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Background: The eosinophil is deeply associated with the pathogenesis of bronchial asthma and other allergic diseases. We recently identified a novel eosinophil-specific cell surface molecule, major facilitator super family domain containing 10 (Mfsd10). A monoclonal antibody (mAb) against Mfsd10 (M2) showed selective binding and neutralizing activities for eosinophils. However, the relative potency of the blockage of Mfsd10 and other eosinophil-specific molecules for the treatment of allergic diseases has not been evaluated. Therefore, in this study, the effects of M2 and an anti-Siglec-F mAb on antigen-immunized and antigen-specific Th2 cell-transferred murine eosinophilic inflammation models were comparatively investigated. Methods: Ovalbumin (OVA)-specific Th2 cells were differentiated from naïve CD4+ T cells of DO11.10/RAG-2−/− mice in vitro and cytokine producing activity of the Th2 cells was examined. OVA-immunized and Th2 cell- transferred BALB/c mice were treated with M2 or anti-Siglec-F and challenged with OVA. Then the number of inflammatory cells and the concentration of IL-5 in the bronchoalveolar lavage fluid (BALF) were determined. Results: Antigen-specific Th2 cells produced large amounts of IL-4, IL-5 and IL-13 but not IL-17A or IFN-γ. Administration of M2 significantly suppressed antigen-induced lung eosinophil infiltration both in OVA-immunized and Th2 cell-transferred mice. The potency as well as selectivity of M2 for down-regulating eosinophils was quite similar to that of anti-Siglec-F. Both mAbs did not affect antigen-induced IL-5 production in the lungs. Conclusions: Mfsd10 as well as Siglec-F could be an effective target to treat eosinophil-related disorders including bronchial asthma.

Natural immunoglobulin M (IgM) is reactive to autoantigens and is believed to be important for autoimmunity. Blood pentameric IgM loaded with antigens forms a large immune complex (IC) that contains various elements, including apoptosis inhibitor of macrophage (AIM). Here we demonstrate that this IgM-AIM association contributes to autoantibody production under obese conditions. In mice fed a high-fat diet, natural IgM increased through B cell TLR4 stimulation. AIM associated with IgM and protected AIM from renal excretion, increasing blood AIM levels along with the obesity-induced IgM augmentation. Meanwhile, the AIM association inhibited IgM binding to the Fcα/μ receptor on splenic follicular dendritic cells, thereby protecting the IgM IC from Fcα/μ receptor-mediated internalization. This supported IgM-dependent autoantigen presentation to B cells, stimulating IgG autoantibody production. Accordingly, in obese AIM-deficient (AIM−/−) mice, the increase of multiple IgG autoantibodies observed in obese wild-type mice was abrogated. Thus, the AIM-IgM association plays a critical role in the obesity-associated autoimmune process.

Background: Different energy sources of balloon-based ablation for pulmonary vein isolation cause different kinds of endothelial damage and coagulation responses associated with thromboembolic risk. Objectives: The study sought to compare the impact of different balloon-based ablation, cryoballoon ablation (CBA) and laser balloon ablation (LBA), on coagulation/fibrinolysis biomarkers and silent cerebral events (SCEs) in paroxysmal atrial fibrillation. Methods: Paroxysmal atrial fibrillation patients who underwent pulmonary vein isolation using either CBA (n = 52) or LBA (n = 53) without radiofrequency touch-up ablation were eligible. Time course (day 0 [before ablation], day 1, day 2, and day 28) of myocardial enzymes and inflammatory and coagulation/fibrinolysis biomarkers was evaluated during the perioperative period. Brain magnetic resonance imaging was performed within 2 days after the procedure to evaluate SCEs. Results: There was no difference in patient characteristics between CBA and LBA.CBA had greater myocardial injury (troponin I and creatine kinase-MB) and lower inflammatory reaction (white blood cell count and neutrophil/lymphocyte ratio) than LBA. The coagulation biomarkers maximally increased by day 2 and then decreased in both groups. In day 28, the serum prothrombin fragment 1+2 and D-dimer levels in LBA were significantly higher than the values in CBA. The fibrinolysis biomarker (plasmin-α2 plasmin inhibitor complex) did not increase after the procedure in either group. The incidence of SCEs was comparable between CBA and LBA (11% vs 15%; P = .591). No thromboembolic event was observed. Conclusion: CBA and LBA had different effects on myocardial injury, inflammatory reaction, and coagulation activity but did not affect the incidence of thromboembolic events. LBA had significantly higher coagulation activity in day 28 and may require more careful postprocedural anticoagulation than CBA.

Background: Since warfarin is primarily bound to serum albumin, hypoalbuminemia is likely to increase the free fraction of warfarin and to increase the risk of bleeding. We prospectively evaluated the impact of serum albumin levels (ALB) on international normalized ratio of prothrombin time (PT-INR) control and hemorrhagic events in atrial fibrillation (AF) patients treated with warfarin. Methods: Seven hundred fifty-five non-valvular AF patients on warfarin were enrolled. PT-INR control and major bleeding events (MB, International Society on Thrombosis and Haemostasis) were prospectively followed and were related to ALB at enrollment. Results: Twenty-seven patients developed MB during 1-year follow-up. In univariate/multivariate analyses, ALB (OR = 0.49, 95% CI 0.26–0.99, p = 0.04) and hemoglobin levels (OR = 0.78, 95% CI 0.65–0.92, p = 3.0 (ρ = −0.15, p