Lymphocyte Immunization Therapy (LIT) in Reproductive Failures: New Horizons

Description

Recurrent Miscarriages (RM) & Implantation Failure (IF) have remained an enigma to clinicians and researchers. Even after ruling out all possible causative factors, 50-60% cases still remain “Unexplained’. A majority of these so called “Unexplained” cases are now found to have immunological basis.This book is going into the Immunological aspects of these clinical dilemmas, demystifying the role of Immunology and Immunotherapy in RM and IF. The authors have been working in the field of Reproductive Immunology and Immunotherapy for the last 25 years and they have come out with this book combining the international studies with their own experience. The purpose of writing this book is to provide a comprehensive treatise about Immunotherapy, so that it can become an acceptable modality of treatment in cases where it is needed and is effective.The book discusses the basics in Reproductive Immunology. The immunological changes occurring during pregnancy, the role of Cell mediated Immunity (T cells), Humoral Immunity including cytokines is explained. The normal immunological mechanisms protecting the embryo are highlighted and how these mechanisms are disturbed leading to RM and IF, is also explained.The first and the most discussed method of Immunotherapy is Lymphocyte Immunization Therapy (LIT). The book has given a complete overview of LIT, describing how it created euphoria when it was first introduced, how it gradually went into disrepute and how it is now making a comeback. As the authors have personal experience of LIT, the book gives a detailed and complete information about this active form of immunotherapy.The book has a special section on case studies where the authors have given some clinical case reports (including some of their own), who were treated for immunological factor in RM/IF and were treated with Immunotherapy. These cases can be a useful guide to the readers.The book will be useful not only for undergraduate and postgraduate students but also for clinicians in their practice and for researchers for review of developments in the field. Preface Acknowledgments Contents About the Authors Part I: Reproductive Immunology and Reproductive Failure (Repeated Pregnancy Loss/Recurrent Implantation Failure/Unexplained I... 1: Introduction to Reproductive Immunology and Reproductive Failure Reference 2: Recurrent Pregnancy Loss and Recurrent Implantation Failure 2.1 Recurrent Pregnancy Loss 2.1.1 Introduction 2.1.2 Definitions 2.1.3 Biochemical Pregnancy and RPL 2.1.4 Diagnostic Criteria for RPL Definition 2.1.5 RPL Attributable to Chance 2.1.6 Types of RPL by Etiology 2.1.7 Types of Unexplained RPL (See Table 2.3) [13] 2.1.8 Incidence 2.2 Recurrent Implantation Failure 2.2.1 Introduction 2.2.2 Definitions 2.2.3 RIF Versus Recurrent IVF Failure References 3: Immune System 3.1 Introduction 3.1.1 Recognition 3.1.2 Response 3.1.2.1 Effector Response (See Fig. 3.1) [1] 3.1.2.2 Memory Response (See Fig. 3.2) [2] 3.2 Types of Immunity 3.2.1 Innate Immunity 3.2.2 Adaptive Immunity 3.3 The Cells of the Immune System 3.4 Lymphocytes 3.4.1 Naïve and Effector Lymphocytes 3.4.2 B Lymphocytes (B Cells) 3.4.3 T Lymphocytes (T Cells) 3.4.4 Natural Killer Cells 3.4.5 NKT Cell 3.5 Mononuclear Phagocytes 3.6 Major Histocompatibility Complex 3.6.1 Introduction 3.6.2 Structure 3.6.3 Function 3.7 Cytokines 3.7.1 Introduction 3.7.2 Functions 3.7.3 Types 3.7.4 Importance References Untitled 4: Immunology of Pregnancy (Reproductive Immunology) 4.1 Introduction 4.2 Fetus as Allograft 4.3 Immune Response in Normal Pregnancy 4.4 Mechanisms of Immunoprotection of Embryo 4.5 Mechanisms of Alloimmune Rejection of Pregnancy References 5: Diagnosis of Alloimmune Factor 5.1 Introduction 5.2 Level One 5.2.1 Test for Genetic Factors 5.2.2 Test for Anatomical Factors 5.2.3 Test for Endocrine Factors 5.2.4 Test for Infections 5.2.5 Test for Autoimmunity 5.2.6 Test for Thrombophilia 5.2.7 Other Tests 5.3 Level Two 5.3.1 Lymphocyte Crossmatch 5.3.2 Peripheral Blood NK Cells (pNK Cells) 5.3.3 Uterine NK Cells 5.3.4 Serum TNF-alpha 5.3.5 HLADQ-alpha Genotype 5.3.6 T-reg Cell Estimation (CD4+CD25+foxP3) 5.3.7 TH1-TH2 Intracellular Cytoplasmic Ratio 5.3.8 KIR Genotyping 5.3.9 CD4/CD8 Ratio References Part II: Lymphocyte Immunization Therapy 6: Introduction to Lymphocyte Immunization Therapy (LIT) 7: History of LIT 7.1 History 7.2 Sir Peter Medawar (1915-1987) 7.3 Dr. Billingham R.E. 7.4 Dr. Taylor C and W. Page Faulk (1981) 7.5 Dr. Alan Beer 7.6 Dr. Mowbray 7.6.1 Conclusions of This Study Were as Follows 7.7 Recurrent Miscarriages Immunotherapy Trialists Group (RMITG) 7.7.1 Aim 7.7.2 Results 7.7.3 Conclusion 7.8 Daya S 7.8.1 Study 7.8.2 Results 7.8.3 Conclusion 7.9 Carp HJA et al. (1997) 7.9.1 Study 7.9.2 Results 7.9.3 Conclusion References 8: Mechanism of Action of LIT 8.1 Introduction 8.2 The Mechanisms of Action of LIT (see Fig. 8.1) [6] References 9: Procedure of LIT 9.1 Introduction 9.2 Indications 9.3 Contraindications 9.4 Criteria for Selection 9.4.1 Group A: Clinical Criteria 9.4.2 Group B: Laboratory Criteria (See Table 9.1) 9.4.2.1 Lymphocyte Crossmatch 9.4.2.2 Assessment of the Peripheral NK Cells 9.4.2.3 Assessment of Endometrial NK Cells 9.4.2.4 Serum TNF-α 9.4.2.5 Assessment of Treg Cells 9.4.2.6 Assessment of Th1:Th2 Cytokine Ratio 9.4.2.7 Conclusion for Investigations 9.5 Prerequisites to LIT 9.6 Procedure References 10: Safety of LIT 10.1 Introduction 10.2 Effects of LIT 10.3 Side Effects 10.3.1 Early Side Effects 10.3.2 Delayed Side Effects 10.4 Effect of LIT on Infants 10.5 Conclusion References 11: Controversies About LIT: REMIS Study 11.1 Controversies About LIT 11.2 REMIS Study 11.3 Observations of REMIS Study (See Fig. 11.1) [1] 11.4 Criticism of REMIS Study 11.5 Significance of REMIS Study References 12: Cochrane Reviews and LIT 12.1 Introduction 12.1.1 Cochrane Database of Systematic Reviews 12.1.2 Objective of Cochrane Reviews 12.2 Cochrane Database of Systematic Reviews for Immunotherapy for Recurrent Miscarriage 12.3 Objective 12.4 Selection Criteria 12.5 Search Strategy 12.6 Cochrane Database Reviews About Immunotherapy in Recurrent Miscarriages 12.7 Results 12.8 Effects of Interventions 12.9 Conclusions 12.10 Quality of the Evidence 12.10.1 Criticism of Cochrane Review 12.10.2 Flaws in Cochrane Reviews (Christiansen O. B.) References 13: Recent Meta-Analyses and LIT 13.1 Introduction 13.2 Need for Newer Meta-Analyses 13.3 New Meta-Analysis of Cochrane Review Data 13.4 New Meta-Analysis of Studies Related to Role of LIT in uRPL (Liu Z et al. 2016) [2] 13.4.1 Conclusion 13.5 New Meta-Analysis of Studies Related to Role of LIT in Recurrent Miscarriages (Cavalcante MB et al., December 2016) [3] 13.5.1 Introduction 13.5.2 Systematic Review of Meta-Analyses 13.5.3 Meta-Analysis of Randomized Clinical Trials 13.5.4 Conclusion 13.6 Recent Meta-Analysis by Cavalcante et al. [4] References 14: Review of International Studies of LIT 14.1 Review of Studies Related to LIT References 15: Case Studies 15.1 Case Study 1: Immunomodulation Using Lymphocyte Immunization Therapy, (LIT), in a Couple Experiencing 15 Repeated Miscarr... 15.1.1 Introduction 15.1.2 Patient Information 15.1.3 Clinical Findings 15.1.4 Diagnostic Assessment 15.1.5 Therapeutic Information 15.1.6 Follow-Up 15.1.7 Outcome 15.1.8 Discussion 15.1.9 Rationale 15.1.10 Primary Takeaway Lessons 15.1.11 Patient Perspective 15.1.12 Informed Consent 15.2 Case Study 2: Role of Immunomodulation with Lymphocyte Immunization Therapy (LIT) in a Couple with Five Unexplained IVF F... 15.2.1 Introduction 15.2.2 Patient Information 15.2.3 Clinical Findings 15.2.4 Diagnostic Assessment 15.2.5 Therapeutic Information 15.2.6 Follow-Up 15.2.7 Outcome 15.2.8 Discussion 15.2.9 Lymphocyte Immunization Therapy 15.2.10 Rationale 15.2.11 Primary Takeaway Lessons 15.2.12 Informed Consent References 16: Future of LIT Reference