Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004364 (autoimmune disease)
 24,845 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Sperm-specific antigens behave immunologically more like foreign than self antigens. 2. Consequences of autoimmune response to testicular and/or sperm antigens can result in allergic orchitis, postvasoligation orchitis, and infertility. In these conditions, multiple pathogenetic mechanisms, including immune complexes and T-cell-mediated immune reaction, have been shown to be important. 3. Normally, factors that circumvent sperm autoimmune disease are likely to be multiple. Besides the mechanism of sperm-antigen sequestration, other controlling mechanisms also should be considered.
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PMID:Autoimmunity to sperm. 68 9

The results of both clinical and experimental studies suggest that immunologic mechanisms may be significant in the pathogenesis of idiopathic infertility. We have defined and preliminarily characterized a number of immunoregulatory genes which control the phenotypic expression of infertility associated with autoimmune disease of the testis. Our studies utilizing the murine model of experimental allergic orchitis have clearly demonstrated that both classical (class II antigens) and nonclassical major histocompatibility complex-linked immune response genes play a central role in controlling disease susceptibility. We have mapped one nonclassical immune response gene, orchitis susceptibility gene-1 (Orch-1), to an interval of ca. 100 kilobases within the H-2S-H-2D region. In addition, immunogenetic analyses have identified two immune suppression genes, Orch-2 and Orch-3, which control active immunoregulatory mechanisms governing the phenotypic expression of disease resistance. The genetic control of autoimmune infertility in this model therefore appears to be polygenic.
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PMID:The immunogenetics of susceptibility and resistance to murine experimental allergic orchitis. 129 Jul 48

The authors report a nulliparous patient presenting with infertility and hyperprolactinemia. She underwent transsphenoidal surgery after radiological investigation disclosed an enlarged pituitary gland which did not respond to bromocriptine therapy. The removed tissue had histological features consistent with adenohypophysitis including a diffuse lymphocytic infiltrate. The lymphocyte subsets present in the infiltrate were characterized by immunohistochemical methods to establish the contribution of different elements of the cellular immune response. Lymphocytes bearing CD4 antigen (helper-inducer cells) were most prominent and appeared to bear the majority of the interleukin-2 receptor (expressed during lymphocytic activation) present in the pituitary gland. A few B lymphocytes were also observed. The location of the major histocompatibility antigen (classes I and II) and interleukin-2 receptor correlated with the lymphocytes and macrophages rather than with the stromal or parenchymal elements of the pituitary. Lymphocytic adenohypophysitis is an unusual cause of pituitary enlargement which can mimic a pituitary tumor, and is sometimes associated with hyperprolactinemia. In women of child-bearing age, it almost always occurs during pregnancy or the postpartum stage. The autoimmune disorder reported here has not previously been associated with infertility nor has the lymphocytic infiltrate of the pituitary previously been analyzed in detail by modern immunological methods.
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PMID:Lymphocytic adenohypophysitis presenting as infertility. Case report. 201 81

This article has reviewed the immunologic factors of human infertility and some of the animal models that have provided experimental evidence for the better understanding of these disorders. It is clear that definitive evidence for human autoimmune diseases of the gonads is still lacking. However, recent findings in infertile men represent tangible support for this possibility and should stimulate further studies. Insofar as these diseases are relatively rare, meaningful clinical investigations can best come from a multicenter effort based on patients with well-defined clinical and laboratory profiles. To arrive at a firmer immunologic basis for these human diseases, it will be helpful to extrapolate from experimental studies. For both testicular and ovarian diseases, it will be desirable to refine the methods for quantifying humoral and cellular immune responses to the organ-specific autoantigens in the testis and ovary. Immunohistochemical localization of immune reactants is likely to be successful when performed early in the disease process and on tissue from patients with active disease. The nature of the immune deposits in testes will need to be confirmed by the classic approach of elution of antibody from the tissue with dissociating agents, followed by quantitation. The large quantity of tissue required for study can come from orchiectomy specimens from infertile men with unilateral vasal stenosis. In addition to immunologic reactions that lead to inflammation, future studies should take into consideration the possible existence of autoantibodies that react against hormone receptors or other functional ligands involved in ovarian or testicular physiology. Despite the paucity of evidence for human autoimmune diseases of the gonads, the likelihood of existence of these diseases is also supported by the ease with which experimental autoimmune disease of the gonads can be induced. We have described the experimental models of gonadal autoimmune diseases in detail, since analysis of these diseases has led to some unique contributions to immunopathology research and the physiology of the gonads. It is anticipated that future studies will characterize the target antigens as well as the local and systemic mechanisms that prevent autoimmune disease of the gonads in normal individuals. Moreover, it is anticipated that the model of neonatal thymectomy and oophoritis/orchitis will help to define the intricate interplay among thymic function, tolerance mechanisms, and autoimmunity. It is important to emphasize that research on the maternal-fetal immunologic relationship is a rapidly moving and controversial field. Although we have tried to point out controversial areas, the reader may wish to consult several excellent recent reviews. The anatomy and function of the hemochorial placenta and decidua are extraordinarily complex.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Immunologic basis of reproductive failure. 206 21

Antisperm antibodies have been implicated as a causative factor of infertility and pregnancy wastage. Since concomitant autoimmune phenomena were reported in men with antisperm antibodies, we investigated known antisperm antibody-positive sera from 25 women, 27 men, and the respective seminal plasma samples. The investigated autoimmune panel included a search for antinuclear antibodies, autoantibodies (in IgG, IgM and IgA isotypes) to seven phospholipids (cardiolipin, phosphatidylserine, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidic acid), to four histone subfractions (H1, H2A, H3, H4), and to four polynucleotides [ssDNA, dsDNA, poly(I), and poly(dT)], total immunoglobulin levels, and sperm antibody titers. The sera were also evaluated for the presence of a common anti-deoxyribonucleic acid antibody, and anticardiolipin antibody idiotypes. Levels of sperm antibody titers were significantly lower in women than in men. Both men and women with antisperm antibodies demonstrated elevated total IgG levels compared with those of normal control subjects. Only women showed elevated levels of total IgM. Sera from 24% of women and 11% of men with antisperm antibodies demonstrated antinuclear antibody titers greater than 1:40. The most striking autoantibody abnormalities were found among antiphospholipid antibodies. Sera from women with antisperm antibodies demonstrated higher autoantibody production than was found in their male counterparts. A significant correlation was found between antisperm antibodies and IgM anticardiolipin and IgA anti-phosphatidylinositol in women and between sperm antibodies and IgA phosphatidylserine antibodies in men. The presence of anticardiolipin and anti-deoxyribonucleic acid antibody idiotypes was significantly more frequent in women than in men. By means of discriminant analysis and variables selected by this mathematical model, the identification of 24 of 25 women and 26 of 27 men with antisperm antibodies was correctly predicted. These results suggest that women and men respond differently to sperm antigens. The apparent cross-reactivity between sperm antibodies and other autoantibodies, usually associated with autoimmune disease, suggests that a polyclonal B cell activation, similar to that seen in autoimmune diseases, occurs in patients with sperm antibodies.
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PMID:Autoantibodies and common idiotypes in men and women with sperm antibodies. 334 22

There are several antigens of the human sperm cell that can stimulate production of autoantibodies in certain individuals. This occurs in a number of spontaneous cases and leads to a condition of immunological infertility. It also occurs in a majority of men who have had a vasectomy. There are currently many new developments for the detection of the antibody, the study of its significance, and in the treatment of this autoimmune disease. As for the diagnostic testing of the serum, there are the classical methods of agglutination, namely, GAT, TSAT, TAT, and CTAT, and of immobilization. There are also the newer methods of the passive hemagglutination assay, the radio-label-antiglobulin test, the ELISA, the hemadsorption procedure, and the ATP-luminescence cytotoxicity method, plus indirect MAR (mixed antiglobulin reaction) and IBT (immunobead test) procedures. For testing of the genital secretions, sperm cells can be evaluated directly by the MAR and IBT methods, and cervical mucus, after being dissolved, can be tested by the MIS (microscale method) or an indirect IBT procedure. Interpretations of the significance of sperm antibody have been passed on epidemiologic values and also on direct fertilization-inhibition studies. Treatment of the antibody problem has been based on several approaches, but the most promising approach has been the use of intermittent high-dose steroid medication. A number of studies have shown good results by this procedure of immunosuppression.
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PMID:Sperm antigens and autoantibodies: effects on fertility. 371 76

19 wives of 236 couples had positive sperm agglutination tests. (SPAT) 6 of the 19 belonged to the 70 couples (9.4%) with no no known cause for infertility; 11 belonged to the group of 154 couples (7.1%) with a known cause; and 2 to the 12 couples inadequately investigated (15.7%). 6 of these 19 women (31.6%) became pregnant without condon therapy; of these 6, 3 had no known cause for infertility and 3 had a known cause. 11 husbands had positive sperm aggluatination tests. 4 of these 11 were among the 70 couples (5.6%) with no known cause for infertility, while the other 7 were among the 154 couples (4.5%) with a known cause. 5 of their wives (45.5%) became pregnant without any treatment. Outcomes of 8 of 11 pregnancies were normal deliveries and no abortioons, which showed that positive SPAT had no apparent effect on the pregnancies. There was no relationship between postitive SPAT and history of venereal disease, allergy, autoimmune disease, abortioon, postcoital tests, or ABO imcompatability.
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PMID:Sperm-agglutinating antibodies in 236 infertile couples. 503 96

Breeding for fine black fur has generated a colony of mink wherein 20-30% of the males are infertile. Two clinical groups are distinguishable: one being infertile from the start (primary infertility), and the other infertile after one or more years of fertility (secondary fertility). Although the etiology of primary infertility is unknown, the available data indicate that secondary infertility is associated with an autoimmune disease of the testis. Thus, male mink with secondary infertility have (a) higher prevalence and levels of anti-sperm antibody when compared with animals with primary infertility, and the antibody prevalence varies with fur color; (b) severe monocytic orchitis (47%) and/or aspermatogenesis (75%) with negative cultures for bacterial, fungal, mumps, or Coxsackie B viral organisms; (c) massive and extensive granular deposits of mink IgG and/or C3 (71%), typical of immune complexes, along the basal lamina of seminiferous tubules; (d) testes that when eluted with buffer or low pH yielded IgG that was 10-fold enriched in anti-sperm antibody activity as compared with serum IgG; and (e) no immunopathologic evidence of Aleutian mink disease. Although the sperm antigen-antibody complexes in the testis may be important as a pathogenetic mechanism of the testicular disease, there is no correlation between fluorescent anti-sperm antibody detection in the serum and the infertile state. The infertile black mink is a new model of infertility associated with naturally occurring autoimmune disease of the testis.
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PMID:The black mink (Mustela vison). A natural model of immunologic male infertility. 611 40

Lymphocytic adenohypophysitis (LAH) is an autoimmune disorder of the pituitary gland with a predilection for the peripartum period and often mimics a pituitary adenoma. We sought to define the clinical, endocrinologic and radiographic characteristics differentiating peripartum LAH from pituitary adenoma to enable the use of noninvasive diagnosis and appropriate therapy. From published reports and our own case, the clinical histories and laboratory and radiographic studies of 45 patients fulfilling the diagnosis of peripartum LAH were reviewed. History of infertility or menstrual irregularity, symptomatology, endocrinologic evaluation, diagnostic imaging and associated medical conditions were analyzed. For comparison, 806 patients with pituitary adenoma and pregnancy from published series were evaluated. The spontaneous pregnancy rate in pituitary adenoma patients was 2.4% vs. 100% in LAH patients. Visual disturbances and headaches were significantly more frequent in patients with LAH. Prolactin levels were significantly lower in patients with LAH than in those with pituitary adenomas (34.6 +/- 46.3 [SD] vs. 393.0 +/- 300.4, P < .0001). Abnormalities in thyroid and/or adrenal function were also more common in patients with LAH (57.5% vs. 2.5%, P < .001). There were no distinguishing characteristics on radiographic studies. History and endocrinologic evaluation can differentiate between LAH and pituitary adenoma in the peripartum patient.
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PMID:Differentiating lymphocytic adenohypophysitis from pituitary adenoma in the peripartum patient. 762 53

Zona pellucida 3 (ZP3) is a major glycoprotein of the zona pellucida that possesses the sperm receptor function. ZP3 induces autoantibody that can block sperm/oocyte interaction. However, the feasibility of a ZP3 contraceptive vaccine has been marred by the finding that ZP3-specific T cells mediate ovarian autoimmune disease. Moreover, as reported in this work, only some inbred mouse strains respond to the ZP3 peptide. We now describe a chimeric peptide that induces Abs to native ZP3 regardless of the MHC haplotype of the inbred mice tested. Study in one mouse strain resulted in reduction in fertility that correlates well with zona pellucida Ab titer, and most importantly, the mice do not develop concomitant autoimmune oophoritis. Moreover, the infertility was completely reversible. The design of the vaccine chimeric peptide is governed by the inclusion of two essential components: 1) a promiscuous foreign T cell peptide capable of eliciting a Th cell response regardless of the MHC haplotype of the animals, and 2) the native B cell peptide of ZP3 that has been modified by substitution of residue(s) critical for T cell but not B cell response to ZP3.
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PMID:A zona pellucida 3 peptide vaccine induces antibodies and reversible infertility without ovarian pathology. 765 Mar 99


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