AbstractRecent studies have highlighted the importance of microglia as key immunomodulators in a variety of neuropsychiatric diseases. Postmortem brain analysis and positron emission tomography are representative research approaches to assess microglial activation in human patients and this research has revealed microglial activation in the brains of patients with various neuropsychiatric disorders. However, only limited aspects of microglial activation can be assessed with these methods. To overcome the technical and ethical limitations of collecting human‐derived microglia in brain biopsies, we first developed a method to generate directly induced microglia‐like (iMG) cells from fresh human peripheral blood monocytes in 2014. These iMG cells can be used to perform dynamic morphological and molecular analyses regarding phagocytic capacity and cytokine release following stress stimulation at the cellular level. Patient‐derived iMG cells can potentially serve as an important surrogate marker for estimating microglial activation in the human brain, and may provide previously unknown insights into the dynamic pathophysiology of microglia in patients with neuropsychiatric disorders. Thus, the iMG‐based technology could be used as a valuable reverse translational tool and provide new insights into the dynamic molecular pathophysiology of microglia in a wide variety of psychiatric and physical disorders.

AbstractBlood–tissue barriers play crucial roles in specialized tissues such as the central nervous system (CNS), eye, testis, and placenta. Tissue‐resident macrophages in these tissues are indispensable for maintaining tissue homeostasis and responding to pathological conditions. Recent advances in high‐throughput and high‐dimensional single‐cell analysis techniques, coupled with fate‐mapping tools, have revealed a remarkable diversity of tissue‐resident macrophages at the blood–tissue barrier. However, while comprehensive expression profiling has revealed the heterogeneity of macrophages within individual tissues, the commonalities of macrophages across anatomically similar structures like blood–tissue barriers remain poorly understood. This review focuses on the diversity and functional specialization of macrophages in tissues with blood–tissue barriers, highlighting recent insights into their anatomical distribution, developmental origins, phenotypic characteristics, and roles in maintaining tissue homeostasis. These findings may deepen our understanding of macrophage adaptation mechanisms in tissues with blood–tissue barriers, potentially leading to improved therapies for related disorders. Furthermore, examining the similarities and differences of macrophages across tissues may elucidate the molecular underpinnings of tissue‐specific adaptation mechanisms and functional specialization.

AbstractObjectivesReports of real‐world data concerning chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are limited in Japan. This study aimed to investigate the diagnostic testing and treatment performed in patients diagnosed with CIDP in Japan.MethodsUsing a Japanese commercial medical information database, we analyzed diagnostic tests, differential diseases, and treatments for patients with a diagnosis code for CIDP between April 13, 2008 and August 31, 2018.ResultsOf the 4564 patients with a diagnosis code for CIDP, 1658 patients were confirmed as newly assigned with the diagnosis code during the study period. Diagnostic tests performed before assignment of the diagnosis code for CIDP included nerve conduction studies in 48.1%, magnetic resonance imaging in 40.5%, and cerebrospinal fluid tests in 38.4%. Other diseases with codes that were assigned at the time of the CIDP diagnosis included Guillain–Barré syndrome in 8.1%, Sjögren syndrome in 4.4%, and systemic lupus erythematosus in 3.7%. Initial treatments performed after the assignment of the new diagnosis code for CIDP were intravenous immunoglobulin (IVIg) in 54.3%, corticosteroids (CS) in 45.4%, and plasmapheresis in 2.3%. The event‐free survival rates for predefined specific safety‐related events at 1000 d were 90.0% for any event in patients receiving IVIg monotherapy and 71.7% for any event in patients receiving CS monotherapy.ConclusionDiagnostic testing and treatment performed in clinical practice was shown through the analysis of real‐world data of Japanese patients with a diagnosis code for CIDP. These findings might contribute to developments in clinical practice for Japanese CIDP patients.

AbstractIntracranial aneurysms (IAs) may afflict up to 5% of the general population, or up to 15 million individuals in the US. The two forms of IAs that can be recognized by their shape are saccular and nonsaccular IAs, with uncommon aneurysm types, fusiform and dissecting aneurysms, comprising 13% of nonsaccular IAs. Conceivably, among the various risk factors for IA development, vessel wall inflammation represents a major cause. Accordingly, IAs may not necessarily be the result of passive widening of vessel wall structures, but may also be the result of inflammation and tissue degeneration. Thus, flow‐induced vascular remodeling during IA pathogenesis may reflect immune cell infiltration and consequent release of proinflammatory cytokine, chemokine, and matrix metalloproteinase that contribute to vessel wall degeneration and weakening. Thus, infiltrating neutrophils, macrophages, T‐lymphocytes and complement factors, and the resulting immune microenvironment may be pertinent in IA pathogenesis.

AbstractObjectivesA variety of myositis‐specific autoantibodies have been identified in sera from patients with idiopathic inflammatory myopathies, and they play a crucial role in tailoring personalized disease management. In particular, autoantibodies against 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR) are now recognized as a key tool for diagnosing immune‐mediated necrotizing myopathy. The current gold standard for detecting anti‐HMGCR autoantibodies involves immunoprecipitation (IP) using radiolabeled proteins from cell extracts or purified proteins produced by in vitro transcription/translation (IVTT). Unfortunately, this radioisotope labeling is technically intricate and not suitable for routine laboratory use. To address this, we developed a novel assay called “Bio‐IVTT‐IP” for detecting anti‐HMGCR autoantibodies, which uses a nonradioactive biotinylated recombinant HMGCR protein produced by IVTT.MethodsWe collected 14 clinical specimens containing anti‐HMGCR autoantibodies from patients with immune‐mediated necrotizing myopathy, which were validated using the gold standard IP assay, and a set of 35 control samples from patients with other autoimmune diseases, such as systemic lupus erythematosus.ResultsThe Bio‐IVTT‐IP assay successfully identified 14 clinical samples positive for anti‐HMGCR. We confirmed that the performance of the Bio‐IVTT‐IP assay was completely consistent with that of the gold standard IP assay using radiolabeled proteins. Notably, no immunoprecipitates were found in control samples from patients with other autoimmune diseases.ConclusionsThese findings show that the Bio‐IVTT‐IP assay can serve as a potential alternative to the gold standard IP assay for detecting anti‐HMGCR autoantibodies. It can be considered a practical immunodiagnostic tool for diagnosing immune‐mediated necrotizing myopathy, particularly owing to its accessibility in routine laboratory settings.