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

Infertility-associated Sperm Antigens

Antisperm antibodies are composed of numerous antibodies interacting with multiple sperm components. The number of identified sperm antigens has increased since the 1990s. Shetty et al. reported on their results achieved using a 2D-electrophoresis technique:[9] 98 sperm auto- and isoantigenic protein spots were recognized by sera with ASA from infertile males and females but not from fertile subjects. Dozens of sperm-specific antigens were reportedly associated with infertility, including lactate dehydrogenase-C4 (LDH-C4),[10] fertilization antigen (FA)-1,[11,12] SP22,[13,14] GP20,[15] SP-10,[16] YWK-II antigen,[1] rSMP-B,[17] BS63,[18] HSAP,[19] YLP(12),[20] PH-20,[21] Sptrx,[22,23,24,25,26] proteasomal subunits,[27,28] nuclear autoantigenic sperm protein (NASP), BS17[1] and HED-20 (zyxin) ( Table 1 ).[1] Each antigen is a distinct and separate entity and is produced by different cells in the reproductive tract, such as germ cells, epididymal epithelial cells and Sertoli cells.[29] Many of their genes have been cloned and their recombinant proteins have also been acquired. However, the exact identification of the biochemical nature of the cognate antigens of ASAs is possible only after reliable separation of the sperm membrane proteins and confirmation of their potency to bind ASAs. Sperm membrane proteins could undergo changes in the antigenic characteristics during sperm maturation and capacitation, possibly by increasing accessibility of some sialic acid residues and of the core peptide, particularly the GPI anchor.[30,31] In fact, it was difficult to separate a single predominant target antigen identified to interact with all the ASAs yet.

In addition to those sperm-specific antigens listed in Table 1 , many other antigens were reportedly related to activation of zona pellucida (ZP) binding, such as trypsin, proacrosin, acrosin and rabbit sperm autoantigen I; involved in acrosome reaction (AR; e.g., M42); participants in sperm-egg membrane fusion (e.g., PH-30 and M29); or involved in ZP penetration, such as MS 207.

Some new specific epitopes of sperm antigens were found recently by using phage-display technology instead of the recombinant antigens being researched. These new epitopes have higher specificity than recombinant antigens, and lower cross-reactivity with other shared antigens. Naz et al.[32] used this technology to delineate the peptide sequences that are involved in human immunoinfertility, and the peptide sequences present on human sperm cells that are involved in binding to human ZP. They used the antibody-positive sera from immunoinfertile men to screen seven clones that had dodecamer sequences in a random order, designated #2, PSALGRFTRGPL; #22, SLIFVTISSEWG; #69, LSLSLDLLTFRT; #77, PDIRHYFIQNRG; #81, GCRIVYRRPLHL; #84, RTAGFDIKLIDT; and #95, RIQYQAISTVSL. All seven peptides reacted strongly with the sera from infertile males, but not with the sera from fertile men. Due to the difficulty in identifying ASAs, our group screened phage libraries using specific ASAs from rabbits immunized with human sperm. Four dodecamer sequences closely associated with fertility were obtained. These specific epitopes have been found to be superior to other known sperm-specific antigens in the diagnosis of ASA (Lu J-C et al., Unpublished Data) .

In general, mulitple antigens react with ASAs. These sperm antigens, which are involved in fertilization are still poorly understood. ASAs can only inhibit a single sperm epitope and function. No single sperm antigen has yet been found that can completely block the effect of ASAs.

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