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Σάββατο 2 Σεπτεμβρίου 2017

Identification and phenotyping of circulating autoreactive proteinase 3-specific B cells in patients with PR3-ANCA associated vasculitis and healthy controls

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Publication date: Available online 1 September 2017
Source:Journal of Autoimmunity
Author(s): Divi Cornec, Alvise Berti, Amber Hummel, Tobias Peikert, Jacques-Olivier Pers, Ulrich Specks
ObjectivesTo develop a method to detect and phenotype circulating proteinase 3 (PR3)-specific B-cells in patients with PR3-ANCA associated vasculitis (AAV).MethodsRecombinant human PR3 (rPR3) was tagged with FITC or biotin, and its binding characteristics were studied by flow cytometry using three hybridoma cell lines secreting antibodies (Ab) against human PR3, mouse PR3 (no cross-reactivity with human PR3), and human neutrophil elastase. We measured the proportion of PR3-specific B-cells and studied their surface phenotype in patients with PR3-AAV and healthy controls (HC).ResultsLabeled rPR3 efficiently and specifically bound to hybridoma cells producing anti-human-PR3-Ab but not anti-mouse-PR3-Ab or anti-human-elastase-Ab. The proportion of rPR3-stained B cells was higher in patients with PR3-AAV compared to HCs: median (IQR) 1.11% (0.81–2.43) vs 0.45% (0.26–0.62) respectively, p < 0.001. There was a trend towards a higher proportion of PR3-specific B cells among patients with active disease compared to patients in remission: 2.91% (1.18–6.52) vs 0.99% (0.72–1.58), p = 0.09. In HCs, the proportion of PR3-specific B cells was highest among the transitional B-cell subset, and decreased with the maturation of B cells. Conversely, in patients, the proportion of PR3-specific B cells progressively increased with the maturation of B cells (median 1.90% of naïve B cells, 2.30% of unswitched memory B cells, 2.37% of switched memory B cells, and 3.68% of plasmablasts).ConclusionsCirculating PR3-specific B cells can be detected in HC and patients with PR3-AAV. Their progressive enrichment during B-cell maturation suggests that they are actively selected and escape peripheral tolerance checkpoints in patients.



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