RT Journal Article
SR Electronic
T1 An Open-Label Trial of Rituximab Therapy in Pulmonary Alveolar Proteinosis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP erj01977-2010
DO 10.1183/09031936.00197710
A1 M.S. Kavuru
A1 A. Malur
A1 I. Marshall
A1 B.P. Barna
A1 M. Meziane
A1 I. Huizar
A1 H. Dalrymple
A1 R. Karnekar
A1 M.J. Thomassen
YR 2011
UL http://erj.ersjournals.com/content/early/2011/04/07/09031936.00197710.abstract
AB Rituximab, a monoclonal antibody directed against the B-lymphocyte antigen CD20, has shown promise in several autoimmune disorders. Pulmonary Alveolar Proteinosis (PAP) is an autoimmune disorder characterized by autoantibodies to Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF).An open label proof-of-concept Phase II clinical trial was conducted in 10 PAP patients. Intervention consisted of two intravenous infusions of rituximab (1000 mg), fifteen days apart. Bronchoalveolar lavage (BAL) and peripheral blood samples were collected.The primary outcome was improvement in arterial blood oxygenation. Both Pa,O2 and A-a gradient on room air improved in 7/9 patients completing the study. Lung function and HRCT scans, secondary outcomes, also improved. Peripheral blood CD19+ B-lymphocytes decreased from 15±2% to <0.05% (n=10) fifteen days post therapy. This decrease persisted for 3 months in all patients; at six months CD19+ were detected in 4/7 patients (mean 5±2). Total anti-GM-CSF IgG levels from baseline to 6 months were decreased in BAL fluids (n=8), but unchanged in sera (n=9).In this PAP cohort, (1) rituximab was well-tolerated and effectively ameliorated lung disease; (2) reduction in anti-GM-CSF IgG levels in the lung correlated with disease changes suggesting that disease pathogenesis is related to autoantibody levels in the target organ.