Circulating Pentraxin3-Specific B Cells Are Decreased in Lupus Nephritis

Mariele Gatto, Annika Wiedemann, Nadja Nomovi, Karin Reiter, Eva Schrezenmeier, Thomas Rose, Franziska Szelinski, Andreia C Lino, Sonia Valentino, Anna Ghirardello, Thomas Dörner, Andrea Doria

Research output: Contribution to journalArticle

Abstract

Background: Pentraxin3 (PTX3) is overexpressed in kidneys of patients developing lupus nephritis (LN). Active LN is associated with reduced anti-PTX3 antibodies. However, abnormalities of B cell differentiation against PTX3 have not been characterized in systemic lupus erythematosus (SLE). Objective: Characterization of PTX3-specific (PTX3+) B cells in peripheral blood of SLE patients with or without LN and healthy donors (HD). Patients and Methods: SLE patients without LN, biopsy-proven LN and matched HD were analyzed. Active LN was defined as proteinuria>0.5 g/day or CrCl<60 ml/min/1.73 m2 with active urinary sediment. Peripheral B cells were analyzed for direct PTX3 binding by flow cytometry using PTX3 labeled with cyanine 5 (Cy5) and phycoerythrin (PE). Results: Initially, a flow cytometry based assay to identify PTX3+ B cells was developed by demonstrating simultaneous binding of PTX3-Cy5 and PTX3-PE. Specificity of B cells was validated by blocking experiments using unlabeled PTX3. We could identify circulating PTX3+ B-cells in HD and patients. Notably, LN patients showed a significantly diminished number of PTX3+ B cells (SLE vs. LN p = 0.033; HD vs. LN p = 0.008). This decrease was identified in naïve and memory B cell compartments (naïve: SLE vs. LN p = 0.028; HD vs. LN p = 0.0001; memory: SLE vs. LN p = 0.038, HD vs. LN p = 0.011). Conclusions: Decreased PTX3+ B cells in LN within the naïve and memory compartment suggest their negative selection at early stages of B cell development potentially related to a decreased regulatory function. PTX3+ B cells could candidate for autoantigen-defined regulatory B cells as a striking abnormality of LN patients.

Original languageEnglish
Pages (from-to)29
JournalFrontiers in Immunology
Volume10
DOIs
Publication statusPublished - 2019

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Keywords

  • Adult
  • Autoantibodies/blood
  • Autoantigens/metabolism
  • B-Lymphocytes/metabolism
  • Biomarkers/metabolism
  • C-Reactive Protein/chemistry
  • Carbocyanines/chemistry
  • Female
  • Flow Cytometry/methods
  • Humans
  • Lupus Erythematosus, Systemic/blood
  • Lupus Nephritis/blood
  • Male
  • Middle Aged
  • Phycoerythrin/chemistry
  • Serum Amyloid P-Component/chemistry
  • Staining and Labeling

Cite this

Gatto, M., Wiedemann, A., Nomovi, N., Reiter, K., Schrezenmeier, E., Rose, T., Szelinski, F., Lino, A. C., Valentino, S., Ghirardello, A., Dörner, T., & Doria, A. (2019). Circulating Pentraxin3-Specific B Cells Are Decreased in Lupus Nephritis. Frontiers in Immunology, 10, 29. https://doi.org/10.3389/fimmu.2019.00029