Immunological Medicine最新文献

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.

Myasthenic crisis (MC) represents the most severe and life-threatening complication of myasthenia gravis (MG). Some patients exhibit refractory responses to conventional immunotherapies, including intravenous immunoglobulin and plasma exchange. This report describes a patient with MC refractory to repetitive high-dose steroids and intravenous immunoglobulin, requiring ventilator support. Within 2 days of eculizumab administration, significant improvement enabled ventilator discontinuation. Subsequent doses further ameliorated limb and pharyngeal weakness, leading to independence. A literature review that identified ten cases reported across five publications highlighted the favorable outcomes achieved with eculizumab in refractory MC, while concomitant respiratory infection was shown to complicate the recovery from MG-related respiratory failure. Although the randomized controlled trials have excluded MC cases, eculizumab has emerged as a promising option for rescue therapy in refractory MC. Larger studies that specifically include MC cases are warranted.

Immune checkpoint inhibitors (ICIs) can trigger immune-related adverse events (irAEs) and rheumatoid arthritis (RA) reactivation in cancer patients with pre-existing RA. Studies indicate RA reactivation occurs in approximately 50% of these patients, while new irAEs develop in 25-50% of ICI-treated patients. Furthermore, ICI-induced myocarditis has been reported to have a high mortality rate, ranging from 25% to 50%. No prior reports have detailed the clinical course of ICI-induced myocarditis in patients with RA. We describe a 77-year-old man with RA who developed myocarditis, myositis, and RA flare following treatment with the PD-LI inhibitor, atezolizumab, for small-cell lung cancer. High-dose glucocorticoid (GC) therapy and intravenous immunoglobulin improved myocarditis and myositis. Corticosteroid tapering led to organizing pneumonia, necessitating a dosage adjustment. Once resolved, tapering resumed. During irAEs treatment, the patient maintained a partial response without cancer recurrence for ten months, and required no further cancer-specific therapy. To our knowledge, this is the first detailed report of ICI-induced myocarditis in a patient with pre-existing RA. Our findings emphasize the importance of vigilant monitoring of both irAEs and RA disease activity for optimal patient management.

Postmenopausal osteoporosis (PO) is a prevalent condition that significantly impairs the quality of life in elderly women. While traditionally attributed to estrogen deficiency, emerging evidence suggests that immune dysregulation plays a critical role in its pathogenesis. This study investigates the osteoimmunological mechanisms underlying PO using an ovariectomy (Ovx) mouse model. Our findings indicate that Ovx mice exhibit substantial reductions in bone mineral density and bone volume, accompanied by a marked suppression of interleukin-4 (IL-4) and interferon-gamma (IFN-γ) production, particularly from natural killer T (NKT) cells. Lipidomic analysis of bone marrow further revealed an upregulation of omega-6 fatty acids, contributing to an inflammatory microenvironment that promotes excessive osteoclast activation. Notably, administration of the glycolipid OCH restored cytokine production and mitigated bone loss in Ovx mice, suggesting its therapeutic potential. These findings highlight the complex interplay between immune responses and lipid metabolism in PO and propose novel therapeutic strategies aimed at modulating immune function to prevent bone loss. This study offers valuable insights into the osteoimmunological mechanisms of PO and underscores the potential of immunomodulatory approaches for its management.

Gestational diabetes mellitus (GDM) is linked to an imbalance in gut microbiota composition, which can be transferred to the mother's offspring. Clostridium butyricum, known for its health benefits in diabetes and allergy, lacks sufficient data regarding its effect on the immune system's development in the offspring of mothers with GDM. This study assessed antibody responses against C. butyricum T2F3 in children of mothers at risk for GDM, involving 88 children aged 1-6 years. Antibody responses were measured with flow cytometry and immunoblot. Lower IgG median fluorescence intensity (MFI) values and fewer IgA and IgG bands against C. butyricum were detected in children of mothers with GDM. Maternal body mass index was positively associated with children's IgG MFI and number of IgG bands. Fewer IgA bands were detected in children with higher IgE levels, atopic dermatitis, asthma, and allergic rhinitis. More IgG bands were detected in children with higher anti-β-lactoglobulin IgG levels. Children with autoimmune risk-related HLA-DR3/DQ2.5 had fewer IgA bands, while those with neutral HLA-DR1/DQ5 had higher IgA, but lower IgG MFI. These results indicate that maternal prenatal changes could affect their offspring's immune response against C. butyricum. Moreover, C. butyricum could have a protective role against allergic sensitization.

Oral ulceration is the most common ulcerative condition in humans, yet its underlying etiology remains poorly understood. To identify potential causal genes involved in the pathogenesis of mouth ulcers, we applied summary data-based Mendelian randomization (SMR) using eQTL data from GTEx and CAGE, along with a transcriptome-wide association study (TWAS). The SMR analysis of GTEx data identified 41 significant probes, with LRRC37A4P, RP11-707O23.5, and RP11-259G18.3 standing out. In parallel, the CAGE SMR identified 67 probes corresponding to 58 genes, including CCR2, MGC57346, and C17orf69. TWAS further identified 181 significant genes, with 37 overlapping with GTEx SMR findings and 27 with CAGE SMR findings. Functional enrichment analysis revealed a strong involvement of immune-related pathways, especially those involving HLA-DRB1 and CCR2. Differential expression analysis reinforced the relevance of IL12RB1 and HLA-DRB1, which were consistently significant across both SMR and TWAS analyses. Collectively, these findings underscore the importance of immune-regulatory genes, particularly members of the CCR gene family and the HLA complex, in the genetic architecture of mouth ulcers. This integrative approach provides insights into potential therapeutic targets and advances our understanding of the genetic basis underlying this prevalent condition.

Immune checkpoint inhibitors (ICIs), such as anti-PD-1 antibody, have significantly changed the treatment landscape not only for unresectable melanoma but also for non-melanoma skin cancers. In addition, anti-PD-1 antibody administration methods have evolved and are now used in both the neoadjuvant and adjuvant settings. As these treatment strategies have been evaluated, it has become clear that understanding the role of the tumor microenvironment (TME) is critical to the success of anti-PD-1 antibody-based immunotherapy. For example, racial differences in the efficacy of immunotherapy in melanoma are influenced not only by tumor-related factors such as tumor mutational burden and microsatellite instability, but also by components of the TME, including tumor-associated macrophages, cancer-associated fibroblasts, and tumor-infiltrating lymphocytes (TILs), all of which can affect the therapeutic outcome of ICIs. Furthermore, studies conducted during the development of neoadjuvant therapies have shown that tumor-reactive TILs are densely localized within primary tumors and are closely associated with both treatment efficacy and the occurrence of immune-related adverse events. In this review, we discuss the therapeutic efficacy of currently available anti-PD-1 antibody-based immunotherapies for skin cancer and examine the role of the TME in influencing these therapeutic outcomes.

Despite the proven efficacy of belimumab and anifrolumab for SLE, their relative effectiveness remains uncertain owing to conflicting indirect comparison studies. We conducted a comparative effectiveness study using multicenter health records to evaluate the adjusted 12-month changes in the SLE Disease Activity Index 2000 (SLEDAI-2K), glucocorticoid dose, anti-DNA antibody titers, and CH50 levels, along with the adjusted hazard ratios of discontinuation and adverse events. A total of 58 bionaïve lupus patients (belimumab: 36, anifrolumab: 22) who initiated belimumab or anifrolumab on or after January 1, 2022 were identified and followed for up to 2 years. Adjusted changes in the SLEDAI-2K, glucocorticoid dose, and anti-DNA antibody titers were similar, with between-group differences (belimumab - anifrolumab) of -0.4 SLEDAI-2K units (95% CI: -4.8, 4.0), 1.4 mg/day (95% CI: -5.1, 7.9), and -2.7 IU/mL (95% CI: -27, 21), respectively. Belimumab was associated with a greater increase in adjusted CH50 levels (between-group difference: 5.3 CH50/mL, 95% CI: -8.9, 20) and a lower adjusted hazard ratio of discontinuation (0.68, 95% CI: 0.12, 3.7). Infection was the most common adverse event (belimumab: 31%, anifrolumab: 41%). Our findings suggest both treatments provide similar effectiveness, with belimumab offering potential benefits in CH50 levels, treatment continuity, and infection risk.

Immunoglobulin G replacement therapy prevents infections in patients with antibody deficiencies. Subcutaneous immunoglobulin (SCIg) has typically been administered via infusion pump, but the manual push technique offers a simple, convenient alternative method. The manual push technique is efficacious, well tolerated, quick to administer, offers increased dosing flexibility, and does not rely on a pump. Having various administration options available to patients provides greater treatment satisfaction and feelings of self-empowerment, which may improve compliance. Currently available literature published before 10 February 2022, that reported patient and healthcare professional experience with SCIg administered via manual push, were reviewed. Literature searches were performed using PubMed, Google and ClinicalTrials.gov using key words 'manual push', 'rapid push', 'immunoglobulin', 'subcutaneous immunoglobulin', 'SCIg', and 'primary immunodeficiency'. Real-world evidence demonstrates all delivery techniques provide similar efficacy, so treatment administration becomes about patient preference, hospital resources, cost-effectiveness/recovery and clinician attitude. To establish newer administration modalities such as manual push or prefilled syringes, there needs to be patient awareness of these options, then education and finally confidence in recommending these options. Adoption of newer administration modalities will help ensure patients receive the widest range of choice, thus improving compliance and their risk of recurrent and severe infection.