[Long-lasting souvenir from Cameroon - Persistent, massive hypereosinophilia in amicrofilaremic infection with Loa loa]. / Langlebiges Souvenir aus Kamerun ­ persistierende, massive Hypereosinophilie bei amikrofilarämischer Infektion mit Loa loa.

INTRODUCTION: Diagnosis of a polysymptomatic, rare parasitosis requires collaboration of internal specialists, tropical disease specialists, parasitologists and dermatologists. HISTORY: The course of disease is shown in a 66-year-old woman who regularly travels to Cameroon and presented with remarkable hypereosinophilia and pruritus with urticarial swellings. FINDINGS AND DIAGNOSIS: Using interdisciplinary diagnostics based on travel history, symptoms and laboratory results an occult amicrofilaraemic Loa loa infection with immunological hyperreaction to the parasite antigen, reactive hypereosinophilia and high antibody titers was diagnosed. THERAPY AND COURSE: Anthelmintic therapy was inducted with ivermectin and diethylcarbamazine. Treatment with ivermectin alone resulted in a prompt regression of symptoms and decrease of eosinophil levels and antibody titers. CONCLUSIONS: Parasitic diseases like L. loa infections are extremely rare in Europe but should be considered as differential diagnosis at an early stage when patients present with appropriate travel history and clinical findings. There is a lack of standardized therapy and follow-up recommendations. A precise recording of all new diagnoses with therapy progress/response should be established in an international registry.

The Role of Immune Checkpoints after Cellular Therapy.

Cellular therapies utilize the powerful force of the human immune system to target malignant cells. Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the most established cellular therapy, but chimeric antigen receptor (CAR) T cell therapies have gained attention in recent years. While in allo-HCT an entirely novel allogeneic immune system facilitates a so-called Graft-versus-tumor, respectively, Graft-versus-leukemia (GvT/GvL) effect against high-risk hematologic malignancies, in CAR T cell therapies genetically modified autologous T cells specifically attack target molecules on malignant cells. These therapies have achieved high success rates, offering potential cures in otherwise detrimental diseases. However, relapse after cellular therapy remains a serious clinical obstacle. Checkpoint Inhibition (CI), which was recently designated as breakthrough in cancer treatment and consequently awarded with the Nobel prize in 2018, is a different way to increase anti-tumor immunity. Here, inhibitory immune checkpoints are blocked on immune cells in order to restore the immunological force against malignant diseases. Disease relapse after CAR T cell therapy or allo-HCT has been linked to up-regulation of immune checkpoints that render cancer cells resistant to the cell-mediated anti-cancer immune effects. Thus, enhancing immune cell function after cellular therapies using CI is an important treatment option that might re-activate the anti-cancer effect upon cell therapy. In this review, we will summarize current data on this topic with the focus on immune checkpoints after cellular therapy for malignant diseases and balance efficacy versus potential side effects.

Loss of Biglycan Enhances Thrombin Generation in Apolipoprotein E-Deficient Mice: Implications for Inflammation and Atherosclerosis.

OBJECTIVE: Thrombin signaling promotes atherosclerosis by initiating inflammatory events indirectly through platelet activation and directly via protease-activated receptors. Therefore, endogenous thrombin inhibitors may be relevant modulators of atheroprogression and cardiovascular risk. In addition, endogenous thrombin inhibitors may affect the response to non-vitamin K-dependent oral anticoagulants. Here, the question was addressed whether the small leucine-rich proteoglycan biglycan acts as an endogenous thrombin inhibitor in atherosclerosis through activation of heparin cofactor II. APPROACH AND RESULTS: Biglycan concentrations were elevated in the plasma of patients with acute coronary syndrome and in male Apolipoprotein E-deficient (ApoE(-/-)) mice. Biglycan was detected in the glycocalyx of capillaries and the subendothelial matrix of arterioles of ApoE(-/-) mice and in atherosclerotic plaques. Thereby a vascular compartment is provided that may mediate the endothelial and subendothelial activation of heparin cofactor II through biglycan. ApoE and Bgn double-deficient (ApoE(-/-)/Bgn(-/0)) mice showed higher activity of circulating thrombin, increased platelet activation and platelet adhesion in vivo, supporting a role of biglycan in balancing thrombin activity. Furthermore, concentrations of circulating cytokines and aortic macrophage content were elevated in ApoE(-/-)/Bgn(-/0) mice, suggesting a proinflammatory phenotype. Elevated platelet activation and macrophage accumulation were reversed by treating ApoE(-/-)/Bgn(-/0) mice with the thrombin inhibitor argatroban. Ultimately, ApoE(-/-)/Bgn(-/0) mice developed aggravated atherosclerosis. CONCLUSIONS: The present results indicate that biglycan plays a previously unappreciated protective role during the progression of atherosclerosis by inhibiting thrombin activity, platelet activation, and finally macrophage-mediated plaque inflammation.