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We tested for infection with hepatitis C virus (HCV) in 58 patients affected by humoral immunodeficiencies: 43 common variable immunodeficiency (CVI), two hyper IgM syndrome (HIM), two IgG subclass deficiency, four ataxia-telangiectasia (AT), and seven X-linked agammaglobulinaemia (XLA). While the assessment of serum specific HCV antibodies in some of these patients was not informative because of the impairment in specific antibody production, the reverse transcriptase polymerase chain reaction (RT-PCR) assay used to detect serum HCV RNA was a useful method for diagnosing infection. We found that 38% of late onset hypogammaglobulinaemic patients (CVI, HIM or IgG subclass deficiency) had evidence of HCV infection. HCV infection was not detectable in patients with XLA or AT. The majority of our patients had persistent viraemia, and those who underwent liver biopsy showed histological findings of chronic hepatitis. Moreover, we could demonstrate in vitro that eight of 18 HCV-infected patients were actively producing anti-HCV antibodies, despite their impaired antibody production. The high rate of HCV infection in hypogammaglobulinaemic patients could be related to several nosocomial routes of transmission, including intravenous immune globulin administration. Despite the persistent viremia only two patients had cirrhosis and none had hepatocarcinoma.

We measured the in vitro production of interferon-gamma (IFN-gamma) in five cases of hyper-IgE syndrome (HIgE), induced by mitogens, calcium ionophores and phorbol ester. The biosynthesis of IFN-gamma was severely reduced or undetectable in HIgE, while it was near normal in most atopic patients. The in vitro spontaneous production of IgE was increased overall in HIgE patients, although no correlation was found with serum IgE levels. Recombinant interleukin-4 (IL-4) induced a further increase in IgE synthesis, and its effect was totally antagonized by recombinant IFN-gamma; the same pattern of response was also observed in atopic subjects with high production of IgE. IFN-alpha synergized with IL-4 on IgE synthesis, whereas recombinant IL-6 gave opposite changes in individual cases tested. We propose that IFN-gamma deficiency may be responsible for some of the features of HIgE patients, including IgE levels and infections.

We tested the hypothesis that serum factors present in Crohn's disease interfere with the process of lymphocyte activation. The mitogen-induced proliferation and the expression of early activation antigens by normal lymphocytes cultured in the presence of either Crohn's disease sera or sera from different controls were evaluated. The mitogen-induced proliferation was significantly impaired in the presence of Crohn's disease sera. These sera markedly inhibited the mitogen-induced interleukin-2 receptor (IL-2R) expression (48% inhibition), while the effect of sera on the expression of the transferrin receptor and the 4F2 antigen was much less pronounced. Diafiltration experiments showed that the inhibitory effect was confined to a 30-50-kD serum fraction. Such a serum property was not related to the patients' disease activity and disappeared after surgical removal of the affected bowel. The capability of inhibiting the mitogen-induced IL-2R expression was not restricted to Crohn's disease and was observed with sera from other inflammatory and neoplastic gastrointestinal disorders. This study indicates that a marked inhibition of the IL-2R is a mechanism underlying the immunosuppressive property of the serum in Crohn's disease and in other gastrointestinal conditions.

A simple two-step method for the detection of specific antigen within immune complexes is described. The immune complexes are precipitated from serum by polyethylene glycol, dissociated by incubation in acid pH buffer and adsorbed onto the surface of polystyrene tubes. The antigen is detected by the binding of a radiolabelled affinity-purified specific antibody. The assay can detect the antigen within both antigen- and antibody-excess immune complexes of any immunoglobulin class, and can also allow semiquantitative comparison of different samples. Immune complexes containing food protein antigens after eating have been found in the serum of both normal subjects and atopic patients; the latter group showed higher mean levels of antigen-specific immune complexes. The method can be adopted for large-scale screening of clinical samples for suspected antigens if suitable antisera are available.

Circulating immune complexes were detected in sera of patients with both localized and generalized onchocerciasis by a 125I-Clq binding assay but not by the IgG latex agglutination inhibition method. Gel filtration of sera demonstrated high molecular weight Clq-reactive material(greater than 2 x 10(6) Daltons) which contained IgM but no IgG. Antibody titres to Onchocerca volvulus antigen were higher in patients with generalized disease than in those with the localized form. The lack of correlation between antibody titres and levels of immune complexes suggests that these immune complexes contain antigens other than those derived exclusively from the parasite. Although few of the symptoms of this disease are likely to be due to deposition of circulating immune complexes, the depression of delayed hypersensitivity reactions to the parasite found in patients with generalized onchocerciasis may be due to IgM immune complexes exerting an immuno-regulatory role on T cell function.

Thymidine uptake in PHA-stimulated culture of cord blood cells from smoking mothers is greater than that from non-smoking mothers. There was no such difference when separated lymphocytes were studied; this suggests that smoking suppresses a suppressor cell. No difference was detected in haemoglobin, immunoglobulins, transferrin, cell counts, E-rosette counts and leucocyte mobility.

The intestinal absorption of ovalbumin and beta-lactoglobulin was measured in Hooded Lister rats which had previously been made allergic to ovalbumin, and in unimmunized controls. The antigens were introduced both together and separately into closed intestinal loops. Absorption of free ovalbumin, but not beta-lactoglobulin, was reduced in rats with anti-ovalbumin antibody, demonstrating antigen-specific immune exclusion despite the presence of reaginic antibody. In contrast, the absorption of beta-lactoglobulin was enhanced by the presence of ovalbumin in rats with IgE anti-ovalbumin, but not in unimmunized controls. These results suggest that macromolecular absorption may be increased in an antigen non-specific way in food allergy.

We have selected 11 patients with primary immunodeficiency disorders predominantly affecting T lymphocyte function (four with ataxia-telangiectasia (AT), four with common variable immunodeficiency (CVI) and one each with Wiskott-Aldrich syndrome, hyper-IgE syndrome and combined immunodeficiency) with defective gamma interferon (IFN-gamma) production in vitro. Induction with phytohaemagglutinin showed low interleukin 2 (IL-2) production concomitant with reduced IFN-gamma titres. However the addition of 10 U/ml of rIL-2 to cultures stimulated with staphylococcal enterotoxin B or galactose oxidase failed to restore IFN-gamma production in defective cases. IFN-gamma was titrated by both bioassay and immunoradiometric assay, ruling out the possible release of inactive or altered IFN-gamma molecules. Normal levels of IFN-gamma were found in patients of patients with AT, as well as in two AT and two CVI cases, demonstrating heterogeneity of defects within these syndromes. Soluble inhibitors or cellular suppression of IFN-gamma were not observed in mixing experiments. The possibility that defective interaction between accessory cells and T lymphocytes might account for the poor response to the inducing agents was ruled out as no IFN-gamma was produced using a calcium ionophore--which bypasses this step--in seven patients with absolute IFN-gamma deficiency.