Identification of 4-Trimethylaminobutyraldehyde Dehydrogenase (TMABA-DH) as a Candidate Serum Autoantibody Target for Kawasaki Disease

PLoS One. 2015 May 26;10(5):e0128189. doi: 10.1371/journal.pone.0128189. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Oxidoreductases / blood
  • Aldehyde Oxidoreductases / immunology*
  • Animals
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Autoantigens / blood
  • Autoantigens / immunology*
  • Child
  • Child, Preschool
  • Female
  • HEK293 Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Infant
  • Male
  • Mucocutaneous Lymph Node Syndrome / blood
  • Mucocutaneous Lymph Node Syndrome / diagnosis
  • Mucocutaneous Lymph Node Syndrome / immunology*
  • Myocytes, Cardiac / immunology*
  • Myocytes, Cardiac / metabolism
  • Myosin Light Chains / immunology
  • Myosin Light Chains / metabolism
  • Rats

Substances

  • Autoantibodies
  • Autoantigens
  • Myosin Light Chains
  • 4-N-trimethylaminobutyraldehyde dehydrogenase
  • Aldehyde Oxidoreductases

Grants and funding

This research was funded by the Ministry of Health, Labour and Welfare, Japan to SH (2009 to 2011, Health and Labour Sciences Research Grants to The Study Group for Treatment Guideline on Refractory Kawasaki Disease, SH is a member of The Study Group). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.