An open-label trial of rituximab therapy in pulmonary alveolar proteinosis.

Abstract

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 characterised 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. The intervention consisted of two intravenous infusions of rituximab (1,000 mg) 15 days apart. Bronchoalveolar lavage (BAL) fluid and peripheral blood samples were collected. The primary outcome was improvement in arterial blood oxygenation. Both arterial oxygen tension and alveolar-arterial oxygen tension difference in room air improved in seven out of the nine patients completing the study. Lung function and high-resolution computed tomography scans, which were secondary outcomes, also improved. Peripheral blood CD19+ B-lymphocytes decreased from mean ± sem 15 ± 2% to <0.05% (n = 10) 15 days post-therapy. This decrease persisted for 3 months in all patients; at 6 months, CD19+ B-cells were detected in four out of seven patients (5 ± 2%). Total anti-GM-CSF immunoglobulin (Ig)G 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; and 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.

• Authors: M S Kavuru, A Malur, I Marshall, B P Barna, M Meziane, I Huizar, H Dalrymple, R Karnekar, M J Thomassen
• Journal: The European respiratory journal (Eur Respir J) Vol. 38 Issue 6 Pg. 1361-7 (Dec 2011) ISSN: 1399-3003 [Electronic] England
• PMID: 21478218 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Antigens, CD19
• Autoantibodies
• Immunoglobulin G
• Immunologic Factors
• Rituximab
• Granulocyte-Macrophage Colony-Stimulating Factor
• Oxygen

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Murine-Derived (therapeutic use)
• Antigens, CD19 (blood)
• Autoantibodies (blood, immunology)
• Autoimmune Diseases (blood, drug therapy, immunology)
• B-Lymphocytes (drug effects, immunology)
• Bronchoalveolar Lavage Fluid (chemistry)
• Cohort Studies
• Female
• Granulocyte-Macrophage Colony-Stimulating Factor (antagonists & inhibitors, immunology)
• Humans
• Immunoglobulin G (blood, immunology)
• Immunologic Factors (therapeutic use)
• Lung (diagnostic imaging, immunology, physiology)
• Male
• Middle Aged
• Oxygen (blood)
• Pulmonary Alveolar Proteinosis (drug therapy, immunology)
• Radiography
• Rituximab
• Treatment Outcome
• Young Adult