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Biomedical subjects

A D Webster

Publications and source records attributed to A D Webster.

At least 235 records · Page 13Linked to original sources
PubMed1977

Quantitative measurements of T- and B-cell function in "variable" primary hypogammaglobulinaemia: evidence for a consistent B-cell defect.

Improved methods for separating B and T cells have made it possible to assess the functions of these cells. These techniques have been used to study the T dependence of B-cell immunoglobulin production in response to pokeweed mitogen. In the present study they have been used to reinvestigate the pathogenesis of "variable" primary hypogammaglobuliaemia. Twelve patients were studied by separating their B and T cells and culturing them with normal cells. The results show that none of the patients have normal B cells. In cultures containing high ratios of T cells to B cells we have found a marked reduction in B-cell immunoglobulin production both with T cells from normal donors and from patients. T cells from all but one of the patients helped immunoglobulin production and reduced T helper activity was only seen in patients whose B cells were very abnormal. The results suggest that a B-cell defect is the cause of the low serum immunoglobulin in all the patients we have studied.

Adult↗
PubMed1976

Polyarthritis in adults with hypogammaglobulinaemia and its rapid response to immunoglobulin treatment.

Five patients with primary hypogammaglobulinaemia developed a severe polyarthritis that had some features in common with rheumatoid arthritis. Their joint disease could be distinguished from rheumatoid arthritis, however, by the dramatic improvement after gammaglobulin treatment. The arthritis of hypogammaglobulinaemia can, therefore, be included among the few potentially curable polyarthritides.

Adolescent↗
PubMed1976

Enhanced antibody responses in active chronic hepatitis: relation to HLA-B8 and HLA-B12 and porto-systemic shunting.

Titres of antibodies to rubella, measles, smooth muscle, nuclei, and Escherichia coli were examined in relation to the presence of particular histocompatibility antigens in 57 patients with active chronic hepatitis, 8 of whom were HBsAg positive. With the exception of antibodies to E. Coli, the HBsAg-negative patients with HLA-B8 or HLA-B12 had higher titres than those with neither, and antibody titres were highest in the 7 cases with both these histocompatibility antigens. In contrast, E. coli antibody titres were not related to the presence of particular histocompatibility antigens but correlated closely with the degree of portosystemic shunting. None of the HBsAg-positive patients possessed HLA-B8, and titres of all the antibodies were significantly lower than in the HBsAg-negative cases. The increased antibody response in HBsAg-negative patients is likely to be due to a genetically determined increase in immunological responsiveness for which HLA-B8 and HLA-B12 are markers. The results obtained in healthy family members also suggest that this defect in immunoregulation is under polygenic control.

Antibodies↗
PubMed1976

Intracellular immunoglobulin production in vitro by lymphocytes from patients with hypogammaglobulinaemia and their effect on normal lymphocytes.

The ability of peripheral blood lymphocytes from twenty-two patients with late onset (acquired or common variable) hypogammaglobulinaemia to produce immunoglobulin was assessed by the immunofluorescent detection of intracytoplasmic immunoglobulin (Ic-Ig) in cultures stimulated with pokeweed mitogen (PWM). Intracellular immunoglobulin was found in 4-9-26% of cultured cells from eighteen out of nineteen controls. In contrast nineteen out of twenty-two patients with hypogammaglobulinaemia showed values less than 1% and in ten no Ic-Ig was detected. Two of the remaining three patients showed normal values. Lymphocytes from eleven patients showing less than 1% positive cells were selected for mixture experiments. Lymphocytes from five of the eleven patients strongly depressed immunoglobulin synthesis by normal lymphocytes when mixed together in the presence of PWM. However, lymphocytes from these individual patients did not depress immunoglobulin production in all normal controls.

Adolescent↗
PubMed1975

Immunological observations on patients with Lesch-Nyhan syndrome, and on the role of de-novo purine synthesis in lymphocyte transformation.

Three patients with the Lesch-Nyhan syndrome were found to have normal delayed hypersensitivity, peripheral-blood T-lymphocyte counts, lymphocyte responses to P.H.A., and serum IgM, IgA, and IgE levels. However, the percentages of B-lymphocytes, IgG levels, serum-isohaemagglutinin titres, and lymphocyte responses to pokeweed mitogen (P.W.M.) were subnormal. These observations suggest that activity of the salvage pathway of purine synthesis catalysed by hypoxanthine-guanine phosphoribosyl transferase (H.G.P.R.T.) is not required for the responses of T-lymphocytes to mitogenic or antigenic stimulation, but may contribute to the proliferation and function of B lymphocytes. The major role of the de-novo pathway of purine synthesis in human lymphocyte responses to mitogenic or antigenic stimulation is shown by the effects of inhibitors of this pathway, including immunosuppressive agents, and by the effects of congenital deficiency or inhibition of adenosine deaminase.

Adenosine Deaminase↗
PubMed1975

Dichotomy between immunoglobulin synthesis by cells in gut and blood of patients with hypogammaglobulinaemia.

Eleven of fifteen patients with late-onset hypogammaglobulinaemia were found to have significant numbers of immunoglobulin-containing cells in the lamina propria of the gut. In six of them typical plasma cells were detected. In contrast the blood lymphocytes of only two of these patients could be induced to synthesise immunoglobulin by stimulation with pokeweed mitogen in vitro. Moreover, one patient in whom immunoglobulin-containing cells and plasma cells were detected in the rectum and jejunum failed to show similar cells in a peripheral lymph-node even after immunisation with pneumococcal polysaccharide type-III antigen in the drainage area of the node. It is possible, therefore, that the gut is a privileged site for the differentiation of B cells in these patients.

Adult↗
PubMed1974

Escherichia coli antibody: a screening test for immunodeficiency.

Six patients suffering from recurrent chest infections were found to lack antibodies to a pooled antigen obtained from six different serotypes of commensal Escherichia coli bacteria. All had normal serum IgG concentrations, but five subsequently benefited from regular gammaglobulin injections. We suggest that the absence of such E. coli antibodies usually indicates a clinically significant defect in antibody production. This simple screening test is of use in the diagnosis of primary and secondary immunodeficiency disorders.

Adolescent↗