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

Interleukin-7 and Toll-like receptor 7 induce synergistic B cell and T cell activation.

OBJECTIVES: To investigate the potential synergy of IL-7-driven T cell-dependent and TLR7-mediated B cell activation and to assess the additive effects of monocyte/macrophages in this respect. METHODS: Isolated CD19 B cells and CD4 T cells from healthy donors were co-cultured with TLR7 agonist (TLR7A, Gardiquimod), IL-7, or their combination with or without CD14 monocytes/macrophages (T/B/mono; 1 : 1 : 0,1). Proliferation was measured using 3H-thymidine incorporation and Ki67 expression. Activation marker (CD19, HLA-DR, CD25) expression was measured by FACS analysis. Immunoglobulins were measured by ELISA and release of cytokines was measured by Luminex assay. RESULTS: TLR7-induced B cell activation was not associated with T cell activation. IL-7-induced T cell activation alone and together with TLR7A synergistically increased numbers of both proliferating (Ki67+) B cells and T cells, which was further increased in the presence of monocytes/macrophages. This was associated by up regulation of activation markers on B cells and T cells. Additive or synergistic induction of production of immunoglobulins by TLR7 and IL-7 was associated by synergistic induction of T cell cytokines (IFNγ, IL-17A, IL-22), which was only evident in the presence of monocytes/macrophages. CONCLUSIONS: IL-7-induced CD4 T cell activation and TLR7-induced B cell activation synergistically induce T helper cell cytokine and B cell immunoglobulin production, which is critically dependent on monocytes/macrophages. Our results indicate that previously described increased expression of IL-7 and TLR7 together with increased numbers of macrophages at sites of inflammation in autoimmune diseases like RA and pSS significantly contributes to enhanced lymphocyte activation

IL-7 and TLR7 synergistically increases CD4 T cell proliferation in T and B co-cultures.

<p>Representative FACS stainings for KI67⁺ CD4 T cells from unstimulated, IL-7, and TLR7/IL-7 stimulated T/B cell co-cultures in the absence or presence of monocytes/macrophages are shown (n = 5). IL-7 significantly stimulates proliferation of CD4 T cells, which is synergistically increased when combined with TLR7 stimulation (<b>A, B</b>). IL-7-induced CD4 T cell proliferation is enhanced in the presence of monocytes/macrophages, but no additive effect is observed with a combination of IL-7 and TLR7 stimulation (<b>C, D</b>).*p<0.05 and **p<0.001 indicate statistical significance compared to medium values.</p

IL-7 synergistically increases proliferation of TLR7-stimulated B cells in co-culture with CD4 T cells, which is enhanced by monocytes/macrophages.

<p>Isolated B cells co-cultured 1∶1 (5.10⁵ each) together with CD4 T cells for 6 days show an increased lymphocytic proliferation upon TLR7 or IL-7 stimulation, which is additively increased upon combined stimulation with IL-7/TLR7 (n = 8) (A). A similar, but overall enhanced effect for the total proliferation is seen when monocytes/macrophages are added to the culture (5.10⁴ B). Representative FACS stainings for KI67⁺ B cells from an unstimulated, TLR7, IL-7, and TLR7/IL-7 stimulated CD4 T/B cell co-culture -/+ monocytes/macrophages are shown as well as the average data (n = 5) (C, D). TLR7 induces a significant increase in the percentage of KI67⁺ B cells. IL-7 stimulation induces a small, but statistically significant increase in Ki67⁺ B cells. When TLR7 and IL-7 are added together a synergistic increase in proliferation is observed (C). Overall the effects are enhanced by addition of monocytes/macrophages to the T/B cell co-cultures (D). * and ** indicate a statistical significant differences of p<0.05 and p<0.01, respectively, as compared to medium values or between treatments.</p