Autoimmune rheumatologic diseases

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A Role for Ifnb in Systemic Lupus Erythematosus (sle) Is Predicted by analysis of Gene Expression Data Sets

Thursday, June 15
5:45 PM - 7:00 PM

SLE patients overexpress interferon signature genes (ISG), but the major interferon (IFN) involved in lupus pathogenesis remains uncertain. To address this issue, Gene Set Variation Analysis (GSVA) was carried out on hundreds of SLE and control microarrays from B cell, T cell, myeloid cell, PBMC, WB, kidney, skin and synovium.  The GSVA reference datasets used were the three previously reported IFN-Modules (IFN-M, Chiche, 2014) and microarray data from in vitro treatment of healthy human PBMC with IFNA2, IFNB1, IFNW, IFNG, IL12 and TNF (Waddel, 2010).GSVA using the in vitro PBMC data showed similar or better separation of SLE patients from controls than the IFN-M, and additionally identified patients with TNF and IL12 signatures lacking IFN signatures.  Z score calculations to determine the most likely upstream regulator predicted IFNB1 and IFNW as the major IFNs inducing the IGS for all SLE tissues. Confirmation of the strong IFNB1 signal was carried out using published microarray data of the IFNB1 signature in Multiple Sclerosis (MS) Patients (MS IFNB1; Nickles, 2013).  The MS IFNB1 had superior overlap to SLE datasets compared to both IFN-M and the in vitro PBMC IFN Signature.  Z score calculations using the MS IFNB1 signature showed high Z scores for all active SLE cells and tissues.  The data indicate that IFNB and IFNW are the most likely IFN family member upstream regulators accounting for the ISG in active SLE cells and tissues and suggest that IFNB1 and IFNW may represent novel therapeutic interventions for SLE.

Michelle D. Catalina

AMPEL BioSolutions, LLC

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    Prathyusha Bachali

    Ampel Biosolutions, LLC

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      Sushma Madamanchi

      Ampel Biosolutions, LLC

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        Amrie C. Grammer

        COO & CSO
        Ampel Biosolutions, LLC

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          Peter E. Lipsky

          CEO & CMO
          Ampel Biosolutions, LLC

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            A Role for Ifnb in Systemic Lupus Erythematosus (sle) Is Predicted by analysis of Gene Expression Data Sets



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