Session Information
Date: Thursday, May 18, 2017
Session Type: Abstract Submissions
Session Time: 4:45PM-5:15PM
Background/Purpose: Juvenile dermatomyositis (JDM) is the most common form of inflammatory myopathy in children. Although classified as a myopathy, involved tissues in JDM are characterized by prominent vascular and perivascular inflammation that are believed to be directly involved in the clinical features of the disease. Thus, JDM also can be characterized as a form of vasculitis. Anti-endothelial cell antibodies (AECA) are detected in multiple autoimmune, infectious, and inflammatory diseases, including vasculitis. We aimed to determine whether such antibodies are present in JDM and, if so, to comprehensively detect their target antigens using a proteomics approach. Methods: To detect antibodies in sera from patients with JDM, proteins extracted from human aortic endothelial cells (HAEC) were used as antigen sources by SDS-PAGE and immunoblotting. To comprehensively detect target antigens for AECA, we separated proteins extracted from HAEC by two-dimensional electrophoresis (2DE) and then transferred them onto membranes. Autoantigens that were positive only in sera from children with JDM but not in sera from healthy children were detected by western blotting (WB). The detected proteins were then identified by mass spectrometry (MS). Bound IgG antibodies to antigens were detected using standard methods. Results: Five candidate protein spots as JDM-specific proteins were detected in 2DE-WB. From these spots, we successfully identified 34 proteins which we characterized broadly according to their functions: (1) 62% were ATP-related proteins such as proteins of the tricarboxylic acid (TCA) cycle (e.g., pyruvate kinase PKM and 78kDa glucose-regulated protein; (2) 21% were muscle-related proteins, including myosin-9 and Cdc42-interacting protein 4; (3) 18% were calcium regulated proteins and/or calcium binding proteins (e.g., annexin A6 and N-acetylglucosamine-6-sulfatase). We also identified eight proteins that act as chaperones or co-chaperones in intracellular protein trafficking. Furthermore 22 of the 34 identified antigens represented membrane proteins. Using Ingenuity Pathway Analysis (IPA), 27 of the 34 candidate target antigens for AECA in JDM were predicted to interact with chaperone proteins, which regulate the correct folding, stabilization, and translocation of proteins. Conclusion: IgG antibodies to proteins in the proteome of HAEC are present in the sera of JDM. The presence of AECA in JDM could implicate these antibodies in the pathobiology of the vascular/perivascular inflammation that is a proment feature of JDM.
Disclosure: R. Karasawa, None; M. Tamaki, None; T. Sato, None; M. Tanaka, None; K. Yudoh, None; J. Jarvis, None.
To cite this abstract in AMA style:
Karasawa R, Tamaki M, Sato T, Tanaka M, Yudoh K, Jarvis J. Anti-endothelial cell antibodies in juvenile dermatomyositis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 4). https://acrabstracts.org/abstract/anti-endothelial-cell-antibodies-in-juvenile-dermatomyositis/. Accessed .ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-endothelial-cell-antibodies-in-juvenile-dermatomyositis/