Anti-phospholipid antibodies and other immunological causes of recurrent foetal loss--a review of literature of various therapeutic protocols.
OBJECTIVE
An immune-based aetiology is one of the several accepted causes for recurrent foetal loss (RFL). However, most of the immunological theories have not fulfilled the criteria for causality. This is a review of the various immunological causes of RFL and the outcome of different treatment protocols.


METHODS
Both auto- and alloimmune maternal immunological abnormalities have been proposed to account for foetal loss. Among the autoimmune factors, anti-phospholipid antibodies (APAs) have been demonstrated to be the strongest risk factors for foetal loss, the prevalence of which is as high as 40% in women with RFL. Other autoimmune antibodies implicated in RFL are anti-nuclear antibodies (ANAs), anti-thyroid antibodies and anti-endothelial cell antibodies. The alloimmune factors implicated in pregnancy loss of unknown aetiology include abnormal natural killer (NK) cell activity, alteration in T helper 1 (Th1) and T helper 2 (Th2) ratios, presence of alloimmune antibodies like anti-paternal cytotoxic antibodies, anti-idiotypic antibodies, mixed lymphocyte reaction blocking antibodies and abnormal expression of HLA-G molecules. Management of patients with RFL is mainly based on immunomodulatory (prednisolone, intravenous immunoglobulins, plasma exchange, paternal lymphocyte therapy), anti-aggregation (aspirin) or anti-coagulation (unfractionated or low molecular weight heparin) agents.


RESULTS
Low-molecular-weight heparin with low-dose aspirin has been found to be the most effective treatment for women with APAs and RFL. Differences in dosage, timing of treatment, inclusion criteria, outcome assessment parameters etc. are some of the factors which have resulted in discrepancies in various reports.


CONCLUSIONS
Identification of the immunological mechanisms involved in pregnancy loss and the action of different therapeutic reagents is important so that effective therapies can be designed and investigated.
Shetty
Shrimati
S
National Institute of Immunohaematology (ICMR), KEM Hospital, Parel, Mumbai 400012, India.
Ghosh
Kanjaksha
K
D000022:Abortion, Spontaneous / Q000188:drug therapy / Q000209:etiology / Q000276:immunology*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D017152:Antibodies, Antiphospholipid / Q000276:immunology* / Q000378:metabolism; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D006680:HLA Antigens / Q000276:immunology / Q000378:metabolism; D059951:HLA-G Antigens; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000627:therapeutic use; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000188:drug therapy / Q000209:etiology / Q000276:immunology*; D011374:Progesterone / Q000627:therapeutic use; D011372:Progestins / Q000627:therapeutic use; D012008:Recurrence; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D017152:Antibodies, Antiphospholipid; D005343:Fibrinolytic Agents; D006680:HLA Antigens; D059951:HLA-G Antigens; D006495:Heparin, Low-Molecular-Weight; D015395:Histocompatibility Antigens Class I; D016756:Immunoglobulins, Intravenous; D011372:Progestins; D011374:Progesterone; D011239:Prednisolone; D001241:Aspirin