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).
The aim of our study is to characterize PTX3-specific (PTX3+) B cells in peripheral blood of SLE patients with or without LN and healthy donors (HD).
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 (figure 1). 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) (figure 2).
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
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