Journal article
Characterization of pathogenic human monoclonal autoantibodies against GM-CSF
Y Wang, CA Thomson, LL Allan, LM Jackson, M Olson, TR Hercus, TL Nero, A Turner, MW Parker, AL Lopez, TK Waddell, GP Anderson, JA Hamilton, JW Schrader
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2013
Abstract
The origin of pathogenic autoantibodies remains unknown. Idiopathic pulmonary alveolar proteinosis is caused by autoantibodies against granulocyte-macrophage colony-stimulating factor (GMCSF). We generated 19 monoclonal autoantibodies against GMCSF from six patients with idiopathic pulmonary alveolar proteinosis. The autoantibodies used multiple V genes, excluding preferred V-gene use as an etiology, and targeted at least four nonoverlapping epitopes on GM-CSF, suggesting that GM-CSF is driving the autoantibodies and not a B-cell epitope on a pathogen cross-reacting with GM-CSF. The number of somatic mutations in the autoantibodies suggests that the memory B cells have been helped by T cells..
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Awarded by National Health and Medical Research Council of Australia (NHMRC)
Funding Acknowledgements
We thank the staff of the Royal Melbourne Hospital and the Toronto General Hospital; Dr. John Seymour; Dr. Christopher Brown; and the University of British Columbia Centre for Biothermodynamics. This study was supported by the Canadian Institutes of Health Research and the Canadian Arthritis Network (J.W.S.); by a National Health and Medical Research Council of Australia (NHMRC) Development Grant (to J.A.H., J.W.S., and G.P.A.) and Program Grant 565217 (to A.L.); and infrastructure support from the Victorian State Government Operational Infrastructure Support Program (M.W.P.). J.W.S. is a Canada Research Chair and M.W.P. and J.A.H. are Senior Principal Research Fellows of the NHMRC.