title: Suppression of activin A in autoimmune lung disease associated with anti-GM-CSF.
abstract: Pulmonary alveolar proteinosis (PAP) is an autoimmune disorder characterized by neutralizing autoantibodies to granulocyte-macrophage colony stimulating factor (GM-CSF). Surfactant metabolism is severely dysregulated in PAP, resulting in a foam cell appearance of alveolar macrophages. Microarray analysis of RNA from PAP bronchoalveolar lavage (BAL) cells to explore autoimmune-related genes yielded evidence of a deficiency of activin A, a cytokine implicated in regulation of B-cell proliferation and reduction of foam cell formation. Subsequent studies confirmed a severe deficiency of activin A gene expression and protein secretion in PAP BAL cells and marked reduction of activin A protein in PAP BAL fluids compared to healthy controls. PAP cells, however, like those of healthy controls, were capable of elevated activin A production in response to GM-CSF. Treatment with activin A in vitro suppressed proliferation of PAP peripheral blood B-cells in a receptor-dependent manner and also reduced secretion of anti-GM-CSF autoantibody. These studies are the first to suggest that activin A may play a role in autoimmune disease.
authors.affiliation: Department of Pulmonary, Allergy and Critical Care Medicine, Cleveland, OH, USA.
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Bonfield
authors.forename: Barbara P
authors.initials: BP
authors.lastname: Barna
authors.forename: Nejimol
authors.initials: N
authors.lastname: John
authors.forename: Anagha
authors.initials: A
authors.lastname: Malur
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Culver
authors.forename: Mani S
authors.initials: MS
authors.lastname: Kavuru
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Thomassen
mesh_terms: D028341:Activins / Q000172:deficiency* / Q000235:genetics* / Q000494:pharmacology; D000328:Adult; D001323:Autoantibodies / Q000096:biosynthesis*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics; D001402:B-Lymphocytes / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D028322:Inhibin-beta Subunits / Q000172:deficiency* / Q000235:genetics* / Q000494:pharmacology; D008297:Male; D011649:Pulmonary Alveolar Proteinosis / Q000235:genetics / Q000276:immunology*
chemical_list: D001323:Autoantibodies; C422405:activin A; D028341:Activins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D028322:Inhibin-beta Subunits