Tissue deposits of IgA-binding streptococcal M proteins in IgA nephropathy and Henoch-Schonlein purpura.
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.
Schmitt
Roland
R
Department of Pediatrics, Clinical Sciences Lund, Lund University, 22185 Lund, Sweden.
Carlsson
Fredric
F
Mörgelin
Matthias
M
Tati
Ramesh
R
Lindahl
Gunnar
G
Karpman
Diana
D
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D001706:Biopsy; D002352:Carrier Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005922:Glomerulonephritis, IGA / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D011695:IgA Vasculitis / Q000378:metabolism* / Q000473:pathology; D007070:Immunoglobulin A / Q000378:metabolism*; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D011234:Precipitins / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding; D012867:Skin / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D055815:Young Adult
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D007070:Immunoglobulin A; D011234:Precipitins; C014689:streptococcal M protein