microRNA downregulation in plasmacytoid dendritic cells in interferon-positive systemic lupus erythematosus and antiphospholipid syndrome

To investigate miRNA expression in relation to transcriptomic changes in plasmacytoid dendritic cells (pDCs) in SLE and APS. pDCs are major producers of IFN\u3b1 in SLE and APS, and miRNAs are emerging as regulators of pDC activation

RNA sequencing to predict response to TNF-\u3b1 inhibitors reveals possible mechanism for nonresponse in smokers

Several studies have employed microarray-based profiling to predict response to tumor necrosis factor-alpha inhibitors (TNFi) in rheumatoid arthritis (RA); yet efforts to validate these targets have failed to show predictive abilities acceptable for clinical practice

Galectin-9 is an easy to measure biomarker for the interferon signature in systemic lupus erythematosus and antiphospholipid syndrome

The interferon (IFN) signature is related to disease activity and vascular disease in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) and represents a promising therapeutic target. Quantification of the IFN signature is currently performed by gene expression analysis, limiting its current applicability in clinical practice. Therefore, the objective of this study was to establish an easy to measure biomarker for the IFN signature

Delineating the deranged immune system in the antiphospholipid syndrome

The antiphospholipid syndrome (APS) is a systemic autoimmune disease that is characterized serologically by the presence of antiphospholipid antibodies (aPL) and clinically by vascular thrombosis and obstetric complications. The protein β2 glycoprotein I (β2GPI) is identified as the most important autoantigen in this syndrome. Activation of endothelial cells, thrombocytes and placental tissue by anti-β2GPI antibodies relates to the clinical manifestations of APS. This review describes genetic and environmental factors in relation to APS and summarizes the current knowledge on abnormalities in components of both the innate and adaptive immune system in APS. The role of dendritic cells, T-cells, B-cells, monocytes, neutrophils and NK-cells as well as the complement system in APS are discussed. Several gaps in our knowledge on the pathophysiology of APS are identified and a plea is made for future extensive immune cell profiling by a systems medicine approach in order to better unravel the pathogenesis of APS, to gain more insight in the role of the immune system in APS as well as having the potential to reveal biomarkers or novel therapeutic targets

Serum cytokine patterns in immunoglobulin m monoclonal gammopathy-associated polyneuropathy

Introduction: Polyneuropathy with immunoglobulin M monoclonal gammopathy (IgM-PNP) is associated with the presence of IgM antibodies against nerve constituents such as myelin associated glycoprotein (MAG) and gangliosides. Methods: To test whether B-cell-stimulating cytokines are increased in IgM-PNP, we measured serum concentrations of 11 cytokines in 81 patients with IgM-PNP and 113 controls. Results: Median interleukin (IL)-6 concentrations were higher in patients with IgM-PNP, and median IL-10 concentrations were higher in the subgroup with anti-MAG IgM antibodies. These serum concentrations were not increased in 110 patients with multifocal motor neuropathy. Discussion: Median IL-6 and IL-10 serum concentrations differ between patients with anti-MAG neuropathy and other patients with IgM-PNP compared with healthy and neuropathy controls. These differences may indicate differences in immune-mediated disease mechanisms. Muscle Nerve 59:694–698, 2019

Low-molecular-weight heparin and aspirin use in relation to pregnancy outcome in women with systemic lupus erythematosus and antiphospholipid syndrome: A cohort study

OBJECTIVE: To relate anticoagulant use to pregnancy complications in women with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). METHODS: All ongoing pregnancies, 184, in two Dutch tertiary centers between 2000 and 2015. RESULTS: LMWH and aspirin was prescribed in 15/109 SLE women without antiphospholipid antibodies (aPL), 5/14 with aPL, 11/13 with APS, 45/48 with primary APS. Main complications in the four treatment groups (no anticoagulant treatment, aspirin, LMWH, aspirin and LMWH) included hypertensive disorders of pregnancy (9.4%, 23.3%, 50%, 18.4%, respectively, p = 0.12) and preterm birth (16.7%, 34.3%, 75%, 36.8%, respectively, p < 0.001). CONCLUSION: Maternal and perinatal complications occurred frequently, despite LMWH and aspirin use