Validity and cost-effectiveness of antisperm antibody testing before in vitro fertilization

OBJECTIVE: To determine the usefulness of and cost-effectiveness of antisperm antibody testing in the prediction of poor fertilization rates in couples undergoing IVF. DESIGN: Retrospective cohort study. SETTING: A hospital-based reproductive endocrinology and infertility practice. PATIENT(S): Male partners of 251 couples undergoing IVF between 1992 and 1997. MAIN OUTCOME MEASURE(S): Fertilization rates in couples undergoing conventional IVF. RESULT(S): One hundred nineteen couples were evaluated for antisperm antibodies; fertilization rates were similar in those couples whose husbands were and were not tested (64% versus 68%). Antisperm antibodies were detected in 16 men. Four (25%) of the 16 couples whose husbands had antisperm antibodies fertilized < or = 50% of oocytes, compared with 31 (30%) of the 103 couples whose husbands did not have these antibodies. Overall, 21 couples (8.4%) experienced complete fertilization failure. In a program that included antisperm antibody testing for selected couples and intracytoplasmic sperm injection (ICSI) for those who tested positive, it would cost $11,735 to prevent a fertilization failure (assuming ICSI were 100% effective), whereas it would cost $9,250 to perform ICSI in a second IVF cycle for those who initially failed. CONCLUSION(S): In this practice setting, antisperm antibody testing has low sensitivity in predicting low or no fertilization and does not appear to be cost-effective when selectively ordered as part of an IVF workup.     

The effect of the antisperm auto-antibody-bound sperm on in vitro fertilization outcome

To evaluate the effects of antisperm auto-antibody-bound sperm on the outcome of in vitro fertilization-embryo transfer (IVF-ET), 160 infertile couples undergoing treatment by in vitro fertilization were recruited in this study. In the study group (11 couples, 15 cycles), the male partners were positive for antisperm autoantibodies determined by immunobead test (IBT). In the control group (149 couples, 152 cycles), the men had no such antibodies. The percentages of fertilization rate, cleavage rate and pregnancy rate of the study group and control group wer 75.0 +/- 5.2% vs. 69.3 +/- 2.4%; 82.8% +/- 3.7% and 6.7% +/- 11.8%, respectively. There were no significant differences in in vitro region, type and/or percentage of sperm-bound antibodies also had no effect on the in vitro fertilization outcome. In conclusion, in vitro fertilization-embryo transfer is not significantly affected by antisperm autoantibody-bound sperm determined by immunobead test.     

An experimental study on inhibitory effect of Chinese medicine tai-bao on antisperm antibody

OBJECTIVE: To investigate whether Chinese medicine Tai-bao could inhibit antisperm antibody in experimental mice. METHODS: The experimental immunoinfertility mice were due to antisperm antibody induced by injection of human sperm membrane antigens. The experimental immuno-infertile mice used in the present study were divided into four groups including Tai-bao high dose group (46.8 g.kg-1.d-1), Tai-bao low dose group (31.2 g.kg-1.d-1), prednisone group and normal saline group. The enzyme linked immune sorbent assay (ELISA) and microcytotoxic assay were used for detection of antisperm antibody. The change of levels of antisperm antibody before and after treatment, pregnant rate, and the number of implantation were investigated in tested mice. RESULTS: The pregnant rates in normal saline group, prednisone group, Tai-bao high dose group and low dose were 38.89%, 47.06%, 70.00% and 75.00% respectively. The rate of pregnancy in Tai-bao low dose group was significantly higher as compared with normal saline group (P < 0.05). The rate of implantation in Tai-bao low dose group was significantly higher than that in prednisone group (P < 0.05). The results of detection of the cytotoxic antibody to sperm showed that cytotoxic percentages in Tai-bao high dose group (63.0 +/- 10.3%) and prednisone group (56.3 +/- 13.7%) were significantly lower (P < 0.05 and P < 0.01) than that in normal saline group (72.84 +/- 5.05%). CONCLUSION: Chinese medicine Tai-bao possesses regulatory effect on reproductive immune function, inhibitory effect on antisperm cytotoxic antibody, and promoting effect on pregnancy.     

Heterogeneous antibody responses in tuberculosis

Antibody responses during tuberculosis were analyzed by an enzyme-linked immunosorbent assay with a panel of 10 protein antigens of Mycobacterium tuberculosis. It was shown that serum immunoglobulin G antibodies were produced against a variety of M. tuberculosis antigens and that the vast majority of sera from tuberculosis patients contained antibodies against one or more M. tuberculosis antigens. The number and the species of serologically reactive antigens varied greatly from individual to individual. In a given serum, the level of specific antibodies also varied with the antigen irrespective of the total number of antigens recognized by that particular serum. These findings indicate that person-to-person heterogeneity of antigen recognition, rather than recognition of particular antigens, is a key attribute of the antibody response in tuberculosis.     

Regulation by the H-2 gene complex of macrophage-lymphoid cell interactions in secondary antibody responses in vitro

The ability of antigen-bearing syngeneic and allogeneic peptone-induced peritoneal exudate macrophages to support development of primary and secondary antibody responses by murine lymphoid or spleen cells in vitro has been investigated. The antigen used was the terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT). Syngeneic and allogeneic macrophages supported development of comparable primary antibody responses to GAT, indicating that genetic restrictions do not limit efficient macrophage-lymphocyte interactions in primary responses. By contrast, immunized spleen or lymphoid cells developed secondary antibody responses preferentially when stimulated in vitro with GAT on macrophages syngeneic to the macrophages used to present GAT during in vivo immunization. Thus, genetic restrictions regulate efficient macrophage-lymphocyte interactions in secondary antibody responses. These restrictions have been demonstrated from 2 to 8 wk after a single immunization with limiting quantities of GAT and are controlled by the H-2 gene complex. The implications that immune lymphocytes selectively recognize and respond to antigen presented in the context of the macrophage membrane-antigen complex which sensitized the lymphocytes initially are considered.     

Induction of nephrotoxic nephritis with purified antibody: preparation, properties and assay of antibody

The effects of Vinca alkaloids on the vas deferens have been examined after in vitro and in vivo administration. In the organ bath, vinblastine (1 X 10-4M for 4 hr) caused an increase in sensitivity to noradrenaline and biochemical, histochemical and ulstrastructural signs of noradrenaline depletion from the nerves supplying the outer longitudinal muscle layer. After intravenous injection of Vinca alkaloids the nerve fibres seemed less affected. It is concluded that the apparent resistance to the drugs in vivo is largely due to low tissue perfusion.     

Induction of IgE antibody production in mice with different DPT-vaccine preparations

A historical cohort study was performed to assess cardiovascular morbidity and mortality in Type 2 (non-insulin-dependent) diabetic patients. The data were collected from 1967 to 1989 in four Dutch general practices performing the Continuous Morbidity Registration Nijmegen. Each newly diagnosed Type 2 diabetic patient fulfilling the WHO criteria (n = 265) was matched to a control patient for practice, sex, age, and social class. Inclusion started in 1967, the first year of the still ongoing, Continuous Morbidity Registration Nijmegen. On average, a follow-up of 6.8 years (range 1 month-22 years) was realized. Compared to the non-diabetic control patients, the Type 2 diabetic patients showed higher cardiovascular morbidity (risk ratio 1.76, 95% CI 1.34-2.30) and a higher mortality rate (risk ratio 1.54, 95% CI 1.07-2.23). Mortality after 10 years was 36% vs 20% (p < 0.01), the median survival time 16 years vs 19 years. The cumulative survival rates were significantly different (p < 0.01) between patients and controls in the age group 65-74 years. The higher mortality in Type 2 diabetic patients was completely due to an excess of cardiovascular death (risk ratio 2.05, 95% CI 1.24-3.37).     

Behavioral and psychological responses to HIV antibody testing.

The development of tests to identify the antibody to human immunodeficiency virus (HIV) has made it possible to diagnose infection with the virus prior to the development of physical symptoms. The introduction of these tests raises questions regarding the effects of informing individuals that they have been infected with a fatal virus and the usefulness of antibody testing in promoting behaviors that would reduce the spread of acquired immunodeficiency syndrome (AIDS). Research that has examined changes in psychological distress and in behaviors associated with HIV infection among individuals who have undergone antibody testing is reviewed. Methodological issues encountered in studying behavioral and psychological responses to antibody testing are identified, and directions for future research are offered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Specific immunosuppression of human anti-murine antibody responses in hu-PBL-SCID mice

Severe combined immunodeficient (SCID) mice were reconstituted with normal human peripheral blood leukocytes (PBLs) and were shown to produce a human anti-mouse immunoglobulin antibody response on immunization with heat-treated murine monoclonal IgG1 antibody to ovalbumin, referred to as ha-Mab-2. The human anti-mouse antibody response was proportional tot the number of B cells and mononuclear cells transferred from a given batch of PBL. However, pretreatment of hu-PBL-SCID mice with a tolerogenic covalent conjugate of monomethoxypolyethylene glycol (mPEG) and Mab-2 suppressed this response on subsequent injections of ha-Mab-2, and this suppression was shown to be antigen-specific, i.e., it did not suppress the antibody response to ovalbumin and did not affect the level of production of human immunoglobulin of hu-PBL-SCID mice. The suppression was due to the generation of human suppressor CD8+ T (Ts) cells, which down regulated CD4+ helper T cells in an antigen and HLA class I specific manner, i.e., these findings were in accord with the previously shown immunosuppressive effect of tolerogenic mPEG conjugates in normal mice.     

Survey of the diagnosis and management of antisperm antibodies

A questionnaire was sent to all Human Fertilization and Embryology Authority-registered reproductive medicine centres throughout the UK to survey their policy for the diagnosis and management of antisperm antibodies. Forty-eight responses were received from the 74 units that use husbands' spermatozoa for treatments (65%). Most centres use at least one test to detect antibodies, although a minority perform no tests on the basis that their clinical practice would be unaltered if antibodies were present. Positive tests are classed as clinically significant at levels varying from > or = 10% to > or = 50% for direct sperm binding tests (mixed antiglobulin reaction, immunobead test), and ranging from any positive reaction to > or = 1:32 for the microtitre tests (gelatin and tray agglutination tests, microimmobilization test). Strategies for managing affected patients include no intervention, artificial insemination and intrauterine insemination (IUI) using spermatozoa prepared by various techniques, in-vitro fertilization (IVF) with or without increased insemination concentration, and intracytoplasmic sperm injection. Criteria for the latter are diverse, some centres managing all antibody-positive patients this way, while others resort to it only in severe cases or after other treatments have failed. Half of the respondents occasionally or regularly employ steroids, either alone or in conjunction with IUI or IVF. Overall, it appears that much confusion exists as to how best to manage couples presenting with antibody-related infertility.     

Risk factors for antisperm antibodies in infertile men

PROBLEM: The prevalence of anti-sperm antibodies (ASAs) in the general population is 0 to 2%; the prevalence in infertile men is much higher at 7 to 26%. However, the role of ASAs in male infertility remains controversial to date. Although several risk factors for ASA development have been defined (such as testicular torsion, varicocele, cryptorchidism, vasectomy, and genital tract infection), there are no specific indications for ASA testing. METHOD: In order to examine if a single parameter exists identifying patients with elevated ASA titers, serum ASA testing was performed with an enzyme-linked immunosorbent assay (ELISA) in 226 consecutive male patients. The new assay, synchron ELISA (Synelisa) used in our study represents a new type of ELISA without fixation of the sperm surface antigens by formaldehyde or glutaraldehyde. Therefore, the quantitative assay is highly sensitive and reproducible since the structure of sperm surface antigens is not altered by the fixation process. RESULTS: The prevalence of ASAs in this population was 14%, while the prevalence of the control group was 2.5%. Of all factors analyzed only a history of vasectomy, an acute epididymitis, and an abnormal result in the bovine mucus penetration test was associated with elevated ASA titers (P < .001). In addition, we could demonstrate a time related formation of ASAs in men after vasectomy. CONCLUSIONS:     

Differences between intraocular and serum antibody responses in patients with ocular toxoplasmosis

The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is present in many regions of the adult and developing brain as are receptors for PACAP. PACAP stimulates different signalling cascades in neurons, involving cAMP, MAP kinase, and calcium. These characteristics suggest that PACAP may influence neuronal development. Here we have studied the effects of PACAP on mesencephalic dopaminergic neurons using primary cultures from embryonic rats. PACAP increased the number of tyrosine hydroxylase (TH)-immunoreactive neurons, elevated TH protein, and enhanced tritiated dopamine uptake in these cultures. Moreover, PACAP counteracted the effects of 6-hydroxydopamine treatments, which induce cell death of dopaminergic neurons. In situ hybridisation showed that both PACAP and PACAP receptor type 1 are present in developing and adult rat mesencephalon. These results show that PACAP has a neurotrophic action on dopaminergic neurons and partially protects them against 6-OHDA induced neurotoxicity.     

Hybrid antibody mediated veto of cytotoxic T lymphocyte responses

Strategies are being sought that allow the induction of specific tolerance to allogeneic transplants without affecting other immune functions. The so-called veto effect has been described as one such technology where CD8+ cells suppress responses of class I MHC-restricted T-lymphocyte precursors to antigens expressed by those CD8+ veto cells. Yet, veto inhibition will not be able to provide complete tolerance to allogeneic grafts since it only operates on cell populations that express CD8. Other types of cells prevalent in most organs express different tissue-specific antigens that are recognized by alloreactive T-cells. Therefore, complete tolerance to an allogeneic transplant can only be achieved if all cellular components within the graft acquire the immune-inhibitory function. Here, we studied whether the veto effect could be exploited for this purpose nevertheless. We produced a hybrid antibody (HAb) combining a mAb specific for a class I MHC molecule with a soluble CD8 molecule. We found that this HAb specifically and effectively transferred veto inhibition to different stimulator cell populations. Thus, we have developed a strategy that promises to selectively and completely tolerize graft-specific CTLs without affecting normal immune responses.     

Induction of protective CTL responses in newborn mice by a murine retrovirus

The susceptibility of neonates to virus-induced disease is thought to reflect, in part, the immaturity of their immune systems. However, inoculation of newborn mice with low doses of Cas-Br-M murine leukemia virus induced a protective cytotoxic T lymphocyte (CTL) response. The inability of neonates to develop a CTL response to high doses of virus was not the result of immunological immaturity but correlated with the induction of a nonprotective type 2 cytokine response. Thus, the initial viral dose is critical in the development of protective immunity in newborns.     

Induction of pulmonary allergic responses by antigen-specific Th2 cells

The development of pulmonary allergic responses was examined in mice following pulmonary transfer of Ag (conalbumin)-specific Th2 cells. The levels of serum-specific IgE, cellular infiltrates, airway mucus goblet cells, and airway responsiveness were analyzed and compared with those in Ag-sensitized and -challenged mice. Pulmonary transfer of the conalbumin-specific Th2 clone (D10) induced, in an Ag-specific manner, high levels of the Th2 cytokines IL-4 and IL-5 in the bronchoalveolar lavage fluids and mucosal eosinophils, concomitant with an increase in airway responsiveness. The D10 cell-induced responses were seen in the absence of serum specific IgE. In the presence of Ag, the transferred D10 cells not only remained in the lungs, but also increased in number 72 h post-cell transfer. Although significantly higher levels of IL-4 and IL-5 in the bronchoalveolar lavage fluids were found in D10-transferred mice, the levels of pulmonary eosinophilia, mucus goblet cells, and airway responsiveness were significantly lower than those in Ag-sensitized and -challenged mice. These results demonstrate that although Ag-specific activation of Th2 cells at mucosal sites is able to mediate the recruitment of eosinophils and the subsequent induction of airway hyper-responsiveness, the more severe pulmonary allergic responses were observed only in mice sensitized and challenged with Ag.     

Suppression of anti-hapten antibody response in vitro by hapten-carrier conjugates

Production of antibodies was stimulated or suppressed arbitrarily by antigen treatment in vitro of spleens cultured at various time intervals after in vivo immunization. Spleens of mice immunized to the 2,4-dinitrophenyl or (4-hydroxy-3-iodo-5-nitrophenyl)acetyl haptenic determinants produced antibodies in culture when no antigen was applied in vitro. When a conjugate of the hapten to the same carrier employed for priming was given in vitro, an initial reduction of the response was observed, the level of which was dependent on antigen dose. Subsequently, increased amounts of antibodies were measured. In contrast, in vitro exposure to the hapten conjugated to an unrelated carrier resulted in significant reduction of the response for the entire period of the test. This suppressive effect manifested with various carrier proteins (ovalbumin, bovin IgG, bovine and rabbit serum albumin and keyhole limpet hemocyanin), when when applied to cultures in doses which were potentially immunogenic.     

Persistence of Ehrlichia phagocytophila infection in lambs in relation to clinical parameters and antibody responses

Five lambs were infected experimentally with Ehrlichia phagocytophila and examined regularly during the next six months. The lambs all had recurrences of parasitaemia at various times but had a fever on only 21 per cent of these occasions. A reduced number of leucocytes was observed in all the lambs for at least eight weeks. All the lambs were still infected four months after inoculation with E phagocytophila. After six months, blood from four of the five lambs was infective when inoculated into susceptible lambs.     

Epitope-specific antibody and suppression of autoantibody responses against a hybrid self protein

This study addresses the relationship of epitope-specific Ab responses and alternative autoantibody responses in a model system in which an antigenized self protein serves as the carrier for a defined heterologous B cell epitope. Ubiquitin, a nonimmunogenic self protein, was engineered to present heterologous B and T cell epitopes in the recombinant molecule. Fusion to the C terminus introduced a universal T cell epitope from a Mycobacterium tuberculosis Ag. The B cell epitope was created by inserting a 12-residue loop sequence of HIV-1 gp120 at a surface-exposed position of ubiquitin. These modifications preserved the ubiquitin fold, allowing a new conformational epitope to be presented among native self epitopes. Mice immunized with the hybrid protein bearing only the mycobacterial T cell epitope elicited a strong autoantibody response to native ubiquitin. In contrast, antisera elicited against hybrid ubiquitin presenting the HIV B cell epitope reacted specifically with the foreign epitope but not with native ubiquitin. Absence of autoantibody in the response was attributed to poor competition of autoreactive B cells for limiting T cell help. Both types of responses were associated with Th responses to defined epitopes of the ubiquitin hybrid protein. These results may have implications for a tolerance mechanism dependent on B-T cell cooperation.