Increase of CD23-Positive Cells in Peripheral Blood from Patients with IgA Nephropathy and Non-lgA Proliferative Glomerulonephritis

Yano, N.; Miyazaki, M.; Endoh, Masayuki; Kuramoto, Takao; Eguchi, Kazuhiko; Yagame, Mitsunori; Nomoto, Yasuo; Sakai, Hideaki

doi:10.1159/000186799

Cited by 22 publications

(10 citation statements)

References 18 publications

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“…These findings were absolutely IgAN specific, and serum IgE levels showed no positive correlations with serum activities of IL-4 or serum sCD23 levels in patients with PGN or normal controls (data not shown). We pre viously reported enhanced expression of surface CD23 on peripheral lymphocytes and elevated serum IgE levels in patients with IgAN [29]. These experimental results sug gested that IL-4 and sCD23 play regulatory roles in in vivo production of IgE in patients with IgAN.…”

Section: Discussionmentioning

confidence: 63%

Involvement of lnterleukin-4 and Soluble CD23 in Hypersynthesis of Immunoglobulins A and E in Patients with IgA Nephropathy

Yano

Endoh²,

Takemura³

et al. 1996

Nephron

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To determine the cytokines responsible for the increase in production of IgA in patients with IgA nephropathy (IgAN), the roles of interleukin-4 (IL-4) and soluble CD23 (sCD23) were examined. Peripheral blood mononuclear cells (PBMCs) and serum were obtained from 24 patients with IgAN and 14 patients with non-IgA proliferative glomerulonephritis. Twenty healthy adults served as controls. Concentrations of IgA and IgE in 10-day culture supernatants of PBMCs were measured by the sandwich ELISA method. Levels of sCD23 and activities of IL-4 in 4-day (96-hour) culture supernatants and serum were measured by ELISA and bioassay, respectively. Activities of IL-4 both in culture supernatants and serum were significantly elevated in patients with IgAN compared with controls (1.26 ± 0.53 vs. 0.68 ± 0.37 U/ml in culture supernatants, p < 0.05; 1.35 ± 1.34 vs. 0.89 ± 0.82 U/ml in serum, p < 0.05). Levels of sCD23 in IgAN patients’ serum were also significantly elevated (521.7 ± 514.9 vs. 173.0 ± 166.2 U/ml, p < 0.01). In vitro IgA and IgE synthesis were suppressed by anti-IL-4 monoclonal antibody (mAb) only when the antibody was added on the day when the culture was started (day 0). No suppression of IgA or IgE synthesis was observed when the antibody was added on day 4. IgE but not IgA synthesis was suppressed by anti-CD23 mAb when added on both days 0 and 4. Serum levels of IgE showed positive correlations with serum activities of IL-4 and with levels of serum sCD23. It is concluded that IL-4 and sCD23 might play decisive roles in in vitro and in vivo hyperproduction of IgA and IgE in patients with IgAN, and that sCD23 seemed to control IgE but not IgA synthesis through a unique pathway.

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Section: Discussionmentioning

confidence: 63%

Involvement of lnterleukin-4 and Soluble CD23 in Hypersynthesis of Immunoglobulins A and E in Patients with IgA Nephropathy

Yano

Endoh²,

Takemura³

et al. 1996

Nephron

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“…These findings suggest that in HIGA mice not only the class switching to sIgA+ cells, but also the production and/or secretion of IgA from these cells was accelerated. In human IgA nephropathy, abnormally activated B cell function in the production of IgA has been reported to be a background factor in a number of patients with elevated serum IgA levels [14, 15], although there was no evidence for increased numbers of circulating IgA-bearing B cells. The background factors that may influence the high concentrations of serum IgA and glomerular lesions that are common to both HIGA mice and IgA nephropathy patients should be investigated further.…”

Section: Discussionmentioning

confidence: 99%

Up-Regulated TGF-β mRNA Expression in Splenic T Cells of High IgA-Prone Mice: A Murine Model of IgA Nephropathy with Glomerulosclerosis

Oyama

Muso

Ono

et al. 2001

Nephron

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Background/Aims: Recently, we established a high serum IgA-prone inbred (HIGA) mouse strain as a murine model of spontaneous IgA nephropathy by selective mating of high serum IgA ddY mice, and found that they showed enhanced production of glomerular extracellular matrix components with increased expression of TGF-β mRNA and protein in the kidneys. In this study, we examined the roles of lymphocytes in the development of high serum IgA in this strain. Methods: We performed flow cytometric analyses of T and B cells in splenic mononuclear cells (SMNCs) from these mice using BALB/c mice as normal controls. We also compared serum TGF-β1 concentrations and TGF-β mRNA expression levels in the B-cell-depleted (T-cell-rich) fraction of SMNCs in these mice. Results: HIGA mice showed significantly fewer CD3-positive cells compared with BALB/c mice when young, but not when aged. The CD4/CD8 ratio of HIGA mice was lower than that of BALB/c mice, but this difference was not significant. Although the number of B220-positive cells did not vary significantly, the ratio of surface IgA-positive B cells was significantly increased in both young and adult HIGA mice. The B-cell-depleted SMNCs from HIGA mice exhibited higher levels of expression of TGF-β and TGF-β1 mRNA than controls from a young age, which were maintained throughout life, but there were no differences in PDGF, MCP-1 or bFGF expression between these two strains. In contrast to local mRNA expression, serum TGF-β1 concentration was decreased in HIGA mice compared with BALB/c controls. Conclusion: These findings suggest that the mating procedure performed to establish HIGA mice selected for a unique phenotype of local up-regulation of TGF-β production in the kidneys, as well as T cells that may contribute to both the early and consistently high serum IgA expression and enhanced production of renal extracellular matrix components in HIGA mice. Additionally, TGF-β1 may act locally, not systemically, in a paracrine or autocrine manner.

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“…Regarding the significance of lhe eytokine alterations revealed in patients, it is noteworthy that IL-4 and IFN-v are known loplay a key role in immunoglobulin class switehingf 12], and iL-4 and IFN-7 influence IgF and IgA synthesis from the PBMC of IgAN patients [30.31] and account for the increase in CD23* cells in IgAN patients [32].…”

Section: Discussionmentioning

confidence: 99%

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

Scivittaro

Gesualdo

Ranieri

et al. 1994

Clinical and Experimental Immunology

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SUMMARYWe hypothesized that the altered immunoglobulin synthesis and/or lymphocyte ("unciion apparent in patients with IgA nephropathy (IgAN) is due to a primary defeet in lymphokine regulation. In addition, we reasoned that such changes in lymphokine production might be, at least partially, genetically determined. To assess the extent ot'lymphocyte abnormalities, we investigated lhe profile of cytokine production from peripheral blood mononuclear cells (PBMC) in .14 IgAN piilicmsand44 of their first degree relatives, 10 of whom had persistent mierohaematuria. Compared wilh healthy volunteers (o = 34), PBMC from patients showed increased IL-2 production both spontaneously or after phytohaemagglutinin (PHA) (20 /ig/ml) stimulation, whereas lL-4 and interferon-gamma (IFN-y) production were significantly higher only after stimulation. Mierohaemaluric relatives liad a similar pattern of eytokine production, whereas non-microhaematuric relatives showed no significant diflerence 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 eytokines. 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.

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Increase of CD23-Positive Cells in Peripheral Blood from Patients with IgA Nephropathy and Non-lgA Proliferative Glomerulonephritis

Cited by 22 publications

References 18 publications

Involvement of lnterleukin-4 and Soluble CD23 in Hypersynthesis of Immunoglobulins A and E in Patients with IgA Nephropathy

Involvement of lnterleukin-4 and Soluble CD23 in Hypersynthesis of Immunoglobulins A and E in Patients with IgA Nephropathy

Up-Regulated TGF-β mRNA Expression in Splenic T Cells of High IgA-Prone Mice: A Murine Model of IgA Nephropathy with Glomerulosclerosis

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

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