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Tissue deposits of IgA-binding streptococcal M proteins in IgA nephropathy and Henoch-Schonlein purpura.

Schmitt, Roland LU ; Carlsson, Fredric LU ; Mörgelin, Matthias LU ; Tati, Ramesh LU ; Lindahl, Gunnar LU and Karpman, Diana LU (2010) In American Journal of Pathology 176(2). p.608-618
Abstract
IgA nephropathy (IgAN) and Henoch-Schönlein purpura (HSP) are diseases characterized by IgA deposits in the kidney and/or skin. Both may arise after upper respiratory tract infections, but the pathogenic mechanisms governing these diseases remain unclear. Patients with IgAN (n = 16) and HSP (n = 17) were included in this study aimed at examining whether IgA-binding M proteins of group A streptococci could be involved. As M proteins vary in sequence, the study focused on the IgA-binding-region (IgA-BR) of three different M proteins: M4, M22, and M60. Renal tissue from IgAN and HSP patients and skin from HSP patients were examined for deposits of streptococcal IgA-BR by immunohistochemistry and electron microscopy using specific antibodies,... (More)
IgA nephropathy (IgAN) and Henoch-Schönlein purpura (HSP) are diseases characterized by IgA deposits in the kidney and/or skin. Both may arise after upper respiratory tract infections, but the pathogenic mechanisms governing these diseases remain unclear. Patients with IgAN (n = 16) and HSP (n = 17) were included in this study aimed at examining whether IgA-binding M proteins of group A streptococci could be involved. As M proteins vary in sequence, the study focused on the IgA-binding-region (IgA-BR) of three different M proteins: M4, M22, and M60. Renal tissue from IgAN and HSP patients and skin from HSP patients were examined for deposits of streptococcal IgA-BR by immunohistochemistry and electron microscopy using specific antibodies, and a skin sample from a HSP patient was examined by mass spectrometry. IgA-BR deposits were detected in 10/16 IgAN kidneys and 7/13 HSP kidneys. Electron microscopy demonstrated deposits of IgA-BRs in the mesangial matrix and glomerular basement membrane, which colocalized with IgA. Skin samples exhibited IgA-BR deposits in 4/5 biopsies, a result confirmed by mass spectrometry in one patient. IgA-BR deposits were not detected in normal kidney and skin samples. Taken together, these results demonstrate IgA-BR from streptococcal M proteins in patient tissues. IgA-BR, would on gaining access to the circulation, encounter circulatory IgA and form a complex with IgA-Fc that could deposit in tissues and contribute to the pathogenesis of IgAN and HSP. (Less)
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Contribution to journal
publication status
published
subject
in
American Journal of Pathology
volume
176
issue
2
pages
608 - 618
publisher
American Society for Investigative Pathology
external identifiers
  • wos:000274111400012
  • pmid:20056836
  • scopus:76149095207
ISSN
1525-2191
DOI
10.2353/ajpath.2010.090428
language
English
LU publication?
yes
id
dcb350d8-6c99-4bce-bcf2-6efeaac95888 (old id 1541336)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20056836?dopt=Abstract
date added to LUP
2010-02-02 12:03:57
date last changed
2018-07-01 04:23:35
@article{dcb350d8-6c99-4bce-bcf2-6efeaac95888,
  abstract     = {IgA nephropathy (IgAN) and Henoch-Schönlein purpura (HSP) are diseases characterized by IgA deposits in the kidney and/or skin. Both may arise after upper respiratory tract infections, but the pathogenic mechanisms governing these diseases remain unclear. Patients with IgAN (n = 16) and HSP (n = 17) were included in this study aimed at examining whether IgA-binding M proteins of group A streptococci could be involved. As M proteins vary in sequence, the study focused on the IgA-binding-region (IgA-BR) of three different M proteins: M4, M22, and M60. Renal tissue from IgAN and HSP patients and skin from HSP patients were examined for deposits of streptococcal IgA-BR by immunohistochemistry and electron microscopy using specific antibodies, and a skin sample from a HSP patient was examined by mass spectrometry. IgA-BR deposits were detected in 10/16 IgAN kidneys and 7/13 HSP kidneys. Electron microscopy demonstrated deposits of IgA-BRs in the mesangial matrix and glomerular basement membrane, which colocalized with IgA. Skin samples exhibited IgA-BR deposits in 4/5 biopsies, a result confirmed by mass spectrometry in one patient. IgA-BR deposits were not detected in normal kidney and skin samples. Taken together, these results demonstrate IgA-BR from streptococcal M proteins in patient tissues. IgA-BR, would on gaining access to the circulation, encounter circulatory IgA and form a complex with IgA-Fc that could deposit in tissues and contribute to the pathogenesis of IgAN and HSP.},
  author       = {Schmitt, Roland and Carlsson, Fredric and Mörgelin, Matthias and Tati, Ramesh and Lindahl, Gunnar and Karpman, Diana},
  issn         = {1525-2191},
  language     = {eng},
  number       = {2},
  pages        = {608--618},
  publisher    = {American Society for Investigative Pathology},
  series       = {American Journal of Pathology},
  title        = {Tissue deposits of IgA-binding streptococcal M proteins in IgA nephropathy and Henoch-Schonlein purpura.},
  url          = {http://dx.doi.org/10.2353/ajpath.2010.090428},
  volume       = {176},
  year         = {2010},
}