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10.4049/jimmunol.1302249

http://scihub22266oqcxt.onion/10.4049/jimmunol.1302249
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C4065838!4065838!24850720
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suck abstract from ncbi


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pmid24850720      J+Immunol 2014 ; 193 (1): 317-26
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  • The combined role of galactose-deficient IgA1and 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 PMID24850720show ga
  • IgA nephropathy 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 co-localize with IgA in mesangial immune deposits in patients with IgA nephropathy. In the current 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. Co-stimulation of human mesangial cells with M4 and galactose-deficient polymeric IgA1 resulted in a significant increase in IL-6 secretion compared to each stimulant alone. Galactose-deficient polymeric IgA1 alone, but not M4, induced C3 secretion from the cells and co-stimulation enhanced this effect. In addition, co-stimulation enhanced mesangial cell proliferation compared to 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 pro-inflammatory responses and proliferation of human mesangial cells. Thus, tissue deposition of streptococcal IgA-binding M proteins may contribute to the pathogenesis of IgA nephropathy.
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