Antisperm Immunity and Infertility

Jin-Chun Lu; Yu-Feng Huang; Nian-Qing Lu

Disclosures

Expert Rev Clin Immunol. 2008;4(1):113-126. 

In This Article

Antisperm Antibody

An ASA is defined as an immunoglobulin with antibody activity against a sperm antigen that plays a role in fertility, since not every antibody that binds to the sperm surface influences sperm function.[4] However, methods currently used to detect ASAs in serum, seminal plasma or cervical mucus and on sperm only measure those immunoglobulins that bind to sperm components. Whether these immunoglobulins had antibody activity remains uncertain.

The production of ASAs is closely related to the stimulation of sperm antigen. However, numerous antigens on the sperm surface are shared with somatic cells. Evidence is presented for common antigens or cross-reactive antigens on human sperm and T lymphocytes.[5] ASA titers in sera, sperm extracts and the seminal plasma of the infertile subjects were reduced significantly after absorption with sperm, thymocytes or the T-cell line CCRF-CEM. Moreover, lymphocytes from the infertile patients, when stimulated with pokeweed mitogen in vitro, produced antisperm and anti-T-lymphocyte antibodies at significantly higher titers than normal controls.

Similarly, the cross-reactivity of ASAs with other autoantibodies, including antithymocyte antibody, antinuclear antibody, antiphospholipid antibody, was also confirmed.[6] The apparent cross-reactivity between ASAs and other autoantibodies suggests that a polyclonal B-cell activation,[6] similar to that seen in autoimmune diseases, occurs in patients with ASAs. In addition, the immunoglobulin heavy chain cDNA sequences of ASAs showed extremely high homology with previously reported immunoglobulin germline DNA sequences, also implying that ASA might be natural autoantibodies.[7]

Therefore, a question arose, which of the sperm antigens could detect ASA. If we want to detect ASAs that cause infertility, we must get standard sperm antigens closely associated with fertilization. An ideal sperm antigen should be sperm specific, accessible to the antibody and play a key role in fertilization.[8] In addition, the sperm antigen, alone or after conjugation with an appropriate carrier protein, should be able to raise a high titer and a long-lasting antibody response both in circulation and locally in the genital tract. ASAs in men should be induced by epitopes that are specific to sperm and located on the sperm surface; but how do we get such sperm antigens? There are not any definite answers at present.

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