General autoimmunity

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Retained Inflammatory Signaling in Peripheral Blood Mononuclear Cells from Children with Quiescent Juvenile Dermatomyositis and Active Psoriasis

Friday, June 16
6:15 PM - 7:30 PM

Background: The Cure JM Registry/Repository follows 492 JDM and sequentially collects clinical information and biological samples, including peripheral blood mononuclear cells (PBMCs). Approximately 8% of patients later develop a secondary autoimmune disease, most commonly psoriasis (~2%). This study compared the immunological pattern for PBMC RNASeq during active JDM with the same child's PBMC pattern during Psoriasis and to matched controls.


Methods: We identified JDM patients (n=5) with stored PBMCs from the time of active JDM and PBMCs obtained after the onset of Psoriasis, approximately 10 years later, as well as 2 sets of controls, age/sex matched to the PBMC samples (n=5). The PBMC transcriptome was assessed using stranded RNA sequencing.


Results: Using a paired-sample analysis, the JDM-only PBMCs were essentially the same as the PBMCs from active psoriasis, with only a single differentially expressed gene. In contrast, the JDM samples, compared to controls, exhibited numerous genes significantly increased fold-change (FC) greater than 2 (n=115) and decreased less than -2 (n=9), encompassing inflammatory genes, such as JUN (4.3 FC; p < 0.0001), MAP3K8 (FC 3.0, p < 0.01), and lipid processing, OLR1 (FC 33.1, p < 0.01). The genes significantly increased at least 2-fold were enriched for the NK-kappa B and TNF signaling pathways.


Conclusions: As expected, PBMCs from symptomatic JDM displayed increased immunological activity compared to controls, with enrichment of several key pathways. However, this signature had not significantly altered a decade later, when they developed psoriasis, suggesting a shared genetic liability for both JDM and Psoriasis, and, perhaps, other autoimmune diseases.

Lauren M. Pachman

Professor
Northwestern University Feinberg School of Medicine, Stanley Manne Children’s Research Center, Ann and Robert H. Lurie Children’s Hospital

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    Li Cao

    Washington University School of Medicine, Department of Internal Medicine, Division of Rheumatology

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      Gabrielle A. Morgan

      Data Manager
      Stanley Manne Children's Research Institute

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        Brienne Lubor

        Ann & Robert H. Lurie Children's Hospital of Chicago

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          Dong Xu

          Ann & Robert H. Lurie Children's Hospital of Chicago

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            Chiang-Ching Huang

            Joseph J. Zilber School of Public Health, University of Wisconsin, Milwaukee

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              Elisha Roberson

              Washington University School of Medicine, Department of Internal Medicine, Division of Rheumatology

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                Retained Inflammatory Signaling in Peripheral Blood Mononuclear Cells from Children with Quiescent Juvenile Dermatomyositis and Active Psoriasis



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