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Hesse J, Siekierka-Harreis M, Steckel B, et al. Profound inhibition of CD73-dependent formation of anti-inflammatory adenosine in B cells of SLE patients. EBioMedicine. 2021;73:103616doi: 10.1016/j.ebiom.2021.103616.
Hesse, J., Siekierka-Harreis, M., Steckel, B., Alter, C., Schallehn, M., Honke, N., Schnieringer, M. L., Wippich, M., Braband, R., Schneider, M., Surowy, H., Wieczorek, D., Schrader, J., & Pongratz, G. (2021). Profound inhibition of CD73-dependent formation of anti-inflammatory adenosine in B cells of SLE patients. EBioMedicine, 73103616. https://doi.org/10.1016/j.ebiom.2021.103616
Hesse, Julia, et al. "Profound inhibition of CD73-dependent formation of anti-inflammatory adenosine in B cells of SLE patients." EBioMedicine vol. 73 (2021): 103616. doi: https://doi.org/10.1016/j.ebiom.2021.103616
Hesse J, Siekierka-Harreis M, Steckel B, Alter C, Schallehn M, Honke N, Schnieringer ML, Wippich M, Braband R, Schneider M, Surowy H, Wieczorek D, Schrader J, Pongratz G. Profound inhibition of CD73-dependent formation of anti-inflammatory adenosine in B cells of SLE patients. EBioMedicine. 2021 Nov;73:103616. doi: 10.1016/j.ebiom.2021.103616. Epub 2021 Oct 16. PMID: 34666225; PMCID: PMC8524755.
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EBioMedicine. 2021 Nov;73:103616. doi: 10.1016/j.ebiom.2021.103616. Epub 2021 Oct 16.

Profound inhibition of CD73-dependent formation of anti-inflammatory adenosine in B cells of SLE patients.

EBioMedicine

Julia Hesse, Magdalena Siekierka-Harreis, Bodo Steckel, Christina Alter, Merle Schallehn, Nadine Honke, Marie-Laure Schnieringer, Madita Wippich, Rebekka Braband, Matthias Schneider, Harald Surowy, Dagmar Wieczorek, Jürgen Schrader, Georg Pongratz

Affiliations

  1. Department of Molecular Cardiology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany.
  2. Policlinic of Rheumatology & Hiller Research Unit, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.
  3. Institute of Human Genetics, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany.
  4. Department of Molecular Cardiology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany. Electronic address: [email protected].
  5. Policlinic of Rheumatology & Hiller Research Unit, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany. Electronic address: [email protected].

PMID: 34666225 PMCID: PMC8524755 DOI: 10.1016/j.ebiom.2021.103616

Abstract

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that leads to a breakdown of tolerance to self-antigens resulting in inflammation and organ damage. The anti-inflammatory activity of CD73-derived adenosine is well documented, however, its role in SLE pathogenesis is unknown.

METHODS: Human peripheral blood immune cells were obtained from adult SLE patients (SLE) and healthy controls (HC). Expression and activity of purinergic ectoenzymes were assessed by qRT-PCR, flow cytometry and HPLC. Genes encoding purinergic ectoenzymes in SLE patients were analysed with targeted DNA sequencing.

FINDINGS: Among circulating immune cells (both in HC and SLE), CD73 was most highly expressed on B cells, which was mirrored by high enzymatic activity only in HC. CD73 protein molecular weight was unchanged in SLE, however, the enzymatic activity of CD73 on SLE B cells was almost fully abolished. Accordingly, AMP accumulated in cultured SLE B cells. A similar discrepancy between protein expression and enzymatic activity was observed for NAD-degrading CD38 on SLE B cells. No differences were found in the rate of extracellular ATP degradation and expression of CD39, CD203a/c, and CD157. DNA sequencing identified no coding variants in CD73 in SLE patients.

INTERPRETATION: We describe a new pathomechanism for SLE, by which inactivation of CD73 on B cells produces less anti-inflammatory adenosine, resulting in immune cell activation. CD73 inactivation was not due to genetic variation but may be related to posttranslational modification.

FUNDING: The German Research Council, Medical Faculty of the Heinrich-Heine-University Duesseldorf, Hiller Research Foundation, and Cardiovascular Research Institute Duesseldorf.

Copyright © 2021. Published by Elsevier B.V.

Keywords: Autoimmune disease; CD38; CD39; Metabolism; Purines

Conflict of interest statement

Declaration of competing interest None.

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