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Is there any evidence for immunologically mediated or immunologically modifiable early pregnancy failure?

PURPOSE: Human reproduction is an inefficient process. There is a high rate of loss of early pregnancies, often before the mother (or physician) knows she is pregnant. Genetic abnormalities can explain much of the wastage, but can it explain all of the failures? As embryos bear paternal and embryonic antigens foreign to the maternal immune system, could some otherwise normal embryos be "rejected"? METHODS: Critical review of existing data. RESULTS AND CONCLUSIONS: Otherwise normal embryos can fail prior to implantation, at implantation, in the periimplantation period as occult/chemical pregnancies, and as clinically evident miscarriages. The maternal immune system and its products (e.g., cytokines) can have innocent bystander effects, and a good case for direct recognition and "rejection" can also be made. The tools needed for accurate clinical diagnosis of such situations require further development and validation. Deliberate modification of the maternal host defence system can improve the chance of success, but the best evidence for efficacy of immunotherapeutic interventions is the situation of recurrent spontaneous abortions, which constitutes only a small percentage of losses. There is also evidence of clinical efficacy for several types of treatment to improve implantation and early pregnancy success.

Abortion, Habitual↗

Molecular and immunological characterization of hr44, a human ocular component immunologically cross-reactive with antigen Ov39 of Onchocerca volvulus.

Structural similarities between host self-antigens and infectious organisms may be involved in the expression of autoimmune reactivity and development of autoimmune disease. The unique eye pathology associated with Onchocerca volvulus infection, particularly the development of posterior segment lesions, may be promoted by such autoreactive responses. Ov39 is a parasite-derived antigen that has been shown previously to be antigenically cross-reactive with a 44,000-M(r) host ocular component. A clone, designated hr44, was isolated from a cDNA library of human retina by immunoscreen using serum to Ov39. A monoclonal antibody raised to Ov39 also reacted with hr44 and gave evidence for a shared conformational epitope. The primary structure analysis showed that identities between the antigens are limited and confined to small peptides. The cross-reactivity between the antigens appears to involve T cells, since Ov39-specific T cells can be stimulated by hr44, a neural-specific antigen. Based on secondary structure prediction, hr44 has the typical features of a membrane-associated type I antigen with an amino-terminal extracellular domain. mAbs and antisera localized the antigen in the optic nerve, neural retina, retinal pigment epithelium, as well as the epithelial layers of ciliary body and iris.

Amino Acid Sequence↗

Immunological unresponsiveness to hepatic allografts in rats. Immunological reactivities of the recipient to donor antigens.

Wistar (RT1bv1) rats transplanted orthotopically with ACI (RT1a) livers survive indefinitely without any immunosuppression, while heterotopic heart grafts or skin grafts are rejected acutely in this combination. Levels of alkaline phosphatase after liver allografting remain significantly higher than those found in controls receiving syngeneic grafts. We studied changes in immune responsiveness in rats receiving liver grafts. Local graft-versus-host reactivity was present at all times assayed. Delayed type hypersensitivity reactions were already positive 2 weeks after liver transplantation and increased in strength. Liver graft-bearing rats were subsequently grafted with donor or third-party skin. Third-party skin grafts survived significantly longer on liver-grafted rats than on untreated controls when grafted within the first week after grafting. Donor-type skin grafts survived longer than controls when grafted within the first 4 weeks after liver grafting, although the skin grafts were eventually rejected. Donor-type skin grafted more than 8 weeks after liver grafting was rejected acutely. In an adoptive transfer assay, ACI hearts survived significantly longer in Wistar rats given serum from Wistar donors 2-4 weeks after ACI liver grafts than in untreated controls. On the other hand, spleen cells obtained at any period after liver grafting were not capable of prolonging cardiac allograft survival after transfer to syngeneic recipients. Thus cellular responses to ACI antigen are not changed during the life-span of liver-grafted animals. Evidence suggests that a serum "enhancing" factor protects the donor liver from rejection in the initial period after liver transplantation. The long-term acceptance of liver grafts is discussed.

Animals↗

Evaluation of immunologic markers in cervicovaginal fluid of HIV-infected and uninfected women: implications for the immunologic response to HIV in the female genital tract.

We analyzed 21 cervicovaginal lavage (CVL) specimens from 19 women participating in the Women's Interagency HIV Study to characterize levels of antibody, cytokine, and complement and to determine associations between these levels and stage of the menstrual cycle, HIV status, and the presence of concurrent genital infection and genital dysplasia. Sixteen samples were collected from HIV-infected women and five from high-risk HIV-seronegative women. CVL fluid was assayed for levels of IgG, secretory IgA (s-IgA), interleukin 2 (IL-2), IL-10, IL-6, tumor necrosis factor alpha (TNF-alpha), IL-1beta, interferon gamma (IFN-gamma), C3, C1q, and C4. Women with HIV were more likely to have cervicovaginal dysplasia (9/16 vs. 0/5; p = 0.027) but were not more likely to have concurrent vaginal infection (10/16 vs. 2/5; p = 0.38). Antibody, cytokine, and complement were detectable in all samples, although not all samples had measurable IL-10, C3, or C4. HIV-infected women demonstrated a trend toward higher levels of IFN-gamma than did uninfected women (p = 0.098); no differences were noted in other parameters. HIV-infected women with vaginal infections had significantly higher CVL levels of IgG (p = 0.023) and IFN-gamma (p = 0.02) than did HIV-infected women without genital infections. HIV-infected women with cervicovaginal dysplasia were found to have higher levels of IL-1beta (p = 0.045) and IFN-gamma (p = 0.039) than those without. Analysis of the HIV-infected cohort by CD4 cell count revealed higher levels of IgG and IFN-gamma in CVL from women with lower CD4 cell counts, although these differences were not statistically significant. Higher levels of proinflammatory cytokines in CVL fluid of women with genital infection or cervicovaginal dysplasia may affect local HIV replication and may influence the risk of acquisition or transmission of HIV for women with these underlying conditions.

Adult↗

Effects of acute injection of methylprednisolone in man on immunological and non-immunological histamine release from leucocytes and its potentiation by interleukin-3.

We investigated the effects of intravenous injection of methylprednisolone (MPR) compared with placebo (saline) on ex vivo leucocytic histamine release in eight healthy volunteers. All subjects received in a randomized and a single-blind manner the placebo and MPR, 20 mg and 125 mg, each injection given in 2 week intervals. On each occasion blood samples were taken just before and 24 h after the intravenous injection to determine circulating leucocyte counts and leucocytic histamine release induced by anti-IgE (1/2000) and FMP (Formyl-Methionyl-Phenylalanine) (10(-5) M) and its modulation by IL-3 (2 ng/ml). MPR 20 mg and 125 mg significantly increased circulating leucocyte counts (P < 0.05 and P < 0.001 respectively) but decreased leucocytic histamine content (P < 0.05 and P < 0.001 respectively) by 24 h. Placebo had no effect. As for circulating basophils, after 24 h they were decreased by 125 mg MPR (P < 0.05) but increased by 20 mg (P < 0.05). Anti-IgE-induced HR was significantly inhibited by 125 mg MPR (P < 0.05) but not by 20 mg MPR or by the placebo. In contrast, neither MPR (20 mg and 125 mg) nor placebo significantly reduced FMP-induced HR. The strong potentiation by IL-3 of HR evoked by anti-IgE and FMP at baseline (P < 0.001) persisted 24 h after injection of MPR or placebo (P < 0.001 except P < 0.05 for anti-IgE-induced HR after 125 mg MPR).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A clinical and immunological study of allergy to hen's egg white. IV. Specific IGE-antibodies to individual allergens in hen's egg white related to clinical and immunological parameters in egg-allergic patients.

Different subgroups of egg-allergic patients were established according to differences in allergic symptoms provoked by hen's egg white, total IgE-level, RAST (radioallergosorbent test) results to egg white, and age. In each group the pattern of specific IgE-antibodies to individual allergens in the egg white, determined by means of crossed radioimmunoelectrophoresis (CRIE), was compared with the pattern in a control group. The RAST value to egg white was found to exert the strongest influence on the CRIE results. A few statistically significant differences in CRIE results to certain allergens were also observed in other pairs of subgroups of egg-allergic patients. Possible explanations for this are discussed. It was concluded that CRIE studies of allergens in mixed protein solutions, using a series of sera from allergic patients, will most probably give the same results and the same classification of the allergens independent of the characteristics of the patients from which the sera were collected. However, it should be emphasized that the CRIE series must include a sufficient number of patients with high RAST values to the allergen in question. Otherwise some allergens may be missed and the classification of the allergens may be different.

Adolescent↗