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The establishment of an “interferon (IFN) signature” to subset SLE patients on disease severity has led to therapeutics targeting IFNα. Here, we investigate IFN signaling in SLE using multiplexed protein arrays and single cell cytometry by time of flight (CyTOF). First, the IFN signature for SLE patients (n=81) from the Stanford Lupus Registry is determined using fluidigm qPCR measuring 44 previously determined IFN-inducible transcripts. IFN-high (IFN-H) patients have increased SLE criteria and renal/CNS/immunologic involvement, and increased autoantibody reactivity against spliceosome-associated antigens. CyTOF analysis is performed on non-stimulated and stimulated (IFNα, IFNγ, IL-21) PBMCs from SLE patients (n=25) and HCs (n=9) in a panel identifying changes in phosphorylation of intracellular signaling proteins (pTOF). Another panel is utilized to detect changes in intracellular cytokine (ICTOF) production in non-stimulated and stimulated (PMA/ionomycin) PBMCs from SLE patients (n=31) and HCs (n=17). Bioinformatic analysis by MetaCyto and OMIQ reveal phenotypic changes in immune cell subsets between IFN-H and IFN-low (IFN-L) patients. Most notably, IFN-H patients exhibit increased STAT1/3/5 phosphorylation downstream of cytokine stimulation and increased phosphorylation of non-canonical STAT proteins. These results suggest that IFN signaling in SLE modulates STAT phosphorylation, potentially uncovering possible targets for future therapeutic approaches.

BackgroundThe effect of pregnancy on Dermatomyositis (DM) disease activity and on maternal and fetal outcomes in patients with DM is unclear1,2.ObjectivesEvaluate disease activity and pregnancy outcomes complicated by maternal dermatomyositis.MethodsA total of 10 patients with 21 pregnancies from a cohort of 438 DM patients of child-bearing potential, diagnosed between 2006 and 2015 from two centers, were eligible for interview with a specific questionnaire regarding pregnancy and fetal outcomes.ResultsWeakness, rash and arthritis were the most common clinical symptoms that improved during pregnancy in affected patients (Figure 1). In 16 out of 18 pregnancies, patients experienced weakness. Weakness improved during 13 pregnancies (81.3%), stayed the same during 2 pregnancies (12.5%), and worsened during one (6.3%). All 10 patients experienced cutaneous rash during all 18 pregnancies carried to live birth. Cutaneous rash improved during 13 pregnancies (72.2%), remain unchanged during 3 (16.7%), and worsened during 2 (11.1%). Five patients experienced arthralgias or arthritis in a total of 11 pregnancies. Symptoms improved during 10 of these pregnancies (91%) and worsened during one (9%).There were no cases of interstitial lung disease, cancer or antiphospholipid antibody syndrome among the 10 patients studied. One patient suffered from pre-eclampsia while diagnosed with DM. 3 total pregnancy losses: two early miscarriages (<10 weeks gestation) one therapeutic abortion for an ectopic pregnancy. 3 neonates out of 18 live births went to the NICU after delivery – reasons for transfer: meconium aspiration; apnea and pre-term birth.ConclusionsPregnancy does not appear to carry a worse prognosis for DM patients and all but one of our patients experienced improvement in clinical symptoms during pregnancy.ReferencesIago PF et al. Pregnancy in adult-onset idiopathic inflammatory myopathy: Report from a cohort of myositis patients from a single center. Semin Arthritis Rheum, 2014. 44 (2):p.234–240.Oddis, C.V., et al., Incidence of polymyositis-dermatomyositis: a 20-year study of hospital diagnosed cases in Allegheny County, PA 1963–1982. J Rheumatol, 1990. 17(10): p. 1329–34.Disclosure of InterestNone declared

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