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Biomedical subjects

C Cunningham-Rundles

Publications and source records attributed to C Cunningham-Rundles.

At least 109 records · Page 6Linked to original sources
PubMed1982

Naturally occurring autologous anti-idiotypic antibodies. Participation in immune complex formation in selective IgA deficiency.

50% of individuals of selective IgA deficiency have high serum titers of antibody to bovine proteins, and high levels of circulating immune complexes that contain bovine antigens. Because in animal studies, immunization with antigen-antibody complexes is a very effective means of producing anti-idiotypic antibodies, we sought such autoantibodies in two sera known to have large amounts of anticasein. After IgG isolation and two-stage affinity chromatography, IgG-like material (molecular weights of H and L chains on SDS-PAGE), with binding activity for the F(ab')2 of anticasein were isolated from both sera. Pooled human gamma globulin or IgG myeloma proteins did not inhibit binding of specific anti-anticaseins to the corresponding anticasein, but sodium caseinate did block this binding (by 80 and 95%) indicating that most of these autoantibodies have affinity for the casein-binding site. Naturally occurring anti-idiotypic antibodies have been difficult to conclusively demonstrate in human sera; consequently, these experiments provide evidence of a unique model which may be used to explore the network theory of immunoglobulin regulation in humans.

Antibodies, Anti-Idiotypic↗
PubMed1982

Three distinct stages of B-cell defects in common varied immunodeficiency.

B-lymphocyte function of 15 patients with primary common varied immunodeficiency or related disease were examined. All patients had low serum levels of IgM, IgG, and IgA, but 12 of 15 patients had nearly normal numbers of peripheral blood B lymphocytes. Mononuclear cells and B cells from peripheral blood were assayed for B-cell mitogenic responses to anti-Ig mu chain antibodies or to Staphylococcus aureus strain Cowan I (referred to as Cowan I), and for differentiation to Ig-secreting cells of IgM, IgG, and IgA classes in the presence of Cowan I and pokeweed mitogen or T-cell factor. The patients all showed profound B-cell defects in one or more of the assays and could be divided into three approximately equal groups based on their responses. The first group showed normal proliferation in response to the two B-cell mitogens and near normal numbers of IgM-secreting cells but no IgG- or IgA-secreting cells. B cells in the second group showed proliferative responses to Cowan I or anti-mu, but no differentiation to Ig-secreting cells. The third group had no B-cell proliferative responses or differentiation in our assays. In several patients from each group, (i) helper T cells were functional in Ig-secreting-cell responses with purified normal B cells, (ii) patient T cells did not significantly suppress formation of Ig-secreting cells by normal cells in coculture, and (iii) removal of T cells with addition of T-cell-replacing factor, or partial removal of monocytes, did not alleviate any of the defects. These studies show that primary B-cell defects in common varied immunodeficiency occur at several levels, probably representing blocks at different stages of differentiation.

Adolescent↗
PubMed1982

Impaired proliferative response to B-lymphocyte activators in common variable immunodeficiency.

The cell-mediated immune responses of 39 patients with common variable immunodeficiency (CVI) were studied in vitro, using Staphylococcus aureus and Escherichia coli prepared as whole cells and Candida albicans extract. These microbial activators wee found to require intact B-lymphocyte function for normal proliferative response. The patient group was observed to have significantly depressed lymphocyte responses compared wit those of controls studied in parallel (P less than 0.01). Negative lymphocyte response to one activator and strongly positive response to another were found in individual patients. Examination of patients' lymphocyte response to S. aureus and E. coli in association with serum IgG levels demonstrated that a rough correlation could be drawn, showing that patients with serum IgG less than 125 mg/dl had markedly lower (P less than 0.01) lymphocyte responses than those with serum IgG greater than 300 mg/dl. No similar correlation with phytohaemagglutinin activation was observed. Since depressed lymphocyte responses did not correlate with reduced B-cell number in these patients, intrinsic B-lymphocyte deficiency was indicated. These preparations of microbial activators are potentially useful tools in exploring lymphocyte subpopulation functions in primary immunodeficiency diseases.

Adolescent↗
PubMed1982

Chronic granulomatous disease and selective IgA deficiency.

The clinical and laboratory features of a child with chronic granulomatous disease (CGD) and IgA deficiency and his family are presented. Bactericidal and NBT dye reduction studies confirmed the diagnosis of CGD in the patient and the carrier state in the mother. No other family member had IgA deficiency. The manifestations of the IgA deficiency include multiple autoimmune antibodies, progressive pulmonary dysfunction but no gastrointestinal or rheumatoid symptoms. The etiology of the IgA deficiency appears to be a failure in terminal B cell differentiation as evidenced by the presence of normal numbers of IgA bearing cells detected by a fluorescent monospecific antisera, a normal profile of T cell subpopulations, normal responses to the mitogens PHA, Con A, PWM, and antigens C. albicans, E. coli, and S. aureus, and the absence of suppressor cell activity in co-culture assays. The significance of the association of these two disorders is discussed.

Adult↗
PubMed1982

Immune complexes containing H-Y antigen and maternal IgG in cord serum.

Increased levels of immune complexes are more frequently detected in the serum of newborn males than they are in the serum of newborn females. In one survey of 545 newborns, 21 of 26 (81%) of the babies with high levels of immune complexes in cord serum were boys (Farber, Cambiaso & Masson, 1981). To evaluate the hypothesis that this was due in some cases to the synthesis by the mother of antibodies directed against the 'male-specific' H-Y antigen, we tested for presence of IgG antibodies bound to H-Y antigen in serum samples from 263 newborns including 124 girls and 139 boys. Sera from five of the 10 male newborns with high levels of immune complexes contained IgG bound to H-Y; none of the sera from newborn girls had detectable amounts of those immune complexes; and sera from women who had borne males manifested higher levels of IgG reactive with sources of soluble H-Y than sera from women who had borne females.

Adult↗
PubMed1981

Severe acquired immunodeficiency in male homosexuals, manifested by chronic perianal ulcerative herpes simplex lesions.

Four homosexual men presented with gradually enlarging perianal ulcers, from which herpes simplex virus was cultured. Each patient had a prolonged course characterized by eight loss, fever, and evidence of infection by other opportunistic microorganisms including cytomegalovirus, Pneumocystis carinii, and Candida albicans. Three patients died; Kaposi's sarcoma developed in the fourth. All were found to have depressed cell-mediated immunity, as evidenced by skin anergy, lymphopenia, and poor or absent responses to plant lectins and antigens in vitro. Natural-killer-cell activity directed against target cells infected with herpes simplex virus was depressed in all patients. The absence of a history of recurrent infections or of histologic evidence of lymphoproliferative or other neoplastic diseases suggests that the immune defects were acquired.

Adult↗
PubMed1981

Evolutionary conservation of surface molecules that distinguish T lymphocyte helper/inducer and cytotoxic/suppressor subpopulations in mouse and man.

We describe the biochemical properties and cell surface distributions of three human T cell antigens (Leu-1, Leu-2a, and Leu-2b) which we postulate to be the homologues of the Lyt-1, Lyt-2, and Lyt-3 antigens that distinguish functional T cell subsets in the mouse. Leu-l, like Lyt-1, is on all thymocytes and peripheral T cells and is present in greater amounts on the helper/inducer subset than on the cytotoxic/suppressor subset. Both antigens increase in parallel fashion during T cell maturation in the thymus and each antigen is carried on a single 67,000-molecular weight (relative) (M(r)) polypeptide chain. Surprisingly, Leu-1 and Lyt-1 each are also expressed in readily detectable amounts on some B celI Ieukemias but not detectably so on normal B cells. Leu-2a and Leu-2b are antigens found only on suppressor/cytotoxic cells in the human and are very similar to the murine Lyt-2 and Lyt-3 antigens. In both species, the two antigens are on the same disulfide- linked multimeric molecules. Disulfide-bond reduction in both species yields subunits of similar size and charge. Lyt-3 and Leu-2b are extremely sensitive to trypsin digestion on viable cells whereas Lyt-2 and Leu-2a are much less so. A different membrane antigen, Leu-3, is an exclusive marker of the helper/inducer subset in man. No mouse homologue for this 55,000-M(r) protein is known. The maintenance of the homologous molecules on functionally distinct T cell subpopulations in two evolutionarily distant species suggests that the Lyt and Leu antigens perform essential functions for the cells on which they are found.

Animals↗
PubMed1981

The identification of specific antigens in circulating immune complexes by an enzyme-linked immunosorbent assay: detection of bovine kappa-casein IgG complexes in human sera.

Circulating immune complexes have been implicated in the development of tissue injury in many chronic disease states, but in most instances the inciting antigens have not been identified. This report describes the development of a sensitive enzyme-linked immunosorbent assay which can be used to screen rapidly and simultaneously the immune complexes of numerous sera for the presence of a suspected antigen. The prototype antigen sought here was kappa-casein, a frequent participant in immune complex formation in IgA deficiency and in atopic diseases. The enzyme-antibody conjugate described here can detect as little as 0.11 ng/ml of kappa-casein; for immune complexes formed in vivo or in vitro, one can distinguish circulating complexes containing casein from complexes not containing this antigen. Using this reagent, a major antigen in the immune complexes of hypogamma-globulinemic patients treated with intravenous gamma-globulin was unexpectedly identified as kappa-casein. This method of specific immune complex analysis is suggested as a practical and effective approach to the elucidation of the antigenic constituents of immune complexes found in many diseases.

Absorption↗
PubMed1981

Defective cellular immune response in vitro in common variable immunodeficiency.

Mononuclear cells from 39 patients with hypogammaglobulinemia of the common variable type were analyzed for in vitro proliferative response to a panel of cell activators in order to examine the lymphocyte response to mitogens and to study the capacity to generate an immunologically specific secondary response. Patient lymphocyte response to phytohemagglutinin and concanavalin A was found to be significantly lower than that of controls studied in parallel (P less than 0.01), and low response did not correlate with T-lymphocyte number. Response to pokeweed mitogen was significantly lower than that of controls (P less than 0.01), but response to zinc, tested in a few patients, was normal. Strong depressions of patient lymphocyte proliferative responses to Candida albicans, Escherichia coli, and Staphylococcus aureus were observed (P less than 0.01); all of these microbial activators require intact B-cell function for maximum response. Repeated testing of individual patients indicated that poor lymphocyte response could be consistently observed. Examination of change in vitro lymphocyte response during clinical course and disease management showed that a consistent pattern of intrinsic lymphocyte functional deficiency could be demonstrated.

Adolescent↗
PubMed1981

Autoimmunity in selective IgA deficiency: relationship to anti-bovine protein antibodies, circulating immune complexes and clinical disease.

To test the possibility that autoimmunity could be related to increased levels of anti-bovine antibodies and/or circulating immune complexes in selective IgA deficiency, we studied the sera of 30 consecutive patients for the quantitative level of antibody to bovine milk, the presence of antigen--antibody complexes and 10 selected autoantibodies. Higher titres of anti-milk antibody and circulating immune complexes were to be correlated with positive serological tests of autoimmunity in these patients, and rheumatoid arthritis (three cases) and neurological disease (four cases) were found in individuals who had both milk precipitins and circulating immune complexes. We suggest that the chronic excessive permeability of the gastrointestinal tract in selective IgA deficiency may permit the excessive absorption of many food proteins, leading to the formation of antigen--antibody complexes and autoimmunity.

Adolescent↗
PubMed1980

Isolation and partial chemical characterization of the IgG Fc receptor of human T lymphocytes and production of an antiserum.

We report here the isolation of an IgG Fc receptor from normal human T lymphocytes. The purified receptor has a nonreduced and a reduced component of molecular weights 120,000 and 60,000, respectively, and it was functionally active in the in vitro blocking of rosette formation between T lymphocytes and IgG-coated ox erythrocytes. An antiserum raised to the Fc receptor and an isolated F(ab')2 fragment of this antiserum, also blocked rosette formation between T cells and IgG-coated ox erythrocytes. In contrast, rosette formation between T lymphocytes and IgM-coated ox or sheep erythrocytes was not blocked by the F(ab')2 fragment, demonstrating the marked specificity of this antiserum for the IgG Fc receptor. In addition, this antiserum did not block the Fc receptors of non-T cells, indicating that the T-cell IgG Fc receptor has unique antigenic determinants not shared with B cells.

Electrophoresis, Polyacrylamide Gel↗
PubMed1980

Selective IgA deficiency and neoplasia.

From the Immunodeficiency Cancer Registry, it has appeared that there is an increasing frequency of neoplasia in individuals who have a selective absence of serum IgA. Approaching this question from another point of view, we have found that of 4,120 sera drawn in this cancer-oriented hospital, 12 sera had a total absence of IgA and 3 additional sera had less than 10 mg/dl. The incidence of IgA deficiency in a cancer hospital is thus 1 : 342 or 1 : 273, which is statistically similar to that previously found for other patient groups studied in the USA (average of two studies, 1 : 418), but it is substatistically increased over the incidence of IgA deficiency found in normal blood donors (average of five studies 1 : 1,677). Analysis of these sera by diagnostic categories showed that of 1,517 sera of patients with lymphoproliferative disorders, 6 were IgA deficient (frequency 1 : 253), and of 249 sera of patients with gastrointestinal neoplasm, 2 were IgA deficient (frequency 1 : 125). We conclude that, in the absence of IgA, certain organ systems, the gastrointestinal and lymphoid tissue may be at increased risk for malignant change and that the protective, anti-neoplastic role of IgA requires investigation.

Adult↗
PubMed1980

Quantitation of circulating immune complexes in serum by Raji cells using an enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay (ELISA) for the quantitation of immune complexes in sera has been developed using Raji cells. In this assay the Raji cell-adherent complexes are detected by an alkaline phosphatase-conjugated rabbit anti-human IgG and the results are obtained by spectrophotometric measurements of the concentration of yellow colour produced after the enzyme's substrate, p-nitrophenyl phosphate, is added. This assay is as sensitive and reproducible as the Raji cell radioimmune assay using 125I, as it can detect as little as 16 micrograms of immune complex equivalent to heat-aggregated IgG/ml in serum samples. This method is inexpensive, convenient and most importantly, avoids the biohazards of using an isotope.

Antigen-Antibody Complex↗
PubMed1979

Selective IgA deficiency and circulating immune complexes containing bovine proteins in a child with chronic graft versus host disease.

We have previously shown that a selective absence of serum and secretory immunoglobulin A (IgA) may lead to the development of circulating immune complexes which appear to contain bovine milk antigens. We report here that high levels of circulating immune complexes were found in the serum of a child who was treated for severe combined immunodeficiency by bone marrow transplantation but in whom the IgA-producing cells subsequently failed. As increasing amounts of complexes appeared over a two year period, the child had a parallel progression of an apparent chronic graft versus host disease including a Sjögrens syndrome and scleroderma. Very large amounts of complexes were eventually formed but the level fell 77 per cent after milk was excluded from the diet. Chemical studies on the complexes showed that the majority of complexes did contain bovine milk proteins, and fluorescence antibody staining of skin biopsy samples showed the presence of dense deposits of bovine casein in the dermis. The relationship between bovine protein-antigen antibody complexes and the chronic graft reaction remains uncertain.

Antibodies↗