Marco Lanzillotta1, Emanuel Della-Torre2, Raffaella Milani3, Enrica Bozzolo4, Emanuele Bozzalla-Cassione1, Lucrezia Rovati1, Paolo Giorgio Arcidiacono5, Stefano Partelli6, Massimo Falconi6, Fabio Ciceri7, Lorenzo Dagna1. 1. Università Vita-Salute San Raffaele and Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy. 2. Università Vita-Salute San Raffaele and Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy. dellatorre.emanuel@hsr.it. 3. Unit of Immunohaematology and Transfusion Medicine, IRCCS San Raffaele Scientific Institute, Milan, Italy. 4. Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS-San Raffaele Scientific Institute, Milan, Italy. 5. Università Vita-Salute San Raffaele and Pancreato-Biliary Endoscopy and Endosonography Division, IRCCS San Raffaele Scientific Institute, Milan, Italy. 6. Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Centre, IRCCS San Raffaele Scientific Institute, Milan, Italy. 7. Università Vita-Salute San Raffaele and Haematology and Bone Marrow Trasplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Abstract
OBJECTIVES: Glucocorticoids induce prompt clinical improvement in patients with IgG4-related disease (IgG4-RD) but their mechanisms of action in this specific condition are not fully understood. B lymphocytes appear central to IgG4-RD pathogenesis because B-cell depletion with rituximab leads to swift clinical responses. In the present work we aim to assess the effects of glucocorticoids on B-cell subpopulations in patients with IgG4-RD. METHODS: Fifty patients with active untreated IgG4-RD and 20 healthy controls were enrolled in the present study. Flow cytometry analysis for total circulating CD19+ and CD20+ cells, naïve B cells, memory B cells, plasmablasts, and plasma cells was performed at baseline in all patients, and after 6 months of glucocorticoid treatment in 30 patients. Correlation studies with biomarkers of disease activity were also performed. RESULTS: At baseline, patients with IgG4-RD showed reduced CD19+ and CD20+ B cells compared to healthy controls, but increased circulating plasmablasts and plasma cells. Circulating plasmablasts and plasma cells correlated with clinical and serological biomarkers of IgG4-RD activity. Glucocorticoid-induced disease remission was accompanied by a reduction of naïve B cell count, an increase of memory B cells, and by a depletion of circulating plasmablasts and plasma cells. CD19+ and CD20+ B cells, were not affected by glucocorticoids. CONCLUSIONS: The efficacy of glucocorticoids in IgG4-RD is associated with selective effects on different B-cell subpopulations. Further studies are warranted to fully understand possible perturbations of the naïve and memory B-cell compartments in patients with IgG4-RD.
OBJECTIVES: Glucocorticoids induce prompt clinical improvement in patients with IgG4-related disease (IgG4-RD) but their mechanisms of action in this specific condition are not fully understood. B lymphocytes appear central to IgG4-RD pathogenesis because B-cell depletion with rituximab leads to swift clinical responses. In the present work we aim to assess the effects of glucocorticoids on B-cell subpopulations in patients with IgG4-RD. METHODS: Fifty patients with active untreated IgG4-RD and 20 healthy controls were enrolled in the present study. Flow cytometry analysis for total circulating CD19+ and CD20+ cells, naïve B cells, memory B cells, plasmablasts, and plasma cells was performed at baseline in all patients, and after 6 months of glucocorticoid treatment in 30 patients. Correlation studies with biomarkers of disease activity were also performed. RESULTS: At baseline, patients with IgG4-RD showed reduced CD19+ and CD20+ B cells compared to healthy controls, but increased circulating plasmablasts and plasma cells. Circulating plasmablasts and plasma cells correlated with clinical and serological biomarkers of IgG4-RD activity. Glucocorticoid-induced disease remission was accompanied by a reduction of naïve B cell count, an increase of memory B cells, and by a depletion of circulating plasmablasts and plasma cells. CD19+ and CD20+ B cells, were not affected by glucocorticoids. CONCLUSIONS: The efficacy of glucocorticoids in IgG4-RD is associated with selective effects on different B-cell subpopulations. Further studies are warranted to fully understand possible perturbations of the naïve and memory B-cell compartments in patients with IgG4-RD.
Authors: J-Matthias Löhr; Ulrich Beuers; Miroslav Vujasinovic; Domenico Alvaro; Jens Brøndum Frøkjær; Frank Buttgereit; Gabriele Capurso; Emma L Culver; Enrique de-Madaria; Emanuel Della-Torre; Sönke Detlefsen; Enrique Dominguez-Muñoz; Piotr Czubkowski; Nils Ewald; Luca Frulloni; Natalya Gubergrits; Deniz Guney Duman; Thilo Hackert; Julio Iglesias-Garcia; Nikolaos Kartalis; Andrea Laghi; Frank Lammert; Fredrik Lindgren; Alexey Okhlobystin; Grzegorz Oracz; Andrea Parniczky; Raffaella Maria Pozzi Mucelli; Vinciane Rebours; Jonas Rosendahl; Nicolas Schleinitz; Alexander Schneider; Eric Fh van Bommel; Caroline Sophie Verbeke; Marie Pierre Vullierme; Heiko Witt Journal: United European Gastroenterol J Date: 2020-06-18 Impact factor: 4.623