Marcella Visentini1,2, Martina Del Padre1, Stefania Colantuono1, Baoran Yang1, Ylenia Aura Minafò1, Silvia Antonini1, Myriam Carnovale1, Adriano De Santis3, Alessandro Pulsoni4, Giuseppe Maria De Sanctis5, Laura Gragnani6, Anna Linda Zignego6, Massimo Fiorilli1, Milvia Casato1. 1. Division of Clinical Immunology, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy. 2. Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy. 3. Division of Gastroenterology and Hepatology, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy. 4. Division of Hematology, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy. 5. Division of Infectious Diseases, Sapienza University of Rome, Rome, Italy. 6. Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), University of Florence, Florence, Italy.
Abstract
BACKGROUND & AIMS: Hepatitis C virus (HCV)-related mixed cryoglobulinaemia vasculitis (MCV) is characterized by the expansion of rheumatoid factor-producing B-cell clones. The aim of this study was to assess whether B-cell clones may persist in these patients after the clearance of the virus with antiviral therapy, and whether their persistence influences clinical outcomes. METHODS: Forty-five HCV-cured MCV patients were followed up for a median of 18.5 (range 9-38) months after the clearance of HCV. Circulating B-cell clones were detected using flow cytometry either by the skewing of kappa/lambda ratio or by the expression of a VH 1-69-encoded idiotype. RESULTS: The clinical response of vasculitis was 78% complete, 18% partial and 4% null. However, cryoglobulins remained detectable in 42% of patients for more than 12 months. Circulating B-cell clones were detected in 18 of 45 patients, and in 17 of them persisted through the follow-up; nine of the latter patients cleared cryoglobulins and had complete response of vasculitis. Several months later, two of these patients had relapse of MCV. CONCLUSIONS: B-cell clones persist in MCV patients long after HCV infection has been cleared but halt the production of pathogenic antibody. These 'dormant' cells may be reactivated by events that perturb B-cell homeostasis and can give rise to the relapse of cryoglobulinaemic vasculitis.
BACKGROUND & AIMS:Hepatitis C virus (HCV)-related mixed cryoglobulinaemia vasculitis (MCV) is characterized by the expansion of rheumatoid factor-producing B-cell clones. The aim of this study was to assess whether B-cell clones may persist in these patients after the clearance of the virus with antiviral therapy, and whether their persistence influences clinical outcomes. METHODS: Forty-five HCV-cured MCV patients were followed up for a median of 18.5 (range 9-38) months after the clearance of HCV. Circulating B-cell clones were detected using flow cytometry either by the skewing of kappa/lambda ratio or by the expression of a VH 1-69-encoded idiotype. RESULTS: The clinical response of vasculitis was 78% complete, 18% partial and 4% null. However, cryoglobulins remained detectable in 42% of patients for more than 12 months. Circulating B-cell clones were detected in 18 of 45 patients, and in 17 of them persisted through the follow-up; nine of the latter patients cleared cryoglobulins and had complete response of vasculitis. Several months later, two of these patients had relapse of MCV. CONCLUSIONS: B-cell clones persist in MCV patients long after HCV infection has been cleared but halt the production of pathogenic antibody. These 'dormant' cells may be reactivated by events that perturb B-cell homeostasis and can give rise to the relapse of cryoglobulinaemic vasculitis.
Authors: Mahmood Danishwar; Zahid Jamil; Salman Khan; Michael Nakhla; Ishtiaq Ahmad; Muhammad Ashar Ali; Daryl T Y Lau Journal: J Clin Med Date: 2022-02-14 Impact factor: 4.241
Authors: Loreta A Kondili; Monica Monti; Maria Giovanna Quaranta; Laura Gragnani; Valentina Panetta; Giuseppina Brancaccio; Cesare Mazzaro; Marcello Persico; Mario Masarone; Ivan Gentile; Pietro Andreone; Salvatore Madonia; Elisa Biliotti; Roberto Filomia; Massimo Puoti; Anna Ludovica Fracanzani; Diletta Laccabue; Donatella Ieluzzi; Carmine Coppola; Maria Grazia Rumi; Antonio Benedetti; Gabriella Verucchi; Barbara Coco; Liliana Chemello; Andrea Iannone; Alessia Ciancio; Francesco Paolo Russo; Francesco Barbaro; Filomena Morisco; Luchino Chessa; Marco Massari; Pierluigi Blanc; Anna Linda Zignego Journal: Hepatology Date: 2022-01-19 Impact factor: 17.298