Fine specificity of anti-fibrillin-1 autoantibodies in primary pulmonary hypertension syndrome

Autoantibodies to fibrillin-1 (Fbn-1) have been found in systemic sclerosis (SSc), calcinosis, Raynaud's esophagael dysmotility, sclerodectyly, and te laengectasia (CREST) and mixed connective tissue disease (MCTD) diseases. T he purpose of this study was to determine whether patients with primary pul monary 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 hi gh frequency in PPH: in 70 of 75 adults with PPH (93%), in 28 of 33 childre n 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 dete rmine the dominant determinant region, recognized by anti-Fbn-1 autoantibod ies, which may be located on the N-terminal fragment of the Fbn-1 protein. No significant immunogenetic correlations were found when the PPH patient g roups were compared with normal controls. This novel category of autoantibo dies is found in diseases characterized by endothelial and extracellular ma trix protein alterations and fibrosis.