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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Immunol
2014 ; 193
(1
): 317-26
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
The combined role of galactose-deficient IgA1 and streptococcal IgA-binding M
Protein in inducing IL-6 and C3 secretion from human mesangial cells:
implications for IgA nephropathy
#MMPMID24850720
Schmitt R
; Ståhl AL
; Olin AI
; Kristoffersson AC
; Rebetz J
; Novak J
; Lindahl G
; Karpman D
J Immunol
2014[Jul]; 193
(1
): 317-26
PMID24850720
show ga
IgA nephropathy (IgAN) is characterized by mesangial cell proliferation and
extracellular matrix expansion associated with immune deposits consisting of
galactose-deficient polymeric IgA1 and C3. We have previously shown that
IgA-binding regions of streptococcal M proteins colocalize with IgA in mesangial
immune deposits in patients with IgAN. In the present study, the IgA-binding M4
protein from group A Streptococcus was found to bind to galactose-deficient
polymeric IgA1 with higher affinity than to other forms of IgA1, as shown by
surface plasmon resonance and solid-phase immunoassay. The M4 protein was
demonstrated to bind to mesangial cells not via the IgA-binding region but rather
via the C-terminal region, as demonstrated by flow cytometry. IgA1 enhanced
binding of M4 to mesangial cells, but not vice versa. Costimulation of human
mesangial cells with M4 and galactose-deficient polymeric IgA1 resulted in a
significant increase in IL-6 secretion compared with each stimulant alone.
Galactose-deficient polymeric IgA1 alone, but not M4, induced C3 secretion from
the cells, and costimulation enhanced this effect. Additionally, costimulation
enhanced mesangial cell proliferation compared with each stimulant alone. These
results indicate that IgA-binding M4 protein binds preferentially to
galactose-deficient polymeric IgA1 and that these proteins together induce
excessive proinflammatory responses and proliferation of human mesangial cells.
Thus, tissue deposition of streptococcal IgA-binding M proteins may contribute to
the pathogenesis of IgAN.