Background/Purpose: Juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM) are among the most common forms of inflammatory rheumatic diseases in children. Anti-endothelial cell antibodies (AECA) are frequently detected in inflammatory, infectious, and autoimmune diseases. We therefore, used proteomic approaches to identify target antigens for AECA.

Methods: We screened plasma from children with JDM and polyarticular JIA (pJIA) for the presence of AECA by western blotting and 2D gel electrophoresis using proteins extracted from human aortic endothelial cells (HAEC). We performed mass spectrometry (MS) to identify autoantigens and used ELISA assays to corroborate the MS data, using plasma from 63 JDM patients, 50 pJIA patients and 40 sex- and age-matched healthy controls (HC).

Results: More than 600 proteins were identified as candidate targets of AECA in the plasma. Among these antigens were muscle proteins such as peroxiredoxin 6 (Prx6) and myosin light polypeptide 6 (MYL6). On ELISA assays, anti-Prx6 were detected in 25% of JDM patients, in 2% of pJIA patients, and in 0% of HC (both p=0.0005). Anti-MYL6 were detected in 16% of JDM patients, in 0% of pJIA patients (p=0.003), and in 0% of HC (p=0.008). The median plasma levels of anti-Prx6 and anti-MYL6 were higher in JDM than in pJIA (both p=0.001), and in HC (both p< 0.0001). Anti-melanoma differentiation-associated protein 5 (MDA5) were more frequent in JDM patients with anti-Prx6 (31%, P=0.04) and anti-MYL6 (40%, P=0.03). Interstitial lung disease (ILD) was associated with the presence of anti-Prx6 (31% vs. 2%, p=0.003), anti-MYL6 (30% vs. 6%, p< 0.05) and anti-MDA5 (44% vs. 4%, p=0.003). Interestingly, all ILD patients without anti-MDA5 had anti-Prx6. Higher median levels of creatinine and lower median levels of aldolase were found in the sera of JDM children with anti-Prx6 compared to in those without (P=0.006 and P=0.03, respectively). The median number of hospitalizations was higher in JDM patients with anti-MYL6 than in those without (p=0.001). Use of wheelchairs and/or assistive devices was associated with the presence of anti-MYL6 (p=0.002), including at last follow up (p=0.002). A history of cutaneous ulcers was associated with the presence of anti-MYL6 (p=0.008). Disease activity at most recent evaluation and median scores by the Steinbrocker’s functional classification were higher in JDM patients with anti-MYL6 than in those without (both p=0.01). Anti-MYL6-positive patients with JDM had received treatment with both intravenous methylprednisolone and IVIG. Further, JDM patients with anti-MYL6 had higher Myositis Damage Index severity of damage scores and Physician Global Damage Assessment than those without (both p=0.02). Lastly, the presence of anti-Prx6 and anti-MYL6 was associated with a decrease in the frequency of HLA-DPB1*04:01 [11% vs. 31%, OR 0.27 (95% CI 0.08- 0.95), p=0.04] and the presence of HLA-DRB1*11:03 (11% vs. 0%, OR not calculable, p=0.02), respectively.

Conclusion: Anti-Prx6 and anti-MYL6 in the proteome of HAEC are present in the plasma of patients with JDM. AECA may be involved in the pathophysiology of vascular injury leading to endothelial cell damage in JDM, but larger studies are required to determine their clinical utility.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-peroxiredoxin-6-and-anti-myosin-light-polypeptide-6-autoantibodies-with-interstitial-lung-disease-and-severe-disease-in-juvenile-dermatomyositis/