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

TITLE=Circulating Pentraxin3-Specific B Cells Are Decreased in Lupus Nephritis

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00029

DOI=10.3389/fimmu.2019.00029

ISSN=1664-3224

ABSTRACT=<p><bold>Background:</bold> 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).</p><p><bold>Objective:</bold> Characterization of PTX3-specific (PTX3<sup>+</sup>) B cells in peripheral blood of SLE patients with or without LN and healthy donors (HD).</p><p><bold>Patients and Methods:</bold> SLE patients without LN, biopsy-proven LN and matched HD were analyzed. Active LN was defined as proteinuria&gt;0.5 g/day or CrCl&lt;60 ml/min/1.73 m<sup>2</sup> 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).</p><p><bold>Results:</bold> Initially, a flow cytometry based assay to identify PTX3<sup>+</sup> 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<sup>+</sup> B-cells in HD and patients. Notably, LN patients showed a significantly diminished number of PTX3<sup>+</sup> B cells (SLE vs. LN <italic>p</italic> = 0.033; HD vs. LN <italic>p</italic> = 0.008). This decrease was identified in naïve and memory B cell compartments (naïve: SLE vs. LN <italic>p</italic> = 0.028; HD vs. LN <italic>p</italic> = 0.0001; memory: SLE vs. LN <italic>p</italic> = 0.038, HD vs. LN <italic>p</italic> = 0.011).</p><p><bold>Conclusions:</bold> Decreased PTX3<sup>+</sup> 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<sup>+</sup> B cells could candidate for autoantigen-defined regulatory B cells as a striking abnormality of LN patients.</p>