Diminished synthesis of immunoglobulin by peripheral lymphocytes of patients with idiopathic membranous glomerulonephropathy.

Ooi, Boon Seng; Ooi, Yuet M.; Hsu, Angela; Hurtubise, Paul E.

doi:10.1172/jci109729

Cited by 48 publications

(19 citation statements)

References 28 publications

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“…However, since IgG subclasses appear in the urine in proportions similar to their relative concentrations in the serum (15), the possibility of selective urinary loss of particular IgG subclasses can be excluded. Furthermore, the report that the synthesis of IgG by pokeweed mitogen-stimulated peripheral blood lymphocytes is diminished in MNand MCNSin vitro (16,17) supports the idea that the variable levels of serum IgG subclasses in patients with LNor MNare determined by the difference in the production rate of each IgG subclass. In this context, the increase in the %IgG4in association with a slightly elevated serum IgG4 concentration, while the total serum IgG level is decreased in patients with MN,is significant.…”

Section: Discussionmentioning

confidence: 90%

“…In addition, the depression of the serum IgG levels in patients with nephrotic syndrome due to a primary glomerulopathy, such as minimal change nephrotic syndrome (MCNS) and MNmay be considered (15)(16)(17). However, since IgG subclasses appear in the urine in proportions similar to their relative concentrations in the serum (15), the possibility of selective urinary loss of particular IgG subclasses can be excluded.…”

Section: Discussionmentioning

confidence: 99%

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Glomerular and Serum IgG Subclasses in Diffuse Proliferative Lupus Nephritis, Membranous Lupus Nephritis, and Idiopathic Membranous Nephropathy.

et al. 2002

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Objective To determine whether a different renal histopathology is associated with the characteristic IgG subclass distribution, and whether a distinct IgG subclass distribution is involved in a unique immunopathological expression, we compared the distributions of glomerular and serum IgG subclasses in diffuse proliferative lupus nephritis (DPLN), membranous LN (MLN), and idiopathic membranous nephropathy (MN).Patients and Methods The glomerular IgG subclass distributions in patients with DPLN(n=7), MLN(n=10) or MN(n=16) were assessed by direct immunofluorescence microscopy. Serum levels of each IgG subclass were quantitated by ELISA in DPLN, MLN, and MN patients, and in normal human sera (NHS) (n=14).Results IgGl, IgG2, IgG3, and, to a lesser degree, IgG4 were similarly present in glomerular deposits in both DPLN and MLN.In contrast, IgG4 was the predominant glomerular IgG subclass in MN. Regarding the serum IgG subclasses, the meanIgG subclass concentrations and the mean proportion of each IgG subclass to the total IgG (%IgG subclass) in DPLNand MLNwere not significantly different from those in NHS,except for the increased %IgGl in MLN.In MN,the mean %IgG4was selectively increased (p<0.01 vs NHS)in association with a slightly elevated IgG4 concentration; however, the meanconcentrations of other IgG subclasses were significantly decreased (p<0.01 vs NHS), and the %IgG subclasses were not significantly different from those in NHS. Conclusions The results indicate that the IgG subclass distribution is not associated with the different renal histopathologies of DPLNand MLN.This study also shows the selective significance of IgG4 in MN,but not in MLN,another form of membranous glomerulopathy. (Internal Medicine 41 : 936-942, 2002)

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Glomerular and Serum IgG Subclasses in Diffuse Proliferative Lupus Nephritis, Membranous Lupus Nephritis, and Idiopathic Membranous Nephropathy.

et al. 2002

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“…In addition, some reports have described impaired cell-mediated immunity, which seems to involve active accentuation of suppressor cells, in patients with idiopathic membranous nephropathy [2, 3, 4, 5, 6, 7, 8, 9]. Actually, as regards the cytokine production of stimulated lymphocytes, the decreased IL-2 production in idiopathic membranous nephropathy was previously reported [33], and in the present study, the percentages of IL-2-producing helper T cells from patients with idiopathic membranous nephropathy were significantly lower than those from normal individuals.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, IL-10 also inhibits class II major histocompatibility complex expression of antigen-presenting cells (APC) [37]and blocks APC-dependent T-cell proliferation [38]. The increase of IL-10-producing helper T cells and the decrease of IL-2-producing helper T cells in this disease might be strongly associated with impaired cell-mediated immunity, which seems to involve the active accentuation of suppressor cells [2, 3, 4, 5, 6, 7, 8, 9]. …”

Section: Discussionmentioning

confidence: 99%

“…Investigations of circulating peripheral blood mononuclear cells (PBMCs) obtained from patients with idiopathic membranous nephropathy have reported an overactive monocyte suppressor cell population [2], an increased helper-inducer T (OKT4+ or Leu3+)/suppressor-cytotoxic T (OKT8+ or Leu2+) cell ratio [3, 4], decreased suppressor T (Leu2a+Leu15+) cells, and increased suppressor-inducer T (Leu3a+Leu8+) cells [5]. Moreover, stimulated PBMCs analysis of patients with idiopathic membranous nephropathy has revealed decreased productions of IgG and IgM [6], alterations of concanavalin A (Con A)-induced suppressor cell activity [7, 8], and Con A-inducible suppression of in vitro immunoglobulin synthesis [9]. …”

Section: Introductionmentioning

confidence: 99%

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Predominance of Type-2 Immune Response in Idiopathic Membranous Nephropathy

Hirayama

Ebihara²,

Yamamoto³

et al. 2002

Nephron

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Background: The Th1/Th2 paradigm is proving increasingly useful in the understanding of infectious diseases and many autoimmune diseases. Th1 cells predominantly produce interleukin-2 (IL-2) and interferon-γ (IFN-γ) and are instrumental in initiating delayed-type hypersensitivity and activating macrophages. Th2 cells secrete other cytokines, such as IL-4, IL-5, IL-10 and IL-13 that trigger B-cell activation and immunoglobulin synthesis. It has been shown that in patients with membranous nephropathy, there may be a predominance of Th2, because of the presence of IgG, particularly IgG4, which belongs to a subclass of the type-2 immune response, and complement deposits in glomeruli. In this study, we investigated the immunoresponse of helper T cells, i.e. Th predominance in patients with idiopathic membranous nephropathy. Methods: We used flow cytometry to assess the levels of circulating Th cells in patients with idiopathic membranous nephropathy (n = 8) and in normal individuals (n = 23) based on the expression of intracellular type-1 and type-2 cytokines. Because the production of each of these cytokines has a specific time course, we observed the cytokine synthesis at 3, 6, 9 and 12 h after stimulation. Results: The percentages of IL-2+/CD4+ cells from patients with idiopathic membranous nephropathy were significantly lower than those from normal individuals at 6, 9 and 12 h, with the difference becoming more significant over time. IFN-γ+/CD4+ cells and IL-4+/CD4+ cells were not significantly different between the two groups. In patients with idiopathic membranous nephropathy, the percentages of IL-10+/CD4+ cells were significantly higher than those in normal individuals at each point in time. Conclusion: Increased IL-10-producing Th cells may lead to suppression of delayed-type hypersensitivity and activate suppressor cells and IgG4 synthesis, resulting in idiopathic membranous nephropathy.

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The Pathophysiological Consequences of Heavy Proteinuria

Glassock

1985

Proteinuria

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Diminished synthesis of immunoglobulin by peripheral lymphocytes of patients with idiopathic membranous glomerulonephropathy.

Cited by 48 publications

References 28 publications

Glomerular and Serum IgG Subclasses in Diffuse Proliferative Lupus Nephritis, Membranous Lupus Nephritis, and Idiopathic Membranous Nephropathy.

Glomerular and Serum IgG Subclasses in Diffuse Proliferative Lupus Nephritis, Membranous Lupus Nephritis, and Idiopathic Membranous Nephropathy.

Predominance of Type-2 Immune Response in Idiopathic Membranous Nephropathy

The Pathophysiological Consequences of Heavy Proteinuria

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