title: Fine specificity of anti-fibrillin-1 autoantibodies in primary pulmonary hypertension syndrome.
abstract: Autoantibodies to fibrillin-1 (Fbn-1) have been found in systemic sclerosis (SSc), calcinosis, Raynaud's esophagael dysmotility, sclerodectyly, and telaengectasia (CREST) and mixed connective tissue disease (MCTD) diseases. The purpose of this study was to determine whether patients with primary pulmonary hypertension (PPH) and appetite-suppressant-associated PPH have anti-Fbn-1 autoantibodies. In addition we assessed the human leucocyte antigen (HLA) class II alleles (DRB1, 3, 4, 5 and DQB1) in these patients in order to determine whether the response is genetically restricted. The frequency of anti-Fbn-1 autoantibodies in patient groups was compared with that of a control group of 88 healthy patients, and HLA was correlated similarly with a group of 51 healthy subjects. Anti-Fbn-1 autoantibodies were found at high frequency in PPH: in 70 of 75 adults with PPH (93%), in 28 of 33 children with PPH (84.8) and in 12 of 18 (67%) patients with appetite-suppressant-associated PPH. Utilization of two Fbn-1 fusion proteins allowed us to determine the dominant determinant region, recognized by anti-Fbn-1 autoantibodies, which may be located on the N-terminal fragment of the Fbn-1 protein. No significant immunogenetic correlations were found when the PPH patient groups were compared with normal controls. This novel category of autoantibodies is found in diseases characterized by endothelial and extracellular matrix protein alterations and fibrosis.
authors.affiliation: Division of Rheumatology, Department of Medicine, College of Physicians and Surgeons, Columbia University, NY 10029-6573, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Morse
authors.forename: S
authors.initials: S
authors.lastname: Antohi
authors.forename: K
authors.initials: K
authors.lastname: Kasturi
authors.forename: S
authors.initials: S
authors.lastname: Saito
authors.forename: M
authors.initials: M
authors.lastname: Fotino
authors.forename: M
authors.initials: M
authors.lastname: Humbert
authors.forename: G
authors.initials: G
authors.lastname: Simonneau
authors.forename: R J
authors.initials: RJ
authors.lastname: Basst
authors.forename: C A
authors.initials: CA
authors.lastname: Bona
mesh_terms: D000328:Adult; D000483:Alleles; D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000737:chemistry*; D002648:Child; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006650:Histocompatibility Testing; D006801:Humans; D006976:Hypertension, Pulmonary / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000276:immunology*; D013577:Syndrome; D054392:Adipokines
chemical_list: D001323:Autoantibodies; D000071838:Fibrillin-1; D000071837:Fibrillins; D000949:Histocompatibility Antigens Class II; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines; C000605724:Fbn1 protein, mouse