Document Detail


Interstitial inflammation in Alport syndrome.
MedLine Citation:
PMID:  20004949     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Alport syndrome is a hereditary glomerular disease linked to structural abnormalities of collagen IV. In a mouse model of Alport syndrome, the interstitial lymphocyte influx was important for disease progression. CXCR3 is a chemokine receptor involved in lymphocyte recruitment to the kidney. We hypothesized that CXCR3-positive T cells might be involved in human Alport syndrome. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded biopsies from 17 patients with Alport syndrome, 10 with immunoglobulin A (IgA) nephropathy, and 11 healthy donor kidneys. We investigated the expression of the alpha5 chain of collagen IV to confirm the morphologic diagnosis, the chemokine receptor CXCR3 and CD3-positive T cells. Alport syndrome biopsies demonstrated a complete loss of the alpha5 chain of collagen IV from the glomerular basement membrane and the morphologic features consistent with Alport syndrome on electron microscopy. A prominent number of CXCR3-positive cells were found in the tubulointerstitium. Most of the CXCR3-positive cells were CD3-positive T cells, demonstrated by double-labeling in selected biopsies. The number of CXCR3-positive cells in kidneys with Alport syndrome correlated with serum creatinine (P < .05) and with morphologic features of a progressive disease (eg, interstitial fibrosis, glomerulosclerosis, and tubular atrophy). The severity of interstitial CXCR3-positive cell influx was similar in Alport syndrome as compared to immunoglobulin A nephropathy. The noninflammatory glomerular lesion of Alport syndrome is associated with prominent interstitial accumulation of CD3- and CXCR3-positive lymphocytes. The degree of infiltration correlated with renal function. We speculate that targeting T lymphocytes, for example, by CXCR3 blocking agents, might be a novel approach to inhibit disease progression in patients with Alport syndrome.
Authors:
Jan Jedlicka; Afschin Soleiman; Dan Draganovici; Jana Mandelbaum; Urs Ziegler; Heinz Regele; Rudolf P W?thrich; Oliver Gross; Hans-Joachim Anders; Stephan Segerer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-11
Journal Detail:
Title:  Human pathology     Volume:  41     ISSN:  1532-8392     ISO Abbreviation:  Hum. Pathol.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-15     Completed Date:  2010-03-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421547     Medline TA:  Hum Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  582-93     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Inc.
Affiliation:
Medizinische Poliklinik Campus Innenstadt, University of Munich, 80336 Munich, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Animals
Antigens, CD3 / metabolism
Child
Child, Preschool
Female
Humans
Male
Nephritis, Hereditary / immunology*,  pathology
Nephritis, Interstitial / immunology*,  pathology
Receptors, CXCR3 / metabolism
T-Lymphocytes / immunology,  metabolism
Young Adult
Chemical
Reg. No./Substance:
0/Antigens, CD3; 0/CXCR3 protein, human; 0/Receptors, CXCR3

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