Lack of circulating autoantibodies to bone morphogenetic protein receptor-II or activin receptor-like kinase 1 in mixed connective tissue disease patients with pulmonary arterial hypertension.
OBJECTIVE
To examine whether autoantibodies against bone morphogenetic protein receptor-II (BMPR-II) or activin receptor-like kinase 1 (ALK-1) are associated with pulmonary arterial hypertension (PAH) in patients with mixed connective tissue disease (MCTD).


METHODS
We studied sera from 37 MCTD patients with or without PAH, six patients with idiopathic PAH, and 30 healthy controls. Circulating anti-BMPR-II and anti-ALK-1 antibodies were detected using immunoprecipitation of recombinant antigens generated by in vitro transcription/translation and indirect immunofluorescence of cultured cells that were induced to express these antigens by gene transfer. Anti-BMPR-II antibodies were further examined by immunoprecipitation and immunoblotting using a recombinant fragment of the extracellular domain of BMPR-II.


RESULTS
Serum anti-BMPR-II and anti-ALK-1 autoantibodies were not detected in MCTD patients irrespective of the presence or absence of PAH, or in patients with idiopathic PAH.


CONCLUSIONS
Our finding does not support the hypothesis that autoantibody-mediated dysregulation of signals through BMPR-II or ALK-1 contributes to the development of PAH in patients with connective tissue diseases.
Satoh
T
T
Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Kimura
K
K
Okano
Y
Y
Hirakata
M
M
Kawakami
Y
Y
Kuwana
M
M
D030201:Activin Receptors, Type I / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D052006:Bone Morphogenetic Protein Receptors, Type II; D002478:Cells, Cultured; D019084:Fluorescent Antibody Technique, Indirect / Q000379:methods; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000276:immunology*; D015151:Immunoblotting / Q000379:methods; D008947:Mixed Connective Tissue Disease / Q000150:complications / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology
D001323:Autoantibodies; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II