Immunologic Research最新文献

Entheses are specialized tissues that connect ligaments and tendons to the bone surface and are frequently involved in seronegative spondyloarthritis. Enthesitis can also be detected in patients with metabolic disorders (MD), regardless of baseline autoimmune rheumatic disease, posing real diagnostic challenges. The present review discusses the pathophysiology of enthesitis and metabolic-associated enthesitis, the clinical relevance of metabolic disorders on enthesitis-related outcomes, diagnostic challenges for adequate differential diagnosis, and possible therapeutic strategies to improve clinical outcomes. PubMed/MEDLINE and the Cochrane Library were searched for original articles, systematic reviews, and meta-analyses. References were screened according to a hierarchical analysis of studies by title, abstract, and full text, collected, presented, and discussed. Metabolic-associated enthesitis is attributable to mechanical stress/overload due to weight excess typically observed in metabolic disorders (MD), such as overweight/obese comorbid patients, metabolic syndrome (MS), and type 2 diabetes (T2D). Interleukin 1β, 6, 17, 18, and 23 and tumor necrosis factor-α play a crucial role in initiating and maintaining entheseal inflammation. Chronic hyperglycemia and insulin resistance lead to a vicious circle as they stimulate, upon activated, specialized T cells to produce these specific cytokines, thus maintaining entheseal inflammation chronically. MD is associated with more severe clinical presentation, worse response to pharmacological treatments, and poor entheseal outcomes also in patients with existing seronegative spondyloarthritis. Non-immune-mediated metabolic-associated enthesitis poses a real diagnostic challenge, possibly underestimating cases and potential misdiagnoses. From a therapeutic viewpoint, glucose control improvement and weight loss are associated with relevant amelioration of entheseal-related outcomes. Pharmacological and non-pharmacological interventions aiming to reduce body weight, improve glucose control and insulin sensitivity, and attenuate inflammation are desirable to achieve the therapeutic target. Glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter type 2 inhibitors, in add-on to non-steroidal anti-inflammatory drugs and immunomodulators when necessary, may have a therapeutic rationale in patients with metabolic-associated enthesitis. Awareness of metabolic-associated enthesitis is essential to improve the accuracy of differential diagnosis in patients with MD and prescribe appropriate therapeutic strategies. However, basic and clinical research is needed to understand the role of "antihyperglycemic" agents in better managing metabolic-associated enthesitis.

Referring to a broad spectrum of the autonomic symptoms, autonomic disorders, and general dysfunction of the autonomic nervous system, dysautonomia is one of the common and under-recognized comorbidities of a wide variety of systemic disease, including diabetes, autoimmune disorders, vitamin deficiencies, and hormonal dysregulation. The most common autonomic disorders encountered in clinical practice are postural orthostatic tachycardia syndrome (POTS), neurocardiogenic syncope (NCS), and orthostatic hypotension (OH), which may be undiagnosed or often mislabeled with psychiatric disorders. Typical clinical features of dysautonomia, such as orthostatic dizziness/lightheadedness, orthostatic intolerance, palpitations, exercise intolerance, cognitive dysfunction, and fatigue, should prompt a diagnostic investigation for dysautonomia, which includes an in-office 10-min stand test or a tilt table test in conjunction with other autonomic function tests if available. Treatment approach consists of non-pharmacologic and pharmacologic therapies with beta blockers, midodrine, ivabradine, pyridostigmine, fludrocortisone, stimulants, and other medications. In clinical setting, dysautonomia may present a diagnostic and therapeutic challenge in patients with various systemic disorders and may require a high index of suspicion on the part of the clinician. Importantly, diagnosing and treating dysautonomia is critical to providing comprehensive and personalized medical care to complex patients with chronic illness, who are typically highly symptomatic with multi-systemic complaints as a result of comorbid, and often undiagnosed, dysautonomia.

22q11.2 deletion syndrome (22qDS) is a heterogeneous genetic disorder associated with a variety of clinical manifestations, including congenital heart disease, neuropsychiatric disorders, hypocalcemia, and immunological deficiencies. This study aimed to characterize the clinical and immunological features of patients with 22qDS in a cohort from Colombia. We conducted a retrospective study over a 3-year period, including 40 patients with confirmed 22qDS. Demographic, clinical, and immunological data were collected from medical records. The cohort had a median age of 3 years, with a balanced sex distribution. Heart defects were present in 75% of patients, followed by ear and craniofacial abnormalities (50%) and language disorders (45%). Immunological work-up revealed low T cell subsets in 42% of patients, with a decrease in T cell lymphopenia observed with age. Humoral deficiencies were also common, with 20% of patients exhibiting selective IgM deficiency and 17% presenting with hypogammaglobulinemia. Recurrent infections were observed in 48% of patients, particularly pneumonia and otitis. Vaccine responses to protein-based antigens and polysaccharides were frequently impaired. The findings highlight the clinical and immunological heterogeneity of 22qDS in this Latin American cohort. Multidisciplinary care, early diagnosis, and immunological management are essential for improving outcomes in these patients.

Immune dysfunction in patients with systemic lupus erythematosus (SLE) increases susceptibility to infections, complicating their management. Identifying risk factors for infections is essential for improving clinical outcomes. A meta-analysis was conducted to evaluate factors associated with infection risk in patients with SLE. Relevant studies were retrieved from PubMed, Web of Science, Embase, and Scopus databases from inception to November 2023. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis was performed using R software (version 4.3.1). Factors analyzed included age, gender, active disease stage, diabetes mellitus, kidney injury, hydroxychloroquine, high-dose glucocorticoids, immunosuppressive drugs, lymphopenia, anti-dsDNA, and complement 3 (C3). Twenty-one studies were included. The analysis identified several factors significantly associated with increased infection risk: age (OR = 1.02, 95% CI 1.01-1.04), being male (OR = 1.66, 95% CI 1.19-2.33), active disease stage (OR = 1.74, 95% CI 1.25-2.43), diabetes mellitus (OR = 1.64, 95% CI 0.92-2.93), kidney injury (OR = 1.78, 95% CI 1.37-2.30), high-dose glucocorticoids (OR = 2.40, 95% CI 1.88-3.80), immunosuppressive drugs (OR = 2.24, 95% CI 1.15-4.38), lymphopenia (OR = 3.59, 95% CI 2.42-5.33), and low C3 (OR = 2.38, 95% CI 1.13-5.03). Older age, male gender, active disease, diabetes, kidney injury, high-dose glucocorticoid use, immunosuppressants, lymphopenia, and decreased C3 levels may increase the risk of infections in SLE. These findings highlight the importance of individualized infection prevention strategies in high-risk patients.

Quantum dots, because of some of their fascinating features, like continuous radiation emission, crossing the biological barrier, and potential for drug carrying, have emerged as versatile nanomaterials in enormous applications relating to drug development and health sciences. Among such quantum dots, carbon quantum dots have gained widespread attention due to their low toxicity, high biocompatibility, and excellent photostability. The present work investigates the immunomodulatory properties of CQDs with diverse chemical characteristics against primary macrophages and whole splenocytes. Since macrophages are important regulators of immune responses, their isolation and activation by toll-like receptor agonists were performed to evaluate the production of pro-inflammatory cytokines and intracellular signaling pathways. Our data indicate that different CQD formulations possess specific immunomodulatory activities, while some of them reveal adjuvant capabilities; others act anti-inflammatory. Importantly, the zinc-containing CQDs enhance pro-inflammatory responses, which may find applications as vaccine adjuvants. These findings highlight the therapeutic possibilities of CQDs in the treatment of inflammatory diseases and enhancement of vaccine efficacy.

This study aimed to evaluate the global burden of inflammatory bowel disease (IBD) among women of reproductive age (15-49 years) from 1990 to 2021, analyze its association with socio-demographic index (SDI), and identify age-period-cohort (APC) effects to inform region-specific public health strategies. Using data from the Global Burden of Disease (GBD) 2021 study, we assessed age-standardized incidence (ASIR), prevalence (ASPR), mortality (ASMR), and disability-adjusted life years (ASDR) across 204 countries. Statistical analyses included Pearson correlation to evaluate SDI associations, decomposition analysis to quantify burden drivers, and APC modeling to disentangle age, period, and cohort effects. In 2021, the global ASIR, ASPR, ASMR, and ASDR for IBD in women of reproductive age were 4.38, 45.90, 0.50, and 17.75 per 100,000, respectively. The health burden of IBD in women of reproductive age varies by region. Australasia has the highest ASIR and ASPR globally, while these metrics are lowest in Central Latin America. Western Europe exhibits the highest ASMR, whereas Oceania has the lowest. In terms of ASDR North America, with its higher income, bears the heaviest burden, while Oceania experiences the lightest. Furthermore, APC analysis revealed age-specific risks peaking at 45-49 years, and significant cohort effects in middle/low-SDI regions, where post-1977 birth cohorts showed elevated incidence. Period effects highlighted diverging trends: stable incidence in high-SDI regions vs. rising rates in mid-SDI regions due to urbanization and lifestyle shifts. The IBD burden among reproductive-aged women is rising disproportionately, shaped by SDI gradients and demographic transitions. High-SDI regions require strategies targeting aging populations and comorbidities, while low/middle-SDI regions need investments in early diagnosis and equitable care.

Endoplasmic reticulum (ER) stress induced by hepatitis B virus (HBV) infection is associated with the development of liver fibrosis. Golgi protein 73 (GP73) is increased during HBV infection. Nevertheless, whether GP73 during HBV infection mediates ER stress in liver fibrosis is still poorly understood. TGF-β1 was used to induce HepG2.2.15 cells to establish liver fibrosis cells model. GP73 expression was evaluated using qRT-PCR analysis and Western blot. HepG2.2.15 cells viability and proliferation were assessed via CCK-8 assay and EdU assay, respectively. The protein levels of α-SMA, fibronectin, collagen I and collagen III for liver fibrosis, GRP78, p-PERK, p-eIF2α, ATF4 and CHOP for ER stress, as well as p-Smad2 and Smad2 were evaluated by Western blot. TGF-β1 incubation obviously elevated GP73 expression, while GP73 knockdown reduced the GP73 levels in HBV-transfected HepG2215 cells. GP73 knockdown reversed the effects of TGF-β1 exposure on HepG2.2.15 cells viability and proliferation. The protein levels of liver fibrosis marker, ERS marker and p-Smad2 were remarkably increased following TGF-β1 stimulation, which were counteracted by GP73 silence or the application of 4-phenylbutyric acid (4-PBA). However, these results were opposite after tunicamycin (TM) treatment. In conclusion, knockdown of GP73 potentially impeded the advancement of liver fibrosis via mediating ERs through Smad2 signal pathway.

Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis (TB), modulates host immune responses by regulating various cytokines. Precise regulation of these cytokines renders the host pathogen-free, whereas their dysregulation increases the susceptibility to infection. Hence, induction of host protective cytokines using immunomodulators to promote M. tuberculosis clearance has a rewarding impact in the context of TB treatment. This study explored the immunomodulatory activity of 4-(Benzyloxy)phenol (4-BOP) in mycobacteria infected differentiated THP-1 cells through IL-35 (an anti-inflammatory cytokine) production. Initially, we observed an increased mRNA and protein level expression of IL-35 and its cognate receptor upon 4-BOP treatment in mycobacteria-infected dTHP-1 cells. IL-35 receptor activation further led to phosphorylation of JAK1/STAT3, culminating in increased phagosome-lysosome fusion through elevation of intracellular Ca²⁺ level. Blocking IL-35 receptors using siRNA-mediated approach against IL-12Rβ2 and gp130 or the JAK1/STAT3 associated signaling with specific inhibitors like Baricitinib and Stattic promoted the intracellular mycobacterial survival by compromising Ca²⁺-phagosome-lysosome fusion pathway. Further, we identified a direct regulatory role of p53 (known to be activated by 4-BOP) on IL-35 production, and inhibition of p53 using PFT-α surprisingly abrogated the IL-35 mediated signaling axis. Collectively, our results demonstrated a host defensive role of 4-BOP-induced Il-35 signaling in mycobacteria-infected dTHP-1 cells through the JAK1/STAT3 mediated Ca²⁺-phagosome-lysosome fusion pathway. These results suggest that 4-BOP may serve as a potent HDT candidate for regulating inflammation and enhancing host defense in TB infection.

Acute myeloid leukaemia is an aggressive hematologic malignancy that remains exceedingly difficult to treat despite recent advancements. High expression of CD47 on leukemic blasts interacts with the inhibitory receptor SIRP-alpha (SIRP-α) on innate immune cells, resulting in a strong "don't eat me" signal. Therefore, identifying AML patients who could benefit from immune-targeted therapies is crucial SIRP-β2 is predominantly expressed in myeloid cells and positively regulates innate anticancer immunity. Furthermore, endogenously expressed SIRP-β2 potentiates cancer cell trogocytosis by granulocytes. Here, we delineate the role of SIRP-β2 in AML. High expression of SIRP-β2 is independently associated with favorable overall survival (OS) and event free survival (EFS) independent of the ELN intermediate risk group. SIRP-β2 is more prevalent in the more committed FAB M4 and M5 subgroups. SIRP-β2 is also expressed on normal myeloid cells in patient samples, with higher expression on tumor-suppressive M1 macrophages than on adverse prognostic and tumor-supportive M2 macrophages. In line with this, co-culture of macrophages/neutrophils with ectopically expressed SIRP-β2 tumor cells results in an increased phagocytosis/trogocytosis treated with anti-CD47. These data indicate that AML patients with high SIRP-β2 AML expression could significantly benefit from innate immune-targeting therapies such as CD47 immune checkpoint inhibitor.

Statins were introduced as lipid-lowering agents that inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase; they are commonly administered to reduce cholesterol levels for cardioprotective purposes. Further studies suggested that statins have cholesterol-reducing-independent properties and exert pleiotropic therapeutic properties, including antioxidant, anti-inflammatory, anti-fibrotic, neuroprotective, and other beneficial effects. Adhesion molecules, including selectins, integrins, cadherins, CD44, and the immunoglobulin superfamily (IgSF) members, are essential mediators for those biological functions. The current review discusses studies performed in in vitro and in vivo in physiological and pathological models focusing on adhesion molecules such as Lymphocyte function-associated antigen-1 (LFA-1), macrophage-1 antigen (Mac-1), P-selectin, E-selectin, very late activation antigens-4 (VLA-4), and nectins that are therapeutically targeted by different types of statins and that highlight the potential therapeutic utility of statins for diseases other than cardiovascular disease.