What is the role of complement in bystander hemolysis? Old concept, new insights.

INTRODUCTION: Bystander hemolysis occurs when antigen-negative red blood cells (RBCs) are lysed by the complement system. Many clinical entities including passenger lymphocyte syndrome, hyperhemolysis following blood transfusion, and paroxysmal nocturnal hemoglobinuria are complicated by bystander hemolysis. AREAS COVERED: The review provides data about the role of the complement system in the pathogenesis of bystander hemolysis. Moreover, future perspectives on the understanding and management of this syndrome are described. EXPERT OPINION: Complement system can be activated via classical, alternative, and lectin pathways. Classical pathway activation is mediated by antigen-antibody (autoantibodies and alloantibodies against autologous RBCs, infectious agents) complexes. Alternative pathway initiation is triggered by heme, RBC microvesicles, and endothelial injury that is a result of intravascular hemolysis. Thus, C5b is formed, binds with C6-C9 compomers, and MAC (C5b-9) is formulated in bystander RBCs membranes, leading to cell lysis. Intravascular hemolysis, results in activation of the alternative pathway, establishing a vicious cycle between complement activation and bystander hemolysis. C5 inhibitors have been used effectively in patients with hyperhemolysis syndrome and other entities characterized by bystander hemolysis.

Risk Factors, Prevalence, and Outcomes of Invasive Fungal Disease Post Hematopoietic Cell Transplantation and Cellular Therapies: A Retrospective Monocenter Real-Life Analysis.

(1) Background: Autologous, allogeneic hematopoietic cell transplantation (HCT) and other cellular therapies, including CAR T cell and gene therapy, constitute a cornerstone in the management of various benign and malignant hematological disorders. Invasive fungal infections (IFD) remain a significant cause of morbidity and mortality in HCT recipients. Therefore, we investigated the prevalence and risk factors of IFD following HCT and other cellular therapies in an era of novel antifungal prophylaxis. (2) Methods: In this study, we retrospectively enrolled adult HCT recipients who were treated at our JACIE-accredited center according to standard operating procedures over the last decade (2013-2022). (3) Results: 950 patients who received cellular therapies were studied. None of the 19 CAR T cell and neither of the two gene therapy recipients developed IFD whereas 3/456 autologous HCT recipients who suffered from primary refractory/relapsed lymphomas presented with probable IFD. Overall, 11 patients who received allogeneic HCT experienced probable IFD, possible IFD was found in 31/473, and IFD was proven in 10/473. A second IFD episode was present in three patients. Four-year OS was significantly lower in proven compared to probable IFD (p = 0.041) and was independently associated with HCT-CI (p = 0.040) and chronic GVHD (p = 0.045). (4) Conclusions: In this real-world cohort, the prevalence of proven and probable IFD in an era of novel antifungal prophylaxis was found to be relatively low. However, IFDs were associated with poor outcomes for patients who received allogeneic HCT.

CNS Border-Associated Macrophages: Ontogeny and Potential Implication in Disease.

Being immune privileged, the central nervous system (CNS) is constituted by unique parenchymal and non-parenchymal tissue-resident macrophages, namely, microglia and border-associated macrophages (BAMs), respectively. BAMs are found in the choroid plexus, meningeal and perivascular spaces, playing critical roles in maintaining CNS homeostasis while being phenotypically and functionally distinct from microglial cells. Although the ontogeny of microglia has been largely determined, BAMs need comparable scrutiny as they have been recently discovered and have not been thoroughly explored. Newly developed techniques have transformed our understanding of BAMs, revealing their cellular heterogeneity and diversity. Recent data showed that BAMs also originate from yolk sac progenitors instead of bone marrow-derived monocytes, highlighting the absolute need to further investigate their repopulation pattern in adult CNS. Shedding light on the molecular cues and drivers orchestrating BAM generation is essential for delineating their cellular identity. BAMs are receiving more attention since they are gradually incorporated into neurodegenerative and neuroinflammatory disease evaluations. The present review provides insights towards the current understanding regarding the ontogeny of BAMs and their involvement in CNS diseases, paving their way into targeted therapeutic strategies and precision medicine.