Immunological Medicine最新文献

Lupus nephritis (LN) is one of the most important manifestations in patients with systemic lupus erythematosus (SLE). Although LN is associated with increased morbidity, mortality and healthcare costs, the advent of new immunosuppressive drugs and biologics in recent years has led to significant improvements in treatment outcomes. In addition to conventional dual therapy, evidence for triple therapy has been established. Triple therapy, which combines mycophenolate mofetil (MMF) with belimumab (BEL) or calcineurin inhibitors (CNIs, including voclosporin), or intravenous cyclophosphamide with BEL, has been recommended, particularly for active nephritis with poor prognostic factors. Since rapid reductions in proteinuria have been observed with CNIs, triple therapy combining MMF and CNIs have been conditionally recommended for LN patients with preserved renal function and severe proteinuria. In contrast, because BEL reduced disease activity and severe flares in non-renal symptoms, triple therapy including BEL has been conditionally recommended in LN patients with significant extra-renal SLE disease. Furthermore, the latest treatment recommendations from the European League Against Rheumatism had added the combination therapy of MMF plus obinutuzumab as an initial treatment option. In this review, we discuss the latest guidelines and recommendations for LN.

Azathioprine (AZA) is an established treatment for rheumatic diseases, but real-world safety data in Japanese patients remain limited. This study aimed to evaluate the real-world use and safety of AZA in Japan. A nationwide questionnaire survey was conducted, distributing forms to 1163 facilities, including university hospitals and Japan College of Rheumatology-certified institutions. Of these, 170 facilities (14.6%) responded. A total of 1943 patients with rheumatic diseases who initiated AZA between November 2000 and September 2023 were enrolled. Among them, 33.9% experienced adverse events (AEs), including hepatobiliary disorders (13.9%), gastrointestinal disorders (10.4%), blood and lymphatic system disorders (9.3%), infections (5.1%), and skin/subcutaneous disorders (2.4%). AZA therapy was discontinued in 468 (71.6%) of the 660 patients with AEs. The incidence of serious AEs (grade ≥3) was 2.7% and varied by rheumatic disease. Multivariate analysis identified older age (odds ratio [OR] 2.47, 95% confidence interval [CI]: 1.32-4.59) and systemic lupus erythematosus (OR 2.31, 95% CI: 1.09-4.87) as risk factors for serious AEs. This nationwide survey provides evidence of AZA-related AEs in Japanese patients with rheumatic diseases. AE incidence was relatively high, and serious AEs (grade ≥3) occurred more frequently in patients aged over 65 years and those with systemic lupus erythematosus.

The current study investigated acute circulatory dynamics changes induced by high-dose intravenous methylprednisolone pulse therapy (steroid pulse therapy). Eight patients who underwent steroid pulse therapy were included in the study. After steroid pulse therapy, plasma levels of brain and atrial natriuretic peptides were significantly increased compared with those before steroid pulse therapy (both p < 0.001). Echocardiography revealed that left ventricular end-diastolic diameter (LVDd) tended to increase after steroid pulse therapy (p = 0.055). Left atrial volume index (LAVI) also increased after steroid pulse therapy (p < 0.05). Peak early diastolic transmitral flow velocity (E wave) increased significantly (p < 0.05), and early diastolic mitral annular velocity tended to increase (p = 0.09). These findings indicate that steroid pulse therapy may increase cardiac preload, as suggested by the observed increases in LVDd, LAVI, and E wave velocity. Clinicians should remain mindful of this potential effect when administering steroid pulse therapy.

Inflammatory bowel disease (IBD) is a debilitating and treatment-refractory condition with a complex and incompletely understood etiology. Recent advances in neuroimmunology have revealed that intestinal homeostasis is regulated by bidirectional communication between the autonomic nervous system and the immune system. In particular, vagus nerve-mediated cholinergic anti-inflammatory signaling plays a central role in modulating intestinal immune responses and represents a key mechanism linking neural regulation to IBD pathogenesis and therapy. In parallel, the gut-brain axis has emerged as a critical regulator of intestinal inflammation and systemic disease. Psychological stress alters gut immune function through mechanisms involving enteric glial activation and microbiota-derived metabolites, contributing to treatment-resistant depression via immune activation and changes in short-chain fatty acid profiles. Moreover, gut microbiota dysbiosis has been implicated in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, potentially preceding central pathology through vagal signaling and systemic inflammation. Together, these findings position the gut microbiota as an immunological and neurological hub connecting intestinal, systemic, and brain health. This review summarizes recent advances in gut-brain axis-mediated immune regulation in IBD and highlights emerging bioelectronic neuromodulation strategies targeting autonomic circuits as promising non-pharmacological approaches to restore gut immune balance.

This study was conducted to reveal specific clinical features, outcomes and risk factors of organ damage in patients with systemic lupus erythematosus (SLE) with neuropsychiatric (NP) symptoms upon initial onset. Patients with newly diagnosed SLE at our institute between 2010 and 2022 were enrolled. Patients who exhibited NP symptoms at initial onset constituted the initial onset NPSLE (Ini-NPSLE) group, and their clinical features were compared with those of patients without NP symptoms (SLE NP- group). Among 90 patients with newly onset SLE (mean age 37.7 years), there were 20 patients in the Ini-NPSLE group and 70 patients in the SLE NP- group. General clinical characteristics were similar between the two groups, except for diagnostic delay, arthritis and avascular necrosis. The Ini-NPSLE group showed significantly higher SLE Disease Activity Index scores at admission (24.8 vs. 15.6) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) scores (1.55 vs. 0.53) at the end of follow-up. Logistic regression analysis revealed that patients' age and NPSLE were associated with organ damage (SDI ≥ 1) in patients with newly onset SLE. This study suggests that clinicians must focus on early NP symptoms to manage later organ damage in patients with SLE.

BHLHE40 is a transcription factor regulating proinflammatory cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) in CD4⁺ T cells. Although implicated in autoimmune inflammation, its regulation by interleukin (IL)-1 signaling in human CD4⁺ T cells remains unclear. Peripheral blood (PB) from healthy controls (HCs) and patients with giant cell arteritis (GCA) was analyzed using flow cytometry to assess BHLHE40 expression across helper T cells. Immunohistochemistry was performed on the aortas of IL-1 receptor antagonist knockout (IL-1Rn KO) mice and temporal artery biopsies from GCA patients. We also analyzed public microarray datasets and CD4⁺ T cells stimulated with anti-CD3/CD28 and IL-1β. We identified BHLHE40 expression in T cells in the IL-1Rn KO mice and GCA-inflamed arteries. BHLHE40 expression was higher in helper T subsets than in naïve CD4⁺ T cells. Co-stimulation with IL-1β and anti-CD3/CD28 induced stronger BHLHE40 expression than CD3/CD28 alone. Microarray data showed increased expression of BHLHE40 in CD4⁺ T cells from the PB of GCA patients. IL-1 signaling enhances BHLHE40 expression during CD4⁺ T cell activation. Its sustained expression in inflamed tissues suggests a disease-relevant pathway linking IL-1 signaling to pathogenic T cell responses in GCA.

The cGAS-STING signaling pathway plays a critical role in the immune defense against DNA viruses and in autoimmunity, coordinating a cascade of events that enhance cytokine production, particularly type I interferons. This review summarizes recent advancements in understanding the pathway's impact on various ocular diseases, including age-related macular degeneration (AMD), diabetic retinopathy, and uveitis. Activation of this pathway by cytoplasmic DNA from either damaged retinal cells or external pathogens induces inflammatory responses that may accelerate disease progression. Moreover, the paper explores new therapeutic approaches that target this pathway, offering insights into how modulation of cGAS-STING signaling could reduce inflammation and improve clinical outcomes. The emerging research in this area suggests potential for innovative treatments in ocular inflammation and degenerative conditions.

Autoimmune diseases such as systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome have a significant impact on pregnancy, potentially exacerbating SLE symptoms and leading to miscarriage, pre-eclampsia and other pregnancy complications. To ensure the safety of SLE patients during pregnancy, experts have conducted in-depth research and provided recommendations. Therefore, it is necessary to provide a thorough summary of the current status, hotspots and emerging trends in this research field. We systematically searched the Web of Science Core Collection database for studies on SLE during pregnancy from 1 January 2003 to 24 March 2024. We then utilized CiteSpace to generate a knowledge visualization map. This analysis included a total of 2239 studies on SLE during pregnancy. The yearly volume of publications exhibits a persistent increasing trend. The United States had the highest number of publications and was the leading country, while the Czech Republic had the highest centrality and influence. The research focused on three main areas: (1) pregnancy outcomes in autoimmune diseases, (2) newborn-related diseases and complications and (3) medication management for patients with SLE during pregnancy. Our study offers both a visual and scientific synopsis of research concerning SLE during pregnancy, furnishing valuable insights and opening up new avenues for researchers.

The skeletal system is responsible for the body's support and motor functions, and can be pathologically affected by factors, such as metabolism, autoimmune inflammation, tumors, and infections. Regarding tissue localization and biological function, the immune system is deeply involved in the physiological and pathological processes of the skeletal system. As a regulator and effector cell of the innate immune system, natural killer (NK) cells can exert cytotoxic effects through cell contact and immunomodulatory effects through cytokine secretion. In the past 30 years, many advances have been made regarding the role of NK cells and their derived cytokines on bone and joints. In this review, the role of NK cells in the physiological activities of bone remodeling is summarized first, focusing on osteoclast differentiation and function. Subsequently, the roles of NK cells in osteoarthritis, bone tumors, and bone diseases caused by microbial infections are described, meanwhile, some conflicting research results are discussed. By reviewing the state-of-the-art progress of NK cells in the above-mentioned bone physiological and pathological processes, it is helpful to clarify the blind spots of current research and provide some references for the integrated evaluation of immune factors in the study of skeletal system diseases.