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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., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Antiplatelet-antibody-producing B cells play a key role in immune thrombocytopenia (ITP) pathogenesis; however, little is known about T-cell dysregulations that support B-cell differentiation. During the past decade, T follicular helper cells (TFHs) have been characterized as the main T-cell subset within secondary lymphoid organs that promotes B-cell differentiation leading to antibody class-switch recombination and secretion. Herein, we characterized TFHs within the spleen of 8 controls and 13 ITP patients. We show that human splenic TFHs are the main producers of interleukin (IL)-21, express CD40 ligand (CD154), and are located within the germinal center of secondary follicles. Compared with controls, splenic TFH frequency is higher in ITP patients and correlates with germinal center and plasma cell percentages that are also increased. In vitro, IL-21 stimulation combined with an anti-CD40 agonist antibody led to the differentiation of splenic B cells into plasma cells and to the secretion of antiplatelet antibodies in ITP patients. Overall, these results point out the involvement of TFH in ITP pathophysiology and the potential interest of IL-21 and CD40 as therapeutic targets in ITP., (© 2014 by The American Society of Hematology.)

Background: Polarization of macrophages by specific micro-environmental conditions impacts upon their function following subsequent activation. This study aimed to systematically validate robust phenotypic markers for in vitro polarized human macrophages in order to facilitate the study of macrophage subsets in vivo., Methods: Human peripheral blood monocytes were polarized in vitro with IFN-γ, IL-4, or IL-10. Similar experiments were performed with TNF, IL-13, dexamethasone, M-CSF and GM-CSF as polarizing stimuli. Phenotypic markers were assessed by flow cytometry and qPCR., Results: IFN-γ polarized macrophages (MΦ(IFN-γ)) specifically enhanced membrane expression of CD80 and CD64, IL-4 polarized macrophages (MΦ(IL-4)) mainly upregulated CD200R and CD206, and downregulated CD14 levels, and IL-10 polarized macrophages (MΦ(IL-10)) selectively induced CD163, CD16, and CD32. The expression profiles of the most specific markers were confirmed by qPCR, dose-response experiments, and the use of alternative polarizing factors for each macrophage subset (TNF, IL-13, and dexamethasone, respectively). GM-CSF polarized macrophages (MΦ(GM-CSF)) upregulated CD80 but not CD64 expression, showing a partial phenotypic similarity with MΦ(IFN-γ), and also upregulated the expression of the alternative activation marker CD206. M-CSF polarized macrophages (MΦ(M-CSF)) not only expressed increased levels of CD163 and CD16, resembling MΦ(IL-10,) but also displayed high levels of CD64. The phenotype of MΦ(M-CSF) could be further modulated by additional polarization with IFN-γ, IL-4, or IL-10, whereas MΦ(GM-CSF) showed less phenotypic plasticity., Conclusion: This study validated CD80 as the most robust phenotypic marker for human MΦ(IFN-γ), whereas CD200R was upregulated and CD14 was specifically downregulated on MΦ(IL-4). CD163 and CD16 were found to be specific markers for MΦ(IL-10). The GM-CSF/M-CSF differentiation model showed only a partial phenotypic similarity with the IFN-γ/IL-4/IL-10 induced polarization., (Copyright © 2011. Published by Elsevier B.V.)

Immune activation of fibrosis likely has a crucial role in the pathogenesis of systemic sclerosis (SSc). The aim of this study was to better understand the innate immune regulation and associated IFN- and transforming growth factor-β (TGFβ)-responsive gene expression in SSc skin and dermal fibroblasts, in particular the effect of different Toll-like receptor (TLR) ligands. To better understand the relationship between inflammation and fibrosis in vivo, we developed a murine model for chronic innate immune stimulation. We found that expression of both IFN- and TGFβ-responsive genes is increased in SSc skin and SSc fibroblasts when stimulated by TLR ligands. In contrast, cutaneous lupus skin showed much more highly upregulated IFN-responsive and much less highly upregulated TGFβ-responsive gene expression. Of the TLRs ligands tested, the TLR3 ligand, polyinosinic/polycytidylic acid (Poly(I:C)), most highly increased fibroblast expression of both IFN- and TGFβ-responsive genes as well as TLR3. Chronic subcutaneous immune stimulation by Poly(I:C) stimulated inflammation, and IFN- and TGFβ-responsive gene expression. However, in this model, type I IFNs had no apparent role in regulating TGFβ activity in the skin. These results suggest that TLR agonists may be important stimuli of dermal fibrosis, which is potentially mediated by TLR3 or other innate immune receptors.

CXCL16 acts as a scavenger receptor for oxLDL in its membrane-bound form and induces migration of activated T cells in its soluble form. Due to these properties, CXCL16 has been suggested to play a role in both atherosclerosis and rheumatoid arthritis (RA). Our aim was to evaluate the contribution of soluble CXCL16 to the scavenging of oxLDL and its potential as a marker for cardiovascular disease (CVD) in patients with RA. We found that circulating CXCL16 was not correlated with plasma oxLDL or ApoB and was not related to the presence of CVD in RA patients. Moreover, CXCL16 did not bind and scavenge oxLDL in an in vitro setting. These data suggest that binding of oxLDL by soluble CXCL16 does not play a role in atherosclerosis and, although confirmation in larger studies is needed, that circulating CXCL16 is not related to the presence of CVD in patients with RA.