Alina Domagala

Identification of sperm immunoreactive antigens for immunocontraceptive purposes: a review.

Antisperm antibodies (ASA) may be a reason of infertility in some individuals. They may affect pre- as well as post-fertilization stages of the reproductive process. There is ongoing progress in the identification of sperm antigens related to fertilization. The employed methods for this purpose include recombinant DNA technology and the most advanced proteomic analysis. This paper enlists the different approaches undertaken in order to identify and characterize the immunoreactive sperm antigens. We have mainly focused on those, which have been already studied in regard of their immunocontraceptive potential, although it has been impossible to include all published data concerning the topic in a single article. Few novel sperm auto- and isoantigens, discovered recently, have also been reviewed even if their role in fertilization has not been yet established.

Antisperm antibodies in prepubertal boys with cryptorchidism.

The presence of antisperm antibodies in male individuals before puberty is controversial due to the lack of finally differentiated male germ cells. It was questioned whether the pathologic conditions of the male gonad may influence antisperm antibody formation in individuals before puberty. Sera samples of 76 individuals and 10 healthy boys with testicular failure (mainly uni- or bilateral cryptorchidism) were examined by means of indirect immunobead-binding test (IDIBT). The presence of antisperm antibodies was found in 3.95% of the studied subjects. Antibodies recognizing antigenic determinants present on the surface of mature sperm cells may be produced before puberty in individuals suffering from cryptorchidism or the other gonadal disorders. Antisperm antibodies that did develop in a minority of the studied male population may be proof for individual predispositions to autoimmune reactions.

Immunoprecipitation of sperm and somatic antigens with antibodies from sera of sperm-sensitized and anti-sperm antibody-free individuals

Problem:  Immune infertility may result from the presence of anti‐sperm antibodies (ASA) in sera of sensitized individuals or in their genito‐urinary millieu. According to some authors, sera of pre‐pubertal boys with genital disorders may contain ASA, too. When identified and characterized, sperm antigenic components can be employed for diagnostic and/or for immunocontraceptive purposes.

An isoimmune response to human sperm clathrin in an infertile woman with systemic lupus erythematosus.

We have employed a proteomic approach to study the immune response to human sperm in an infertile female patient suffering from systemic lupus erythematosus (SLE). Human sperm antigenic extracts were resolved by means of two-dimensional electrophoresis and electroblotted onto nitrocellulose membranes. The membranes were incubated with serum from the SLE patient. Sperm antigens that were reactive to polyclonal antibodies were next visualized on X-ray film, using the enhanced chemiluminescence (ECL). Three spots corresponding to the positions of sperm immunoreactive antigens on a nitrocellulose membrane were localized in a silver stained gel and subjected to mass spectrometry. A database search of the sequences recognized by the analyzed SLE serum revealed its homology to the clathrin heavy chain (CHC). Further analysis revealed that anti-CHC antibody reacted with multiple sperm antigenic determinants, resolved by either one- or two-dimensional electrophoresis. When studied by immunofluorescence, we demonstrated anti-CHC antibody reactivity with the sperm tail tip (corresponding to the sperm agglutination pattern), also with the principal piece and with cytoplasmic droplets around the sperm midpiece. Live sperm clearly exhibited reactivity with the midpiece. This study demonstrates clathrin heavy chain on human sperm using serum of an infertile individual with a concomitant autoimmune disease.

Modification of humoral antisperm response

Considerable effort has been made to create animal models in which functions of the human immune system can be studied under the experimentalin vivoconditions. An important step in this direction was demonstrated when the SCID mice were stably grafted with human lymphoid cells. This animal model allows the testing of various antigens and adjuvants inin situconditions inducing human immune effector cells and permitting the optimization of the subsequent response.