The Immunopathogenesis of Antisperm Antibodies in Men: Role of Trauma, Infection, Surgery and Breakdown of Immune Privilege

Abstract

Antisperm antibodies (ASA) are immunoglobulins against sperm surface or intracellular antigens and are a significant but poorly understood component of immunological male infertility. Under normal physiological conditions developing germ cells are protected from improper immune identification by a combination of structural, cellular and molecular mechanisms collectively called testicular immune privilege. The blood-testis barrier, Sertoli-cell immunoregulatory activity, local anti-inflammatory mediators and systemic immunological tolerance suppress immune responses to sperm-specific antigens. However, trauma, infection, surgery, obstruction of the reproductive system, and other pathologic events may interfere with these protective mechanisms. Exposure of antigen-presenting cells to normal sequestered sperm antigens can stimulate activation of T lymphocytes, B-cell differentiation and generation of sperm-reactive IgG and IgA antibodies. In addition, inflammation can affect the blood–testis and blood–epididymis barriers through cytokine signalling, oxidative stress and tissue damage, which may enhance antigen exposure and immune activation. The vasectomy is one of the better described surgical triggers, as stoppage of sperm transport may cause extravasation of sperm, granuloma formation and increased antigen exposure. Local immunological homeostasis can be disrupted in a similar fashion by genital infections (e.g., epididymo-orchitis) and other inflammatory disorders. Testicular trauma and torsion can cause direct testicular injury and release of germ-cell antigens. Clinical implications of ASA depend on antibody class, antigen specificity, titre, sperm binding site and extent of sperm coating. Functionally relevant antibodies can cause sperm agglutination, poor motility, altered cervical mucus penetration, aberrant capacitation, interference with the acrosome reaction and impaired sperm oocyte contact. However, the clinical relevance of ASA is still inconsistent and major guidelines do not suggest frequent testing for ASA in the first work-up of male infertility. The overview of the immunopathogenesis of ASA emphasises trauma, infection, surgery and disruption of male reproductive immune privilege and points out diagnostic limits and topics for additional investigation.