title: Asymptomatic circulating T-cell clone cause renal polymorphic inflammatory fibrosis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Département de Néphrologie et Transplantation d'organes et Centre de référence des maladies rénales rares, CHU Rangueil, Toulouse, France.
authors.forename: David
authors.initials: D
authors.lastname: Ribes
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France.|Université Paul Sabatier, Toulouse III, Toulouse, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Casemayou
authors.affiliation: Département de Néphrologie et Transplantation d'organes et Centre de référence des maladies rénales rares, CHU Rangueil, Toulouse, France.|Université Paul Sabatier, Toulouse III, Toulouse, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: El Hachem
authors.affiliation: Service d'Anatomo-pathologie, Institut Universitaire du Cancer de Toulouse, Oncopole, Toulouse, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Laurent
authors.affiliation: Université Paul Sabatier, Toulouse III, Toulouse, France.|Service d'Anatomo-pathologie, Institut Universitaire du Cancer de Toulouse, Oncopole, Toulouse, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Guilbeau-Frugier
authors.affiliation: Laboratoire d'Hématologie-Immunophénotypage et Hématologie Cellulaire, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.
authors.forename: François
authors.initials: F
authors.lastname: Vergez
authors.affiliation: Service d'Hématologie, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Tavitian
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France.|Université Paul Sabatier, Toulouse III, Toulouse, France.
authors.forename: Joost P
authors.initials: JP
authors.lastname: Schanstra
authors.affiliation: Département de Néphrologie et Transplantation d'organes et Centre de référence des maladies rénales rares, CHU Rangueil, Toulouse, France.|Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France.|Université Paul Sabatier, Toulouse III, Toulouse, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Chauveau
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France.|Université Paul Sabatier, Toulouse III, Toulouse, France.|DéTROI - Inserm U1188 - Université de La Réunion Diabète athérothrombose Thérapies Réunion Océan Indien, Toulouse, France.
authors.forename: Jean-Loup
authors.initials: JL
authors.lastname: Bascands
authors.affiliation: Service d'Hématologie, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Ysebaert
authors.affiliation: Département de Néphrologie et Transplantation d'organes et Centre de référence des maladies rénales rares, CHU Rangueil, Toulouse, France. faguer.s@chu-toulouse.fr.|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.|Université Paul Sabatier, Toulouse III, Toulouse, France. faguer.s@chu-toulouse.fr.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Faguer
mesh_terms: D000368:Aged; D001706:Biopsy; D002460:Cell Line; D002999:Clone Cells; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D005455:Fluorescent Antibody Technique; D015329:Gene Rearrangement, T-Lymphocyte; D019672:Genes, T-Cell Receptor; D006801:Humans; D016130:Immunophenotyping; D007668:Kidney / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D054066:Leukemia, Large Granular Lymphocytic / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D016328:NF-kappa B / Q000378:metabolism; D009395:Nephritis, Interstitial / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D016328:NF-kappa B
keywords: Biomed-2; Interstitial nephritis; Large granular lymphocytic leukemia; Renal fibrosis; T-cell clone