Background/Purpose: Anti-endothelial cell antibodies (AECA) are antibodies detected in multiple autoimmune and inflammatory diseases. Increased levels of such antibodies may be involved in disease activity and/or the coexistence of vasculitis. Juvenile dermatomyositis (JDM) shows many pathological features of vasculitis. Many autoantibodies detected in JDM have specific clinical and phenotypic associations, but their relationship to disease pathology remains unclear. Juvenile idiopathic arthritis (JIA) is a heterogeneous group of inflammatory diseases. There are no useful autoantibody biomarkers for diagnosis or for characterization of the disease. We aimed to detect target antigens for AECA and to investigate the roles of AECA in both diseases.

Methods: We screened plasma from pediatric rheumatic diseases (3 children with JDM and 2 children with polyarticular JIA) and from healthy children for the presence of AECA by western blotting and two-dimensional electrophoresis (2DE) using proteins extracted from human aortic endothelial cells (HAEC) as the substrate. Selected antigens were positive only in plasma of children with pediatric rheumatic diseases but not in plasma of healthy children. We performed mass spectrometry to identify the candidate antigens from 2DE gels and used ELISA assays to confirm the presence of specific antibodies.

Results: We successfully identified more than 600 proteins that were candidate targets of AECA in JIA and JDM using proteomics. Among these antigens were proteins regulating cellular redox processes. These included peroxiredoxins (Prxs), a family of related antioxidant enzymes. Using ELISA assays, IgG autoantibodies to Prx2 were detected in 12% of the patients with JDM (n=51) but not in healthy children (n=20). However, 24% of JDM patients with active disease (n=25) had anti-Prx2 antibodies, while these antibodies were absent (p<0.01) in JDM patients with inactive disease (n=26). We also noted that 17% of JIA patients with active disease (n=12) had anti-Prx2 antibodies. There was no difference in the frequency of anti-Prx2 antibodies between JIA patients with active disease and those with inactive disease. Another group of antigens that were detected were tropomyosins, a family of actin filament binding proteins, which are categorized into muscle isoforms and non-muscle isoforms. IgG autoantibodies to tropomyosin beta chain (TPM2) were detected in 24% of the patients with JIA (n=17) in contrast to 5% of healthy children (n=20). Interestingly, IgG autoantibodies to TPM2 were detected in 43% of the untreated JIA patients with active disease (n=7) in contrast to 5% (p<0.05) of healthy children. On the other hand, 15 % of JDM patients (n=20) had anti-TPM2 antibodies.

Conclusion: IgG antibodies to Prx2 and TPM2 in the proteome of HAEC are present in the children with JDM and with JIA. The measurement of anti-Prx2 antibodies might be useful for evaluation of disease activity in JDM.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-endothelial-cell-antibodies-in-pediatric-rheumatic-diseases/