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Clin Exp Nephrol. 2017 Oct;21(5):781-786. doi: 10.1007/s10157-016-1373-6. Epub 2016 Dec 26.

Asymptomatic circulating T-cell clone cause renal polymorphic inflammatory fibrosis.

Author information

1
Département de Néphrologie et Transplantation d'organes et Centre de référence des maladies rénales rares, CHU Rangueil, Toulouse, France.
2
Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France.
3
Université Paul Sabatier, Toulouse III, Toulouse, France.
4
Service d'Anatomo-pathologie, Institut Universitaire du Cancer de Toulouse, Oncopole, Toulouse, France.
5
Laboratoire d'Hématologie-Immunophénotypage et Hématologie Cellulaire, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.
6
Service d'Hématologie, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.
7
DéTROI - Inserm U1188 - Université de La Réunion Diabète athérothrombose Thérapies Réunion Océan Indien, Toulouse, France.
8
Département de Néphrologie et Transplantation d'organes et Centre de référence des maladies rénales rares, CHU Rangueil, Toulouse, France. faguer.s@chu-toulouse.fr.
9
Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France. faguer.s@chu-toulouse.fr.
10
Université Paul Sabatier, Toulouse III, Toulouse, France. faguer.s@chu-toulouse.fr.

Abstract

BACKGROUND:

Renal complications of non-Hodgkin lymphoma encompass a wide spectrum of monoclonal Ig-related pathologies. Clonal circulating T cells can also be associated with non-renal autoimmune disorders induced by overproduction of specific patterns of cytokines or unbalanced lymphocytes sub-populations.

METHODS:

Immunophenotyping of circulating T cells and TCR gene restriction analysis using Biomed-2 protocol. NF-κB staining and mRNA quantification of inflammatory genes in HK-2 epithelial renal cells exposed to supernatants of peripheral blood mononuclear cells with clonal T-cell population.

RESULTS:

Here, we could identify a persistent clonal T-cell population, only characterized by in-depth immunophenotyping of circulating lymphocytes and using multiplex PCR analysis of TCR gene rearrangements, in two patients with polymorphic inflammatory renal fibrosis of unknown origin. Using an in vitro approach, we could demonstrate that peripheral blood mononuclear cells including the clonal population can trigger a phenotype switch of epithelial renal cells from a quiescent state to a pro-inflammatory state characterized by NF-κB nuclear translocation and overexpression of inflammatory cytokine or chemokine.

CONCLUSION:

These preliminary data suggest that circulating T-cell clones may directly activate epithelial renal cells or promote a T-/B-cell population with autoimmune reactive properties against kidney cells, which, in the absence of overt renal lymphoma infiltration, lead to the subsequent inflammatory renal fibrotic phenotype.

KEYWORDS:

Biomed-2; Interstitial nephritis; Large granular lymphocytic leukemia; Renal fibrosis; T-cell clone

PMID:
28018996
DOI:
10.1007/s10157-016-1373-6
[Indexed for MEDLINE]

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