Skewed peripheral B- and T-cell compartments in patients with ANCA-associated vasculitis

• Published in: Rheumatology (Oxford, England) Vol. 60; no. 5; pp. 2157 - 2168
• Main Authors: London, Jonathan, Dumoitier, Nicolas, Lofek, Sébastien, Dion, Jérémie, Chaigne, Benjamin, Mocek, Julie, Thieblemont, Nathalie, Cohen, Pascal, Le Jeunne, Claire, Guillevin, Loïc, Witko-Sarsat, Véronique, Varin-Blank, Nadine, Terrier, Benjamin, Mouthon, Luc
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 14.05.2021; Oxford University Press (OUP)
• Series: Rheumatology
• Subjects: Human health and pathology; Life Sciences; B-lymphocyte; T-lymphocyte; granulomatosis with polyangiitis (GPA); microscopic polyangiitis; neutrophils; ANCA-associated vasculitis
• ISSN: 1462-0324; 1462-0332; 1462-0332
• DOI: 10.1093/rheumatology/keaa432

Abstract Objectives To characterize lymphocytes dysregulation in patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Methods Using flow cytometry, we analysed B- and T-cell subsets in peripheral blood from 37 untreated patients with active disease (29 GPA and 8 MPA) and 22 healthy controls (HCs). Results GPA patients had increased Th2 (1.8 vs 1.0%, P = 0.02), Th9 (1.1 vs 0.2%, P = 0.0007) and Th17 (1.4 vs 0.9%, P = 0.03) cells compared with HC. Patients with MPO-ANCAs had significantly more CD21– B cells than HC or PR3-ANCA patients (6.9 vs 3.3% and 4.4%, P = 0.01). CD69 expressing B cells were significantly higher in GPA and MPA (3.0 and 5.9 vs 1.4%, P = 0.02 and P = 0.03, respectively) compared with HC, whereas B-cell activating factor-receptor expression was decreased in GPA and MPA (median fluorescence intensity ratio 11.8 and 13.7 vs 45.1 in HC, P < 0.0001 and P = 0.003, respectively). Finally, IL-6-producing B cells were increased in GPA vs HC (25.8 vs 14.9%, P < 0.0001) and decreased in MPA vs HC (4.6 vs 14.9%, P = 0.005), whereas TNF-α-producing B cells were lower in both GPA and MPA patients compared with controls (15 and 8.4 vs 30%, P = 0.01 and P = 0.006, respectively). Conclusion Skewed T-cell polarization towards Th2, Th9 and Th17 responses characterizes GPA, whereas B-cell populations are dysregulated in both GPA and MPA with an activated phenotype and a decreased B-cell activating factor-receptor expression. Finally, inflammatory B cells producing IL-6 are dramatically increased in GPA, providing an additional mechanism by which rituximab could be effective.