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Asymptomatic circulating T-cell clone cause renal polymorphic inflammatory fibrosis

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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.

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Authors and Affiliations

  1. Département de Néphrologie et Transplantation d’organes et Centre de référence des maladies rénales rares, CHU Rangueil, Toulouse, France

    David Ribes, Hélène EL Hachem, Dominique Chauveau & Stanislas Faguer

  2. Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France

    Audrey Casemayou, Joost P. Schanstra, Dominique Chauveau, Jean-Loup Bascands & Stanislas Faguer

  3. Université Paul Sabatier, Toulouse III, Toulouse, France

    Audrey Casemayou, Hélène EL Hachem, Céline Guilbeau-Frugier, Joost P. Schanstra, Dominique Chauveau, Jean-Loup Bascands & Stanislas Faguer

  4. Service d’Anatomo-pathologie, Institut Universitaire du Cancer de Toulouse, Oncopole, Toulouse, France

    Camille Laurent & Céline Guilbeau-Frugier

  5. Laboratoire d’Hématologie-Immunophénotypage et Hématologie Cellulaire, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France

    François Vergez

  6. Service d’Hématologie, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France

    Suzanne Tavitian & Loïc Ysebaert

  7. DéTROI - Inserm U1188 - Université de La Réunion Diabète athérothrombose Thérapies Réunion Océan Indien, Toulouse, France

    Jean-Loup Bascands

Authors
  1. David Ribes
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  2. Audrey Casemayou
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  3. Hélène EL Hachem
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  4. Camille Laurent
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  5. Céline Guilbeau-Frugier
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  6. François Vergez
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  7. Suzanne Tavitian
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  8. Joost P. Schanstra
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  9. Dominique Chauveau
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  10. Jean-Loup Bascands
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  11. Loïc Ysebaert
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  12. Stanislas Faguer
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Corresponding author

Correspondence to Stanislas Faguer.

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Conflict of interest

The authors declare that they have no conflicts of interests (financial or non financial).

Ethical statement

All procedures were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by our institutional ethical committee (collection NEPHROGENE No. DC-2011-1388, Comité de Protection des Personnes Sud-Ouest et Outremer II, Toulouse, France). For healthy donors (n = 2), peripheral blood mononuclear cells (PBMCs) were isolated from buffy coats obtained through the Etablissement Français du Sang (EFS Midi-Pyrénées, Purpan University Hospital, Toulouse, France). Blood samples were collected and processed after obtaining written informed consent from each donor and approval for this study by the local ethics committee (Comité de Protection des Personnes Sud-Ouest et Outremer II).

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Ribes, D., Casemayou, A., EL Hachem, H. et al. Asymptomatic circulating T-cell clone cause renal polymorphic inflammatory fibrosis. Clin Exp Nephrol 21, 781–786 (2017). https://doi.org/10.1007/s10157-016-1373-6

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  • DOI: https://doi.org/10.1007/s10157-016-1373-6

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