Date: Monday, October 22, 2018
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: JDM is a complex heterogeneous autoimmune disease. To define biomarkers and better understand JDM pathogenesis, aptamer-based proteomic technology was used to mine the serum proteome in a well-characterized JDM cohort.
Methods: Sera from 41 JDM patients (prevalent cases on variable treatment) were compared with 28 age- and gender-matched healthy controls (HC). Broad proteomic analysis of 1306 targets with a slow off-rate modified aptamer-based assay (SomaLogic, CO) generated simultaneous quantitative serum levels. Internal discovery/validation was done with 2 independently-analyzed groups (Group 1: JDM 27, HC 19; Group 2: JDM 14, HC 9) assessed for Mann Whitney U FDR corrected p values of <0.10 (JDM vs. HC) common to both groups with expression ratio of >1.3. Significant protein levels were positively correlated by Spearman rank with Physician Global Activity (PGA) and Physician Global Damage (PGD) by visual analog scale (VAS), Manual Muscle Testing (MMT8), Childhood Muscle Assessment Scale (CMAS), Childhood Health Assessment Questionnaire (CHAQ), and disease activity by VAS specific to skin and muscle using the Myositis Disease Activity Assessment Tool (MDAAT) selecting for p values <0.05. Proteins were also analyzed by Ingenuity Pathway Analysis (Qiagen, CA) and Gene Ontology (GO) (Ashburner et al, 2000) biologic processes to identify pathway clusters.
Results: Fifty-nine proteins met significance criteria in both groups of JDM versus HC sera. Of those, 20/59 had significant correlation with 1 to 4 clinical measures (Table 1). Nine proteins correlated with PGA (rs = 0.31-0.37), most commonly associated with acute phase response (APR) and endothelial activation/ adhesion (Endo). Three proteins uniquely correlated with PGD (rs =0.33-0.54), and associated with Endo, IFN, and proteolysis/remodeling (Remodeling) pathway clusters. Four proteins correlated with skin VAS (rs =0.37-0.41); most associated with IFN and Th1 pathway clusters, with 1 unique to skin and 2 overlapped with muscle VAS. Nine proteins correlated with CHAQ and 4 proteins with muscle VAS (3 overlapping with CHAQ and 1 unique to muscle VAS); overall most associated with Endo and IFN (rs =0.35-0.53). None significantly correlated with MMT or CMAS.
Conclusion: Broad quantitative proteomic analysis identified some novel serum markers that point to key differentiating pathway clusters in JDM versus HC which may provide insights into JDM pathogenesis. Moderate correlation was observed between top proteins and clinical measures, including some distinct markers for skin versus muscle activity, and for PGD. These proteins emphasize pathway clusters including APR, Endo, IFN, Th1, and Remodeling, that may be important to distinct aspects of JDM features and outcomes.
This research was supported by the Cure JM Foundation and the Intramural Research Program of the NIH, NIEHS, NHLBI, NIAID, NIAMS, CC.
To cite this abstract in AMA style:Kim H, Biancotto A, Cheung F, O'Hanlon TP, Huang Y, Miller FW, Goldbach-Mansky R, Rider LG. Proteomic Discovery Analysis Identifies Unique Proteins and Pathways Correlating with Different Clinical Activity and Damage Measures in Juvenile Dermatomyositis (JDM) [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/proteomic-discovery-analysis-identifies-unique-proteins-and-pathways-correlating-with-different-clinical-activity-and-damage-measures-in-juvenile-dermatomyositis-jdm/. Accessed August 15, 2020.
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