Document Detail


Activated innate immunity and the involvement of CX3CR1-fractalkine in promoting hematuria in patients with IgA nephropathy.
MedLine Citation:
PMID:  22572859     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
A hallmark of immunoglobulin A nephropathy (IgAN) is episodes of gross hematuria coinciding with mucosal infections that can represent the disease-triggering event. Here we performed a whole genomic screen of IgAN patients during gross hematuria to clarify the link between mucosal antigens and glomerular hematuria. Modulated genes showed a clear involvement of the intracellular interferon signaling, antigen-presenting pathway, and the immunoproteasome. The mRNA and protein level of the chemokine receptor characterizing cytotoxic effector lymphocytes, CX3CR1, was upregulated. In vitro antigenic stimulation of peripheral blood mononuclear cells from IgAN patients, healthy blood donors, and other nephropathies with microscopic hematuria showed that only in IgAN patients was CX3CR1 enhanced in a dose-dependent manner. A significantly higher amount of glomerular and urinary fractalkine, the only ligand of CX3CR1, was also found in IgAN patients with recurrent episodes of gross hematuria compared with other patients with microscopic or no hematuria. This suggests a predisposition for cytotoxic cell extravasation only in patients with recurrent gross hematuria. Thus, we found a defect in antigen handling in peripheral blood mononuclear cells of IgAN patients with a specific increase of CX3CR1. This constitutive upregulation of glomerular and urinary fractalkine suggests an involvement of the CX3CR1-fractalkine axis in the exacerbation of gross hematuria.Kidney International advance online publication, 9 May 2012; doi:10.1038/ki.2012.147.
Authors:
Sharon N Cox; Fabio Sallustio; Grazia Serino; Antonia Loverre; Francesco Pesce; Margherita Gigante; Gianluigi Zaza; Patrizia F Stifanelli; Nicola Ancona; Francesco P Schena
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-09
Journal Detail:
Title:  Kidney international     Volume:  -     ISSN:  1523-1755     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Emergency and Organ Transplantation, Nephrology Dialysis and Transplantation Unit, University of Bari, Bari, Italy.
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