Immunological Medicine最新文献

Sarcoidosis is a multi-systemic granulomatous disease of unknown etiology. Its association with lymphoproliferative disorders is termed sarcoidosis-lymphoma syndrome, which is typically characterized by sarcoidosis preceding lymphoma. However, the development of sarcoidosis after lymphoma remission is rare. A 72-year-old woman with a history of diffuse large B-cell lymphoma, treated 11 years earlier, was admitted with a rash and weakness in the lower limbs. Multiple inflammatory lesions, predominantly in the lower limbs, were detected using computed tomography and fluorodeoxyglucose positron emission tomography, and a diagnosis of systemic sarcoidosis was established via biopsies of the skin lesion. We reviewed 11 cases of sarcoidosis with cutaneous manifestations after lymphoma treatment, including the present case. In addition, we emphasized the importance of considering cutaneous sarcoidosis in the differential diagnosis of post-treatment skin lesions alongside lymphoma recurrence, as well as the need for histopathological confirmation.

A 68-year-old Japanese woman was diagnosed with palmoplantar pustulosis. She presented with anterior chest pain and swelling, as well as pain in the right first finger. Initially, antibiotics was ineffective, the patient was diagnosed with non-bacterial osteomyelitis. Computed tomography of the chest revealed a sternal bone thickening pattern, and technetium-99m bone scintigraphy showed accumulations in the left sternoclavicular joint and sternal angle. Additionally, contrast-enhanced magnetic resonance imaging revealed osteitis in the sternal scapes and body. Based on these findings, the patient was diagnosed with pustulotic arthro-osteitis. The swelling of the right first finger repeatedly worsened and resolved spontaneously, the first right distal phalanx was amputated to rule out infection and malignancy. Histopathological evaluation revealed evidence of chronic non-bacterial osteitis, and associated with pustulotic arthro-osteitis. We report this case as histopathological examination is rarely performed to confirm the diagnosis of finger osteitis associated with pustulotic arthro-osteitis.

Long COVID has emerged as a significant global health issue, affecting individuals across a wide spectrum of initial disease severity. While its definition and prevalence vary across studies, persistent symptoms such as fatigue, cognitive dysfunction, respiratory difficulties, and cardiovascular complications have been widely reported. Multiple pathophysiological mechanisms have been proposed, including incomplete viral clearance, reactivation of latent viruses, immune dysregulation, autoimmunity, endothelial dysfunction, microbiome alterations, and mitochondrial impairment. These interconnected processes are thought to contribute to chronic inflammation and multi-organ disease. To date, there are no established therapies for Long COVID, and management primarily focuses on symptomatic relief and rehabilitation. Vaccination has been shown to reduce the incidence of Long COVID, and emerging strategies, including antiviral agents, immune-modulating therapies, microbiome restoration, and mitochondria-targeted interventions, are under investigation. This review summarizes the current understanding of the epidemiology, pathophysiology, organ-specific manifestations, and potential therapeutic approaches for Long COVID, aiming to provide insights into future research directions and clinical management strategies.

Still's disease is a systemic inflammatory disorder involving both innate and adaptive immunity. Although its pathogenesis remains incompletely understood, immune cells such as neutrophils, macrophages, and T cells, along with pro-inflammatory cytokines, particularly interleukin (IL)-1, IL-6, IL-18, and interferon-γ (IFN-γ), play central roles in disease development. While glucocorticoids remain the first-line treatment, the advent of molecular-targeted therapies has revolutionized management. IL-1 and IL-6 inhibitors have shown efficacy in controlling disease activity and reducing glucocorticoid dependence. However, treatment responses vary among patients due to immunological heterogeneity. Recent studies have proposed clustering patients based on clinical features, immune cell profiles, and dominant cytokine signatures to help predict therapeutic responses. In addition, novel therapies targeting IL-18, IFN-γ, and Janus kinase (JAK) signaling pathways are emerging as promising options for refractory cases. This review summarizes current insights into the immunopathogenesis of Still's disease and explores the evidence supporting molecular-targeted therapies, paving the way toward personalized treatment strategies.

Anti-cyclic citrullinated peptide (CCP) antibodies typically present before rheumatoid arthritis (RA) but appear (seroconvert) after disease onset in some patients. This study analyzed factors related to anti-CCP seroconversion. Fifty-six consecutive patients with anti-CCP negative RA were enrolled. The first determination of anti-CCP status was defined as the baseline. Anti-CCP was then reassessed with an interval of 77 (±41) months. Demographics and baseline characteristics were compared between patients with and without anti-CCP seroconversion. Moreover, relevant studies were systematically reviewed. Six of the 56 patients experienced anti-CCP seroconversion (<4.5-12.4 [8.5-65.7] U/mL). These patients were more likely to have interstitial lung disease and HLA-DRB1 shared epitope (SE) alleles and to use biological disease-modifying antirheumatic drugs (bDMARDs). From the systematic review and meta-analysis, bDMARDs, bone erosions, HLA-DRB1 SE and rheumatoid factor positivity were identified as factors related to anti-CCP seroconversion. By selectively screening for anti-citrullinated protein antibody responses, an expansion of the repertoire was observed after the onset of RA. The seroconversion of anti-CCP after the onset of RA is associated with the typical features of RA and may therefore represent an overlooked seropositive disease.

In adult systemic sclerosis (SSc), salt-and-pepper skin changes can be used to diagnose diffuse cutaneous SSc during the early stages. However, reports of juvenile SSc (JSSc) with salt-and-pepper skin changes are unavailable. A 12-year-old Japanese girl presented with JSSc, showing scleroderma, Raynaud's phenomenon, digital ulcers, and telangiectasia. She developed scleroderma at 10 years of age and later experienced salt-and-pepper skin changes. Laboratory findings revealed positive antinuclear and anti-U3-RNP antibodies. After being diagnosed with JSSc based on established criteria, she received two courses of intravenous methylprednisolone (IVMP) followed by mycophenolate mofetil (MMF). Her modified Rodnan skin score improved from 25 to 0, and the salt-and-pepper changes resolved. This case represents the first report of the presence and subsequent improvement of salt-and-pepper skin changes in JSSc treated with MMF following IVMP. Recognition of salt-and-pepper changes may serve as an early clinical clue, prompting further diagnostic evaluation for JSSc and supporting early diagnosis of adult SSc. Moreover, MMF after IVMP may exert beneficial anti-fibrotic effects, potentially improving pigment changes by controlling scleroderma.

Immune checkpoint inhibitor (ICI)-mediated release of immune suppression involves the risk of (re)activating the immune responses to self-tissues, which are considered 'side effects' of this therapy, immune-related adverse events (irAEs). Although the incidence of certain types of irAEs appears to be considerably increased in older patients, the effect of chronological aging on irAE development and their causative immunological mechanism are unclear. This review summarizes the potential relevance of chronological and cellular aging, such as age-associated changes in T-cell functions and aged environmental factors, and inflamm-aging, in shaping irAE-inducing immune responses. Several immunological perspectives on aging may provide insights into the practical consideration of the toxicity risks of ICIs, particularly in elderly patients. These insights from patient specimens and pre-clinical animal models will help establishing mechanism-based management strategies, including stratification of irAE-prone patients, and broadening the patient population that benefits from cancer immunotherapy, even in a younger population.

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder whose pathophysiology remained poorly understood until recently. For decades, treatment relied primarily on topical corticosteroids, with no therapies specifically targeting its underlying mechanisms. However, the introduction of dupilumab in 2017 - the first biologic for AD - marked a turning point, catalyzing rapid advances in both therapeutic strategies and pathophysiological insights. As of 2025, four biologics and three oral Janus kinase inhibitors have been approved for clinical use. Additionally, novel topical therapies with distinct mechanisms of action have emerged. Although certain challenges still remain with the use of these novel treatments, AD is increasingly becoming a condition that can be effectively controlled in a wide range of patients.

Cervical cancer, a prevalent malignancy caused by high-risk HPV strains, remains a significant challenge due to its ability to evade the immune system, particularly T cell-mediated responses. This study aims to explore the research landscape surrounding T cell-mediated immune evasion in cervical cancer through a comprehensive bibliometric analysis. Using data from the Web of Science Core Collection (2014-2023), we employed VOSviewer, CiteSpace, and the R package "bibliometrics" to conduct co-citation and co-occurrence analyses, identifying key trends, contributors, and research hotspots. Our analysis included 930 studies from 68 countries, with China, the USA, and the Netherlands as the leading contributors. Emerging topics include immune checkpoint inhibitors, PD-L1, and tumor microenvironment modulation, highlighting the growing focus on immune-based therapies. This study provides valuable insights into the role of T cells in cervical cancer progression and offers a foundation for future research directions aimed at improving immunotherapy outcomes in cervical cancer patients.

Leukopenia can occur because of lymphopenia, neutropenia or both. Leukopenia appearing as a common hematological manifestation of systemic lupus erythematosus (SLE) is typically mild, but potentially life-threatening. However, no consensus has been reached on treatment strategies for severe leukopenia in SLE. An 18-year-old man was diagnosed with SLE based on fever, malar and discoid rash, leukopenia, hypocomplementemia, and a positive result for anti-nuclear antibodies. Despite administration of high-dose glucocorticoids combined with immunosuppressants (including intravenous cyclophosphamide, mycophenolate mofetil, tacrolimus, and azathioprine) and intravenous immunoglobulin G (IgG) treatment, leukocyte count declined to 50/μL, accompanied by positive anti-neutrophil IgG antibodies. Bone marrow biopsy revealed normocellular marrow without hemophagocytosis. The patient developed febrile dyspnea due to pulmonary infection. Administration of rituximab (375 mg/m² weekly for 4 weeks) led to rapid, sustained recovery of leukocyte count. The patient then recovered from respiratory failure with anti-microbial therapy. Prednisolone was successfully tapered to 5 mg/day. This case suggests that rituximab may provide an effective therapeutic option for severe treatment-refractory leukopenia in SLE.