Changes in CD73, CD39 and CD26 expression on T-lymphocytes of ANCA-associated vasculitis patients suggest impairment in adenosine generation and turn-over

Extracellular adenosine, generated via the concerted action of CD39 and CD73, contributes to T-cell differentiation and function. Adenosine concentrations are furthermore influenced by adenosine deaminase binding protein CD26. Because aberrant T-cell phenotypes had been reported in anti-neutrophil c...

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Main Authors: Kling, Simon Lovis (Author) , Benck, Urs Tobias (Author) , Breedijk, Annette (Author) , Leikeim, Lisa (Author) , Porubský, Štefan (Author) , Krämer, Bernhard (Author) , Yard, Benito A. (Author) , Kälsch, Anna-Isabelle (Author)
Format: Article (Journal)
Language:English
Published: 15 September 2017
In: Scientific reports
Year: 2017, Volume: 7
ISSN:2045-2322
DOI:10.1038/s41598-017-12011-4
Online Access:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1038/s41598-017-12011-4
Verlag, kostenfrei, Volltext: http://www.nature.com/articles/s41598-017-12011-4
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Author Notes:Lovis Kling, Urs Benck, Annette Breedijk, Lisa Leikeim, Marianne Heitzmann, Stefan Porubsky, Bernhard K. Krämer, Benito A. Yard and Anna-Isabelle Kälsch
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Summary:Extracellular adenosine, generated via the concerted action of CD39 and CD73, contributes to T-cell differentiation and function. Adenosine concentrations are furthermore influenced by adenosine deaminase binding protein CD26. Because aberrant T-cell phenotypes had been reported in anti-neutrophil cytoplasmic auto-antibody (ANCA)-associated vasculitis (AAV) patients, an impaired expression of these molecules on T-cells of AAV patients was hypothesized in the present study. While in AAV patients (n = 29) CD26 was increased on CD4+ lymphocytes, CD39 and CD73 were generally reduced on patients’ T-cells. In CD4+ cells significant differences in CD73 expression were confined to memory CD45RA- cells, while in CD4- lymphocytes differences were significant in both naïve CD45RA+ and memory CD45RA- cells. The percentage of CD4-CD73+ cells correlated with micro-RNA (miR)−31 expression, a putative regulator of factor inhibiting hypoxia-inducible factor 1 alpha (FIH-1), inversely with serum C-reactive protein (CRP) and positively with estimated glomerular filtration rate (eGFR). No correlation with disease activity, duration, and ANCA profile was found. It remains to be assessed if a decreased CD73 and CD39 expression underlies functional impairment of lymphocytes in AAV patients. Likewise, the relations between frequencies of CD4-CD73+ cells and serum CRP or eGFR require further functional elucidation.
Item Description:Gesehen am 13.08.2018
Physical Description:Online Resource
ISSN:2045-2322
DOI:10.1038/s41598-017-12011-4