Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 176, Issue 2, Pages 608-618Publisher
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2010.090428
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Funding
- Swedish Research Council [06X-14008, 06X-09490]
- Sven Jerring Foundation
- Fanny Ekdahl foundation
- Region SkAne
- Kristianstad Hogskola
- Samariten Foundation
- Foundations of GoIje and Lundstrbm
- Royal Physiographic Society in Lund
- Foundations of Kock and Osterlund
- Royal Swedish Academy of Sciences
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IgA nephropathy (IgAN) and Henoch-Schonlein 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. lgA-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. lgA-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. (Am J Pathol 2010, 176-608-618, DOI: 10.2353/ajpath.2010.090428)
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