blood type, and anticardiolipin antibody. Younger age (19–27), paternal blood type B, and a positive anticardiolipin antibody (IgM) were associated with better therapeutic outcomes in LIT for RSA. These findings aid clinicians in identifying suitable candidates for LIT and improving treatment outcomes.

Am J Reprod Immunol 2007; 57: 167‐168. Neonatal Thrombocytopenia As Side Effect of Immunotherapy for Recurrent Spontaneous Abortion

Am J Reprod Immunol 2007; 57: 167‐168. Neonatal Thrombocytopenia As Side Effect of Immunotherapy for Recurrent Spontaneous Abortion

Neonatal Thrombocytopenia As Side Effect of Immunotherapy for Recurrent Spontaneous Abortion

American Journal of Reproductive ImmunologyVolume 57, Issue 3 p. 167-168 Neonatal Thrombocytopenia As Side Effect of Immunotherapy for Recurrent Spontaneous Abortion Correction(s) for this article Am J Reprod Immunol 2007; 57: 167-168. Neonatal Thrombocytopenia As Side Effect of Immunotherapy for Recurrent Spontaneous Abortion Volume 57Issue 4American Journal of Reproductive Immunology pages: 302-302 First Published online: March 13, 2007 Aristidis Deligiannidis, Aristidis Deligiannidis Immunology Department and National Peripheral Histocompatibility Center, Hippokration Hospital, Thessaloniki, Greece;Search for more papers by this authorEfthimia Parapanissiou, Efthimia Parapanissiou Immunology Department and National Peripheral Histocompatibility Center, Hippokration Hospital, Thessaloniki, Greece;Search for more papers by this authorAntigoni Mavroudi, Antigoni Mavroudi Third Clinic of Paedatrics, Hippokration Hospital, Thessaloniki, GreeceSearch for more papers by this authorTheodouli Papastavrou, Theodouli Papastavrou Third Clinic of Paedatrics, Hippokration Hospital, Thessaloniki, GreeceSearch for more papers by this author Aristidis Deligiannidis, Aristidis Deligiannidis Immunology Department and National Peripheral Histocompatibility Center, Hippokration Hospital, Thessaloniki, Greece;Search for more papers by this authorEfthimia Parapanissiou, Efthimia Parapanissiou Immunology Department and National Peripheral Histocompatibility Center, Hippokration Hospital, Thessaloniki, Greece;Search for more papers by this authorAntigoni Mavroudi, Antigoni Mavroudi Third Clinic of Paedatrics, Hippokration Hospital, Thessaloniki, GreeceSearch for more papers by this authorTheodouli Papastavrou, Theodouli Papastavrou Third Clinic of Paedatrics, Hippokration Hospital, Thessaloniki, GreeceSearch for more papers by this author First published: 07 February 2007 https://doi.org/10.1111/j.1600-0897.2006.00464.xCitations: 3 Efthimisa Parapanissiou, Immunology Department and National Peripheral Histocompatibility Center, 49 Konstantinoupoleos Str., Thessaloniki 546 42, Greece.E-mail: efipara@yahoo.com Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume57, Issue3March 2007Pages 167-168 RelatedInformation

Should we re-examine the status of lymphocyte alloimmunization therapy for recurrent spontaneous abortion?

In the human, lymphocyte alloimmunization immunotherapy (IT) has been proposed as a treatment for recurrent spontaneous abortion (RSA). This treatment has been the subject of debate for a long period of time. Recently, it has been proposed to extend such a treatment for implantation failure in humans, and I was asked to express my opinion on this topic. I reviewed the evolution and theories and current paradigms in Reproductive Immunology and rationales proposed for IT. New discoveries show the complexity of implantation as a step by step developmental event, in mice and humans, and as such led me to re-examine paradigms currently evoked for extension of IT to implantation. Such a re-examination obviously leads me to re-question the basis of IT for RSA itself. I conclude that the Th1/Th2 paradigm, evoked as the current basis for IT, and as useful as it has been to explain pregnancy, is no longer sufficient. It is especially insufficient to explain the process of implantation, which involves inflammatory molecules and cannot fit in such a scheme. It ensues that alloimmunization has no scientific rationale for the treatment of human implantation as a whole, and should not be applied broadly at such a stage of pregnancy. Furthermore, its use in RSA should be re-examined.

Assessing human alloimmunization as a strategy for inducing HIV type 1 neutralizing anti-HLA responses.

Xenovaccination of rhesus macaques with human HLA Class I and II proteins has been demonstrated to elicit protective immunity against challenge with SIV grown in human cells. To determine if alloimmunization in humans could lead to protective immunity against HIV-1, we prospectively followed a small group of women receiving whole-cell alloimmunization in the form of leukocyte immunotherapy for recurrent spontaneous abortion. Whole-cell vaccine recipients and their respective partners (referred to as donors) provided pre- and postimmune blood samples for analysis. Study participants were HLA typed by sequence-specific PCR and antibodies specific for HLA Class I and II antigens were measured in recipient plasma. To determine if anti-HLA antibody responses detected in recipient plasma samples were capable of neutralizing HIV-1 in vitro, we grew laboratory strain HIV-1(IIIB) and primary isolate HIV-1(301660) in donor-derived CD4(+) T lymphocytes. The ability of purified whole IgG from responding patients to neutralizing infectivity of the respective donor-derived virus was then assayed in vitro. All donor-recipient pairs were determined to be HLA discordant for at least one Class I and one Class II locus. Two of seven female recipients in total made strong anti-HLA antibody responses specific to the HLA haplotype of the male donor in response to the alloimmunization regimen. For one recipient, IgG antibodies specific for donor HLA Class I and II antigens were able to neutralize both HIV-1(IIIB) and a primary isolate HIV-1(301660). In addition polyclonal anti-HLA class II antibodies against a single determinant (DR4) of this donor were also neutralizing. In contrast, the other recipient exhibiting antibodies only against donor HLA Class I antigens did not neutralize HIV-1(IIIB). Using samples from a small number of women undergoing leukocyte immunotherapy, we have demonstrated for the first time that allele-specific anti-HLA antibodies elicited through human alloimmunization are capable of neutralizing HIV-1 in vitro.

Possible mechanisms of immunotherapy for maintaining pregnancy in recurrent spontaneous aborters: analysis of anti-idiotypic antibodies directed against autologous T-cell receptors.

We examined whether immunotherapy for recurrent spontaneous abortion (RSA) using paternal lymphocytes induces anti-T-cell receptor (TCR) idiotypic antibodies in RSA patients. The sera of these patients were assessed for inhibitory activity against mixed lymphocyte reactions (MLR) between maternal responder cells and paternal stimulator cells. Sera of four of the five women who maintained pregnancy successfully after immunotherapy showed significant MLR inhibition, whereas none of the five women who had unsuccessful pregnancies showed significant MLR inhibition. These sera inhibited the MLR of autologous responder T-cells, when stimulated with lymphocytes having the same HLA-DR antigens as the patient's husband, but not when stimulated with lymphocytes having unrelated HLA-DR antigens. This MLR inhibitory activity was absorbed by autologous maternal T-lymphoblasts induced by stimulation with lymphocytes having the paternal HLA-DR type but not by those induced by stimulation with lymphocytes having other HLA-DR types. The maternal serum inhibited the proliferation of autologous T-cells, but not of non-autologous T-cells, stimulated with paternal lymphocytes. These results indicate that anti-TCR idiotypic antibodies were induced in RSA patients by immunotherapy. These antibodies may contribute to maintaining pregnancy by negatively regulating maternal T-cells directed against HLA-DR antigens of the fetus.

Hard Science Versus Phenomenology in Reproductive Immunology

It has been suggested that studies of immunological aspects of reproduction have recently changed from the phenomenological (e.g., speculative/descriptive) to hard science (e.g., precise molecular description/ explanation). The significance of this development is explored by analysis of the contribution made by hard science that has led to a number of assertions. Does HLA-G determine maternal tolerance of her semi-allogeneic fetus? Do differences in placentation between humans, rodents, and other species make direct comparisons largely meaningless? Does membrane cofactor protein (CD46) contribute to pregnancy success by protecting sperm and fetal trophoblast from complement-mediated lysis? Does a low frequency in mice of maternal T cells specific for paternal alloantigens occur, and if so, does phenomenon explain specific maternal tolerance in pregnancy? Do placental and decidual macrophage components provide an important immediate antigen-nonspecific host defense to infection? Does the mix of bioactive molecules make the uterus an immunologically privileged site, and does the molecular melange have a pivotal role in promoting growth and development of the placenta and embryo? Does prolactin acting on receptors on lymphocytes suppress function and thereby account for remission of autoimmune disease in pregnant women? Is the efficacy and safety of immunotherapy for recurrent spontaneous abortion a thorny issue that will be resolved by an ongoing funded national trial? What is a scientifically correct timeline of important discoveries and developments in reproductive immunology? It is argued that it is unprofitable to divorce phenomenology from hard science and that the timeline for developments in reproductive immunology begin with Darwin. Irrespective of whether one is dealing with phenomena or hard science data, Hippocrates was correct in his aphorism that "description is infinite and easy; explanation is limited and difficult".

IMMUNOTHERAPY FOR RECURRENT SPONTANEOUS ABORTION: ANALYSIS 2

American Journal of Reproductive ImmunologyVolume 32, Issue 4 p. 279-280 IMMUNOTHERAPY FOR RECURRENT SPONTANEOUS ABORTION: ANALYSIS 2 James R. Scott MD, Corresponding Author James R. Scott MD Professor and Chairman Professor and Chairman, Department of Obstetrics and Gynecology, University of Utah Medical Center, 50 North Medical Drive, Salt Lake City, UT 84132.Department of Obstetrics and Gynecology, University of Utah Medical Center, 50 North Medical Drive, Salt Lake City, UT 84132.Search for more papers by this author James R. Scott MD, Corresponding Author James R. Scott MD Professor and Chairman Professor and Chairman, Department of Obstetrics and Gynecology, University of Utah Medical Center, 50 North Medical Drive, Salt Lake City, UT 84132.Department of Obstetrics and Gynecology, University of Utah Medical Center, 50 North Medical Drive, Salt Lake City, UT 84132.Search for more papers by this author First published: December 1994 https://doi.org/10.1111/j.1600-0897.1994.tb01125.xCitations: 4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume32, Issue4December 1994Pages 279-280 RelatedInformation

The Recurrent Miscarriage Immunotherapy Trialists Group. Worldwide Collaborative Observational Study and Meta‐Analysis on Allogenic Leukocyte Immunotherapy for Recurrent Spontaneous Abortion (Am J Reprod Immunol. 1994; 32:55–72)

The Recurrent Miscarriage Immunotherapy Trialists Group. Worldwide Collaborative Observational Study and Meta‐Analysis on Allogenic Leukocyte Immunotherapy for Recurrent Spontaneous Abortion (<i>Am J Reprod Immunol</i>. 1994; 32:55–72)

Worldwide Collaborative Observational Study and Meta‐Analysis on Allogenic Leukocyte Immunotherapy for Recurrent Spontaneous Abortion1

PROBLEM: Recurrent spontaneous abortion (RSA) is a common complication of pregnancy for which there is no known cure. Therefore, effective treatment is needed. Published results from controlled clinical trials of allogeneic leukocyte immunization of women suffering from RSA have given conflicting results. To address this controversy, the international raw data of all patients who had been entered into clinical trials that included a control group were collected and analyzed. The primary question to be answered was whether alloimmune stimulation of the female partner improves the subsequent live birth rate.METHODS: Fifteen clinical centers were identified worldwide because they controlled appropriate raw data. Consequently, nine randomized trials (seven double‐blinded) were evaluated independently by two separate data analysis teams to assure conclusions were robust. One team also compared randomized trials to the results of six nonrandomized cohort‐controlled studies to test for bias in nonrandomized trials. Factors predicting successful live births among couples with RSA were evaluated by logistic regression.RESULTS: Although the two independent analyses made use of different definitions and utilized different statistical methods, the results of both were similar. The live birth ratios (ratio of live births in treatment and control groups) with 95% confidence intervals (CI) were 1.16 (CI, 1.01‐1.34, P = 0.031) and 1.21 (CI, 1.04‐1.37, P = 0.024), respectively. The absolute differences in live birth rates between treatment and control groups were 8% and 10% in respective analyses. Results in randomized and nonrandomized trials were surprisingly similar despite significant differences in composition of control and treatment groups. Live birth rates were lower with older female partners, more than five abortions, with a positive ANA or with positive anticardiolipin antibodies. Live birth rates were higher if the female partner had prior to treatment serum antibodies to paternal leukocytes or converted from negative to positive with immunization. Approximately 0.5% of controls and 2.1% of treated patients experience side effects for a 1.6% treatment related effect. There was no evidence of an increased risk of adverse effects on the fetus.CONCLUSIONS: Two independent analyses of worldwide data on allogeneic leukocyte immunization for treatment of RSA suggest that alloimmunization may be an effective treatment. The treatment effect appears, however, to be small, and the data indicate that immunotherapy helps only 8% to 10% of affected couples. A current lack of diagnostic tests defining patients who most likely would benefit from immunotherapy, precludes the identification of a patient population that would benefit most from such treatment. The efficacy of treatment in such a subgroup could be expected to increase and could be of sufficient magnitude to allow the determination of more effective immunization protocols. This study does not exclude the possibility of a partial correction of a widely prevalent immunology defect by immunotherapy. The presence of such a defect would indicate a need for more effective therapy. The unexplained variation in pregnancy success rates of control groups among centers continues to present a statistical problem, limiting the statistical evaluation of retroactively obtained data.

Flow cytometric crossmatch and early pregnancy loss in women with a history of recurrent spontaneous abortions who underwent paternal leukocyte immunotherapy

The purpose of our study was to evaluate the clinical significance of flow cytometric crossmatch in managing women with unexplained recurrent spontaneous abortions who have been immunized with paternal leukocytes. Two-color flow cytometric crossmatch was performed after immunotherapy in 69 women with recurrent spontaneous abortions to detect maternal immunoglobulin G antibodies against paternal T lymphocytes. A positive flow cytometric crossmatch was determined by a > or = 20 channel increases (256 channel linear scale-log amplification) in the fluorescence intensity of the T-cell peak. We analyzed the clinical correlation between flow cytometric crossmatch results and subsequent pregnancy outcome in those patients using the Fisher exact test. In 46 subsequent pregnancies among 69 immunized women the incidence of early subsequent pregnancy wastage was only 6 (17.1%) of 35 in flow cytometric crossmatch-positive patients and 7 (63.6%) of 11 in flow cytometric crossmatch-negative patients (p < 0.01). These data indicate that a two-color T cell flow cytometric crossmatch predicts subsequent pregnancy outcome in patients undergoing immunotherapy for recurrent spontaneous abortion.

Immunotherapy for Recurrent Spontaneous Abortion and its Analogies to Treatment for Cancer

American Journal of Reproductive ImmunologyVolume 25, Issue 3 p. 114-119 Immunotherapy for Recurrent Spontaneous Abortion and its Analogies to Treatment for Cancer C.B. COULAM, Corresponding Author C.B. COULAM Center for Reproduction and Transportation Immunology, IndianapolisCenter for Reproduction and Transplantation Immunology, 1701 North Senate Blvd., Indianapolis, IN 46202.Search for more papers by this authorW.P. FAULK, W.P. FAULK Center for Reproduction and Transportation Immunology, IndianapolisSearch for more papers by this authorJ.A. MCINTYRE, J.A. MCINTYRE Center for Reproduction and Transportation Immunology, IndianapolisSearch for more papers by this author C.B. COULAM, Corresponding Author C.B. COULAM Center for Reproduction and Transportation Immunology, IndianapolisCenter for Reproduction and Transplantation Immunology, 1701 North Senate Blvd., Indianapolis, IN 46202.Search for more papers by this authorW.P. FAULK, W.P. FAULK Center for Reproduction and Transportation Immunology, IndianapolisSearch for more papers by this authorJ.A. MCINTYRE, J.A. MCINTYRE Center for Reproduction and Transportation Immunology, IndianapolisSearch for more papers by this author First published: April 1991 https://doi.org/10.1111/j.1600-0897.1991.tb01077.xCitations: 11AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume25, Issue3April 1991Pages 114-119 RelatedInformation