Numerous studies have evaluated T cell subsets and in vitro IgA synthesis in patients with IgA nephropathy. These reports have resulted in the hypothesis that defective regulation of IgA synthesis is important in the pathogenesis of IgA nephropathy. Baseline immunologic measurements were performed in a clinically well characterized group of 19 pediatric and 13 adult (greater than or equal to 18 years) patients with no macrohematuria or intercurrent infection at the time of study. Mean percentages of OKT3 and OKT4 subsets were significantly decreased for the patients as compared to healthy adult controls. Mean T4:T8 ratios were similar for control and patient groups although 7 patients had T4:T8 ratios greater than 2 SD above the control mean. Unstimulated and pokeweed mitogen stimulated in vitro IgA synthesis was similar for patients and controls. During six episodes of macrohematuria in five patients no significant changes occurred for T cell subset percentages, while mean T4:T8 ratios decreased from baseline. Mean serum concentration of IgA increased during these episodes, although in vitro IgA synthesis remained normal. Our data fail to demonstrate a consistent immunoregulatory abnormality for patients with IgA nephropathy.
The formation of T lymphocyte colonies was studied in 30 normal subjects and 12 patients with suspected abnormalities in immune function. The mean number of colonies per plate in normal subjects was 1.159 +/- 411 which represented a plating efficiency of 0.5-1.0%. When individual cells from colonies of these normal subjects were studied for membrane markers, greater than 90% were E rosette-positive and less than 1% were positive for surface immunoglobulins. Blood lymphocytes obtained from all 12 patients showed diminished colony-forming capacity when compared to normal subjects with a range of 0-311 colonies. Six patients had less than 50 colonies/plate. Colony formation was diminished in some patients who had normal E rosette formation and lymphocyte proliferation in liquid culture. Because of these discrepancies it appears that colony formation is not a direct reflection of E rosette formation and lymphocyte proliferation. Evaluation of T lymphocyte colony-forming capacity may prove useful as an additional in vitro assessment of lymphocyte function.
Abstract Twenty‐two patients, splenectomized 1 to 26 years earlier for hematologic disorders, were studied to determine possible defects in immunologic function or complement levels. Quantitation of B cells and T‐cell subsets revealed slight decreases in the proportions of CD3 and CD4 cells but normal or increased absolute numbers of all cell populations. IgM synthesis in vitro by peripheral blood mononuclear cells was markedly diminished, but IgG synthesis was normal. Fractionation studies, in which various B‐cell‐ and T‐cell‐enriched populations from controls and patients were combined, demonstrated diminished B‐cell function in the patients. Sickle cell patients, who were functionally asplenic, showed similar deficits. Complement levels in splenectomized and sickle cell patients in both the classical and alternative pathways were generally normal. A modest decrease in component H in the alternative pathway in splenectomized and sickle cell patients probably was not clinically significant. In summary, splenectomized patients have a diminished capacity for IgM synthesis that can be attributed primarily to defective B‐cell function. This may be partially responsible for their increased susceptibility to infection by encapsulated organisms.
Interleukin 4 (IL-4) and interferon-gamma (IFN-γ) have been shown to play a role in the regulation of in vitro IgE production by cells from adults. Little information is available regarding the role of these cytokines in influencing IgE production by cells from children. Children ages 3-17 were classified into two groups based upon serum IgE concentrations (>600 U/ml vs. <200 U/ml). Lymphocytes were evaluated for phenotype and IgE production. In vitro IL-4 and IFN-γ production was measured as was the effect of these cytokines on in vitro IgE production by cells obtained from subjects in the two study groups. Children with elevated serum IgE concentrations produced greater amounts of IL-4 than those with lower serum concentrations of IgE. At low dosages of IL-4 (10U) cells from the patients with lower serum IgE concentrations were more sensitive to the effects of IFN-γ, while at higher concentrations of IL-4 (300U) cells from those with higher serum concentrations of IgE were more sensitive to the effects of IFN-γ. The group with higher serum IgE levels had a significantly higher proportion of CD4+ T cells and a greater proportion of cells positive for CD4 and CD29. There are differences in lymphocyte phenotype and IL-4 production in patients with high and normal concentrations of serum IgE. These differences may be important in understanding the basis for different serum IgE concentrations in children.
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