Autoantibody panel screening in recurrent miscarriages.

PROBLEM: Antiphospholipid autoantibodies (aPL), antithyroid antibodies and anti-extractable nuclear antigens (anti-ENA) have all been reported to be associated with recurrent miscarriages (RM) and infertility. However, this association remained controversial. MATERIALS AND METHODS: Fifty-eight women with impaired fertility (38 women with RM and 20 women with infertility, but no miscarriages) and 28 control parous women were screened for seven autoantibodies [antithyroglobulin (aTG), antithyroid peroxidase (aTPO), anticardiolipin (aCL), antiphosphatidyl-serine (aPS), antiprothrombin antibodies (aPT), anti-beta 2 glycoprotein 1 (abeta2GP1), and anti-ENA]. There was no evidence for autoimmune diseases in the patients or the control. The analysis was also performed with several panels of autoantibodies, each of which contained two or more autoantibodies. RESULTS: Anti-TPO was the only antibody to be associated with RM (P = 0.01). A significant association was found between RM, and autoantibodies in the 'aTG + aTPO + anti-ENA' or 'aTG + aTPO' panels. The 'aTG + aTPO + anti-ENA' panel was also associated with RM when the analysis was performed only on 17 women who had secondary infertility: 10 from the 38 women with RM, and seven from the 20 women with infertility and no miscarriages. A significant association (P < 0.001) was also apparent between anti-CL and anti-PS and infertility compared with the 28 control women. CONCLUSIONS: RM was associated with autoantibodies to aTPO and the combined panel of aTPO, aTG and anti-ENA, but not with aPL. aPL were associated with infertility.

Production of IL 2 and IFN-gamma by T cells from malaria patients in response to Plasmodium falciparum or erythrocyte antigens in vitro.

T cells from patients acutely infected with malaria exhibit a disease-related stimulation of DNA synthesis in response to Plasmodium falciparum antigen in vitro. This response is weak and short-lived, suggestive of induction of suppressor mechanisms. Exogenous T cell growth factor (IL 2) that was added to antigen-stimulated T cell cultures enhanced proliferation in antigen-responsive cultures, indicating that the lymphocytes expressed IL 2 receptors. In contrast, the addition of IL 2 to cultures that did not respond to antigen had no effect. Antigen-responsive cultures contained endogenous IL 2 as well, and the antigen-induced lymphocyte proliferation was correlated with IL 2 production. However, the results suggested that IL 2 production by the patients' T cells was insufficient or actively shut off, and that this was responsible for the premature cessation of their DNA synthesis. Supernatants from 60% of the T cell cultures treated with malaria antigen and from 30% treated with RBC ghost antigen contained interferon-gamma (IFN-gamma), as determined by a cytopathic effect inhibition assay combined with acid treatment and antibody neutralization or by an IFN-gamma-specific ELISA. There was no obvious correlation between antigen-induced lymphocyte proliferation and the presence of IFN-gamma in the culture supernatants. A high IFN-gamma activity was also seen in antigen-treated cultures from P. falciparum-immune donors living in highly endemic malaria areas. In contrast, no IFN-gamma was found in supernatants of antigen-treated T cells from healthy donors or patients with Plasmodium vivax malaria. Thus, the IFN-gamma activity of these cultures appears to reflect the presence of antigen-reactive T cells and may be useful as a sensitive indicator of cellular immunity in P. falciparum malaria.

Analysis of clinical specimens by hybridisation with probe containing repetitive DNA from Plasmodium falciparum. A novel approach to malaria diagnosis.

The capacity of a DNA probe containing cloned repetitive sequences from Plasmodium falciparum to identify malaria-infected blood samples was tested with a spot hybridisation assay. Parasitaemia levels of 0.001% could be detected in 50 microliters blood from patients. The probe correctly diagnosed P falciparum infection in patients from different continents and appeared to be specific for P falciparum, since it did not cross-react with three other Plasmodium species tested.

Positive correlation between degree of parasitemia, interferon titers, and natural killer cell activity in Plasmodium falciparum-infected children.

Natural killer (NK) cell activity and interferon levels have been measured in the peripheral blood of children acutely ill with Plasmodium falciparum infection. The NK cell levels were found to be raised in the malaria-infected children, with a positive correlation between the degree of parasitemia and lytic activity. Comparatively high titers of antiviral activity was discovered in sera from the majority of P. falciparum-infected children, again positively correlating with the degree of parasitemia and NK levels. The characteristics of the antiviral factor indicated alpha-type interferon to be the dominating agent involved. Addition of exogenous interferon in vitro potentiated the NK levels of PBL from normal children while having no significant impact on cells from malaria-infected children.