当前位置： SCI文献检索 > CLINICAL AND EXPERIMENTAL IMMUNOLOGY期刊下所有文献 > Studies of the molecular basis of IgA production, subclass regulation and class-switch recombination in IgA nephropathy patients.

Studies of the molecular basis of IgA production, subclass regulation and class-switch recombination in IgA nephropathy patients.

Abstract：

:IgA nephropathy (IgAN), the most common form of glomerulonephritis, is characterized by normal to elevated levels of serum IgA. In order to understand the molecular mechanism(s) involved in the production of IgA in IgAN, peripheral blood mononuclear cells (PBMC) from these patients were analysed in this study. IL-10, transforming growth factor-beta 1 (TGF-beta 1) and CD40 have previously been shown to be involved in IgA production. We show here that CD40L expression was increased three-fold in these patients. However, expression of TGF-beta 1 in serum levels was comparable to controls. In vitro stimulation of PBMC with a polyclonal activator resulted in a three-fold increase in synthesis of both IgA subclasses, with a preference for IgA1 RNA. In situ hybridization studies also showed a three-fold increase in the numbers of IgA1- and IgA2-producing cells, but the subclass distribution was similar to the controls. Furthermore, using the nested primer polymerase chain reaction (PCR) for amplifying switch (S mu/S alpha) breakpoints we could demonstrate that in unstimulated PBMC the switch frequency did not differ from that of control donors. Sequence analysis of the amplified switch breakpoints and the I alpha regulatory region from patients showed no structural abnormality. Although we have previously demonstrated a correlation to in vivo germ-line RNA expression and class switching, no I alpha transcripts were detected in unstimulated PBMC from these patients. However, stimulation of PBMC with TGF-beta 1 resulted in I alpha production. Taken together, results from in vivo and in vitro studies suggest that increased cytokine production and hyperresponsiveness to polyclonal stimulation may play an important role in the increased synthesis of IgA. The preference for IgA1 is due to increased production of IgA1 per cell, and the absence of I alpha RNA indicates that additional defect(s) in immune regulation may play an important role in the pathogenesis of IgAN.

journal_name

Clin Exp Immunol

journal_title

Clinical and experimental immunology

authors

Baskin B,Pettersson E,Rekola S,Smith CI,Islam KB

doi

10.1046/j.1365-2249.1996.d01-859.x

subject

Has Abstract

pub_date

1996-12-01 00:00:00

pages

509-17

issue

eissn

0009-9104

issn

1365-2249

journal_volume

106

pub_type

杂志文章

在线工具

Studies of the molecular basis of IgA production, subclass regulation and class-switch recombination in IgA nephropathy patients.