Profiles of immunoregulatory cytokine production in vitro in patients with IgA nephropathy and their kindred

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Abstract
SUMMARY: We hypothesized that the altered immunoglobulin synthesis and/or lymphocyte function apparent in patients with IgA nephropathy (IgAN) is due to a primary defect in lymphokine regulation. In addition, we reasoned that such changes in lymphokine production might be, at least partially, genetically determined. To assess the extent of lymphocyte abnormalities, we investigated the profile of cytokine production from peripheral blood mononuclear cells (PBMC) in 34IgAN patients and 44 of their first degree relatives, 10 of whom had persistent microhaematuria. Compared with healthy volunteers (n=34), PBMC from patients showed increased IL-2 production both spontaneously or after phytohaemagglutinin (PHA) (20 μ/ml) stimulation, whereas IL-4 and interferon-gamma (IFN-γ) production were significantly higher only after stimulation. Microhaematuric relatives had a similar pattern of cytokine production, whereas non-microhaematuric relatives showed no significant difference versus normals. The altered pattern of cytokine production appeared to be quite specific to IgAN patients and their microhaematuric relatives, because patients with other forms of primary glomerulonephritis (n= 17) did not differ from normal individuals. Patients and relatives that hyperproduced IL-4 were also hyperproducers of IL-2. No such congruence was seen in any other group or with any other pairing of cytokines. We propose that a subpopulation of IgAN patients bear lymphocytes intrinsically hyper responsive. Among those individuals such hyperresponsiveness may be causally related to the pathogenesis and/or character of IgAN.