Immunopathological features of palatine tonsil characteristic of IgA nephropathy: IgA1 localization in follicular dendritic cells

Abstract

SUMMARY IgA nephropathy (IgAN) is generally thought to be mediated by the glomerular deposition of circulating immune complexes containing IgA as the major antibody component. Upper respiratory infections and tonsillitis often precede IgAN. and in some cases tonsillectomy is affective for the (treatment of IgAN. Thus, the tonsil seems to be a unique organ causing initial and/or progressive events to generate nephritogenic immune complexes in IgAN. in this study we focused on the analysis of immunopathological features of the palatine tonsil characteristic of IgAN patients by using an immunohistochemical technique. The IgAl subclass was demonstrated in follicular dendritic cells (FDC) of the tonsil of IgAN patients, but not in FDC of non‐IgAN controls. On the other hand, IgA2, IgG, IgM and C3 did not show any differences in distribution between the two groups. Moreover, the expression of decay‐accelerating factor (DAF), an inhibitor of homologous complement activation, and transforming growth factor‐beta I (TGF‐/β1). an inducer of antibody‐producing ceils to IgA class switching, in FDC and interdigitating dendritic cells of the tonsil, respectively, which was also clarified in this study for the first time, was found to be identically distributed in the two groups. These findings may support the idea that IgA1. possibly in an immune complex form, is trapped by FDC and plays an important role in the persistent activation of particular B cell repertoires responsible for ihe onset and/or progression of IgAN.

Increased dimeric IgA-producing B cells in tonsils in IgA nephropathy determined byin situhybridization for J chain mRNA

“…v\e have previously reported reduction in IgA allinity to specific aniigen in IgAN [22]. Furthermore, abnormal igAl germinal centre staining has been recently reported [23]. Further study of this micro-anatomical siie is therefore warranted.…”

Immunobiology of the Tonsils and Adenoids

“…Huang et al (2010) found that their raised number of IgA + J-chain + PCs was accompanied by a decreased tonsillar number of CD4 + CD25 + putative Treg cells. Kusakari et al (1994) reported that the IgA1 subclass is present on tonsillar FDCs in such patients but not in nonIgA nephropathy controls. However, IgA2, IgG, IgM, and C3 did not show any differences in distribution between the two groups.…”

Pathological Role of Tonsillar B Cells in IgA Nephropathy

“…Furthermore, mucosal vaccination results in impaired mucosal IgA responses in IgAN whereas systemic antigen challenge results in increased titers of circulating pIgA1 antibodies with normal levels in mucosal secretions [ 28 , 29 ]. In addition, not only IgA + cells but also polymeric IgA are increasingly produced in the mucosa of IgAN patients [ 30 – 32 ]. On the other hand, there is a report demonstrating that there is a reduction in polymeric IgA producing cells in duodenum [ 33 ].…”