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IgM contributes to glomerular injury in FSGS


Strassheim, D.; Renner, B. : Panzer, S.; Fuquay, R.; Kulik, L.; Galešić Ljubanović, Danica; Holers, V.M.; Thurman, J.M.
IgM contributes to glomerular injury in FSGS // Journal of the American Society of Nephrology, 24 (2013), 3; 393-406 doi:10.1681/ASN.2012020187 (međunarodna recenzija, članak, znanstveni)


Naslov
IgM contributes to glomerular injury in FSGS

Autori
Strassheim, D. ; Renner, B. : Panzer, S. ; Fuquay, R. ; Kulik, L. ; Galešić Ljubanović, Danica ; Holers, V.M. ; Thurman, J.M.

Izvornik
Journal of the American Society of Nephrology (1046-6673) 24 (2013), 3; 393-406

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
FSGS; glomerular injury; IgM

Sažetak
Glomerular IgM and C3 deposits frequently accompany idiopathic FSGS and secondary glomerulosclerosis, but it is unknown whether IgM activates complement, possibly contributing to the pathogenesis of these diseases. We hypothesized that IgM natural antibody binds to neoepitopes exposed in the glomerulus after nonimmune insults, triggering activation of the complement system and further injury. We examined the effects of depleting B cells, using three different strategies, on adriamycin-induced glomerulosclerosis. First, we treated wild-type mice with an anti-murine CD20 antibody, which depletes B cells, before disease induction. Second, we evaluated adriamycin-induced glomerulosclerosis in Jh mice, a strain that lacks mature B cells. Third, we locally depleted peritoneal B cells via hypotonic shock before disease induction. All three strategies reduced deposition of IgM in the glomerulus after administration of adriamycin and attenuated the development of albuminuria. Furthermore, we found that glomerular IgM and C3 were detectable in a subset of patients with FSGS ; C3 was present as an activation fragment and colocalized with glomerular IgM, suggesting that glomerular IgM may have bound a cognate ligand. Taken together, these results suggest that IgM activates the complement system within the glomerulus in an animal model of glomerulosclerosis. Strategies that reduce IgM natural antibody or that prevent complement activation may slow the progression of glomerulosclerosis.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti



POVEZANOST RADA


Projekt / tema
198-0000000-3355 - Značaj morfoloških čimbenika u dijagnostici, terapiji i prognozi FSGS (Danica Galešić-Ljubanović, )

Ustanove
Klinička bolnica "Dubrava"

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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