title: Identification of 4-Trimethylaminobutyraldehyde Dehydrogenase (TMABA-DH) as a Candidate Serum Autoantibody Target for Kawasaki Disease.
abstract: Kawasaki disease (KD), an acute vasculitis that preferentially affects coronary arteries, is still the leading cause of acquired heart disease in children. Although the involvement of immune system malfunction in the onset of KD is suggested, its etiology still remains to be clarified. We investigated autoantibodies in KD patients, which are frequently found in sera from patients with autoimmune diseases, vasculitides and arteritides. We performed two-dimensional western blotting and LC-MS/MS to analyze the antigens of autoantibodies, detected two protein spots with 4 out of 24 sera from KD patients but not with 6 control sera, and identified the antigens as 4-trimethylaminobutyraldehyde dehydrogenase (TMABA-DH). A slot blot analysis with TMABA-DH as an antigen also revealed higher reactivities of patients' sera than control sera (positive rates: 18/43 vs 3/41). Using an enzyme-linked immunosorbent assay (ELISA), we found that the reactivity of anti-TMABA-DH antibodies in sera from KD patients was significantly higher than that in sera from age-matched controls. The optimal cut-off value of 0.043 had a sensitivity of 83.7% and a specificity of 80.0% in detecting KD patients (positive rates: 37/43 for KD patients, 9/41 for controls). Immunohistochemistry performed on thin sections of rat heart revealed that TMABA-DH colocalized with myosin light chains in cardiac myocytes. Patient sera with high reactivity gave similar immunostaining pattern. These results suggest that the detection of anti-TMABA-DH autoantibody could be a potential strategy for a diagnosis of KD.
authors.affiliation: Division of Cellular Proteomics, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan; Division of Biochemistry, School of Pharmaceutical Sciences, Kitasato University, Minato-ku, Tokyo, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Matsunaga
authors.affiliation: Division of Cellular Proteomics, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan; Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Harita
authors.affiliation: Division of Biochemistry, School of Pharmaceutical Sciences, Kitasato University, Minato-ku, Tokyo, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Shibagaki
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Shimizu
authors.affiliation: Tokyo Metropolitan Children's Medical Center, Fuchu, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Shibuya
authors.affiliation: National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ono
authors.affiliation: National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kato
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan; Department of Pediatrics, Ohashi Hospital, Toho University School of Medicine, Meguro-ku, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sekine
authors.affiliation: National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Sakamoto
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan; National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Igarashi
authors.affiliation: Division of Cellular Proteomics, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan; Division of Biochemistry, School of Pharmaceutical Sciences, Kitasato University, Minato-ku, Tokyo, Japan.
authors.forename: Seisuke
authors.initials: S
authors.lastname: Hattori
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000097:blood / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000097:blood / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007223:Infant; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D032383:Myocytes, Cardiac / Q000276:immunology* / Q000378:metabolism; D018994:Myosin Light Chains / Q000276:immunology / Q000378:metabolism; D051381:Rats
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D018994:Myosin Light Chains; C023095:4-N-trimethylaminobutyraldehyde dehydrogenase; D000445:Aldehyde Oxidoreductases