The possible role of transplacentally-acquired antibodies to infectious agents, with molecular mimicry to nervous system sialic acid epitopes, as causes of neuromental disorders: prevention and vaccine implications

Clin Dev Immunol. 2006 Jun-Dec;13(2-4):167-83. doi: 10.1080/17402520600801745.

Abstract

Proof of causality of most neuromental disorders (NMD's) is largely unavailable. Lessons from four-decade investigations of the epidemiology, immunology, pathogenesis, prevention and therapy of perinatal infectious agents, which invade directly the nervous system, have led us to propose a new indirect effect hypothesis: maternal transplacentally-acquired antibodies, to agents with epitope molecular mimicry with the developing nervous system, can cross the fetus/infant's blood-nervous system barriers to cause NMD's, clinically manifest years later. Further rationale is provided by relevant evolutionary/developmental (EVO-DEVO) considerations - applicable also to some vaccines. The hypothesis is being tested in: (a) older pregnancy studies with available maternal and newborn sera, and follow-up of the progeny for NMD's; and (b) NMD registry individuals linked to their stored newborn blood spots. Preliminary results support a possible role for schizophrenia of high-tittered antibodies to some agents (toxoplasma, influenza and herpes simplex type 2 virus). A model that includes likely genetic and postnatal influences is schematized and a list of putative agents and factors, based on varying rationales, is tabulated. In case pilot studies are confirmed, the identified agent(s) and antibodies would need to be tested in new prospectively enrolled pregnant women, so as to establish further risk factors leading to possible preventive modalities.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Bacterial / analysis
  • Antibodies, Viral / analysis
  • Central Nervous System Diseases / diagnosis
  • Central Nervous System Diseases / etiology
  • Central Nervous System Diseases / therapy*
  • Epitopes / immunology
  • Female
  • Fetus / immunology
  • Humans
  • Immunization* / adverse effects
  • Maternal-Fetal Exchange*
  • Molecular Mimicry
  • N-Acetylneuraminic Acid / immunology*
  • N-Acetylneuraminic Acid / metabolism
  • Pregnancy / immunology*
  • Pregnancy Complications, Infectious / immunology
  • Pregnancy Complications, Infectious / prevention & control
  • Vaccines / administration & dosage
  • Vaccines / immunology

Substances

  • Antibodies, Bacterial
  • Antibodies, Viral
  • Epitopes
  • Vaccines
  • N-Acetylneuraminic Acid