IgA production and tonsillar focal infection in IgA nephropathy

J Clin Exp Hematop. 2012;52(3):161-70. doi: 10.3960/jslrt.52.161.

Abstract

IgA nephropathy (IgAN), the common primary glomerulonephritis, is a tonsillar focal infection characterized by the qualitative abnormality of IgA in circulation and IgA deposition in the renal mesangium. Mesangial deposition of IgA, which is composed predominantly of poorly galactosylated polymeric IgA1 (pIgA1), seems to be the initiating event in the pathogenesis of IgAN. The origin of poorly galactosylated IgA, however, remains unclear. Recent studies suggest that the mesangial polymeric IgA1 deposition could be derived from mucosally primed plasma cells. B cells may undergo IgA class switching to acquire the expression of IgA via T-cell-dependent or T-cell-independent pathways in mucosa-associated lymphoid tissue and then differentiate to IgA plasma cells or home in on systemic sites. Dendritic cells, including plasmacytoid dendritic cells and another type of antigen-retaining cell, follicular dendritic cells, have an irreplaceable role in IgA class-switch mechanisms by producing IgA-inducing signals. Furthermore, an increased number of pIgA1-secreting plasma cells in the bone marrow and tonsil, as well as increased IgA class switching, have been found in IgAN, providing a link between the mucosal immunity and IgAN. The favorable effect of tonsillectomy on patients with IgAN showed that tonsillar focal infection may be closely related to pIgA1 deposition in glomerular mesangium of patients with IgAN and at least a part of pIgA1 may originate from affected tonsils. Therefore, the indication for tonsillectomy should be considered in patients with IgA nephropathy, especially at a mild or early stage, to prevent future renal deterioration. In this paper, we focus on IgA class switching and the role of tonsils with focal infection in IgAN.

Publication types

  • Review

MeSH terms

  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Bone Marrow / immunology
  • Bone Marrow / pathology
  • Complement Activation
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Focal Infection / immunology*
  • Focal Infection / pathology
  • Glomerular Mesangium / immunology*
  • Glomerular Mesangium / pathology
  • Glomerulonephritis, IGA / immunology*
  • Glomerulonephritis, IGA / pathology
  • Glomerulonephritis, IGA / surgery
  • Humans
  • Immunity, Mucosal
  • Immunoglobulin A / biosynthesis
  • Immunoglobulin A / immunology*
  • Immunoglobulin Class Switching
  • Palatine Tonsil / immunology*
  • Palatine Tonsil / pathology
  • Palatine Tonsil / surgery
  • Plasma Cells / immunology
  • Plasma Cells / pathology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • Tonsillectomy

Substances

  • Immunoglobulin A