Autoimmunity reviews最新文献

Systemic autoimmune diseases are complex conditions characterized by an immune system dysregulation and an aberrant activation against self-antigens, leading to tissue and organ damage. Even though genetic predisposition plays a role, it cannot fully explain the onset of these diseases, highlighting the significant impact of non-heritable influences such as environment, hormones and infections. The exposome represents all those factors, ranging from chemical pollutants and dietary components to psychological stressors and infectious agents.

Epigenetics, which studies changes in gene expression without altering the DNA sequence, is a crucial link between exposome and the development of autoimmune diseases. Key epigenetic mechanisms include DNA methylation, histone modifications, and non-coding RNAs.

These epigenetic modifications could provide a potential piece of the puzzle in understanding systemic autoimmune diseases and their connection with the exposome.

In this work we have collected the most important and recent evidence in epigenetic changes linked to systemic autoimmune diseases (systemic lupus erythematosus, idiopathic inflammatory myopathies, ANCA-associated vasculitis, and rheumatoid arthritis), emphasizing the roles these changes may play in disease pathogenesis, their potential as diagnostic biomarkers and their prospective in the development of targeted therapies.

Objective

To quantify the magnitude of the risk of total and type-specific cardiovascular and cerebrovascular diseases (CCVD) in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV).

Method

Searches of PubMed, Embase, and the Cochrane Library were conducted. Observational studies were included if they reported data on CCVD in AAV patients. Pooled risk ratios (RR) with 95% confidence intervals were calculated.

Result

Fourteen studies met the inclusion criteria, comprising 20,096 AAV patients (over 46,495 person-years) with 5757 CCVD events. Compared with non-vasculitis population, AAV patients showed an 83% increased risk of incident CCVD (1.83 [1.37–2.45]; n = 10), 48% for coronary artery disease (1.48 [1.26–1.75]; n = 9), and 56% for cerebrovascular accident (1.56 [1.22–1.99]; n = 9). For type-specific CCVD, the risks of myocardial infarction, stroke, heart failure were increased by 67% (1.67 [1.29–2.15]; n = 6), 97% (1.97 [1.19–3.25]; n = 8) and 72% (1.72 [1.28–2.32]; n = 4), whereas there was only a trend toward a higher risk of angina pectoris (1.46 [0.90–2.39]; n = 2), and ischemic stroke (1.88 [0.86–4.12]; n = 4). Subgroup analyses by AAV type found significantly increased CCVD risk in both granulomatosis with polyangiitis (1.87 [1.29–2.73]; n = 7) and microscopic polyangiitis (2.93 [1.58–5.43]; n = 3). In three studies reporting impact of follow-up period after AAV diagnosis, the CCVD risk was significantly higher in the first two years after diagnosis than the subsequent follow-up (2.23 [2.00–2.48] vs. 1.48 [1.40–1.56]; p < 0.01). Significant heterogeneity existed in the main analyses.

Conclusion

This meta-analysis demonstrates that AAV is associated with increased risks of overall and type-specific CCVD, especially within two years after AAV diagnosis.

Giant cell arteritis (GCA), the most common primary vasculitis in adults, is a granulomatous systemic vasculitis usually affecting the aorta and its major branches, particularly the carotid and vertebral arteries. Although remission can be achieved in most patients with GCA using high-dose glucocorticoids (GC), relapses are frequent, occurring in >40% of GC-only treated patients, mostly during the first two years after diagnosis. Relapsing courses lead to high GC exposure, increasing the risk of treatment-related adverse effects. Although tocilizumab is an efficacious GC-sparing therapy that allows increased sustained remission and reduced cumulative GC doses, relapses are common after drug discontinuation.

This narrative review examines the most relevant features of relapses in GCA, including its definition, classification, frequency, clinical, laboratory, and imaging characteristics, chronology, probable pathophysiology, and predictive factors. In addition, we discuss treatment options for relapsing patients and the effect of relapses on patient outcomes.

Background

The early detection and management of (progressive) interstitial lung disease in patients with connective tissue diseases requires the attention and skills of a multidisciplinary team. However, there are currently no well-established standards to guide the daily practice of physicians treating this heterogenous group of diseases.

Research question

This paper aimed to identify gaps in scientific knowledge along the journey of patients with connective tissue disease-related interstitial lung disease and to provide tools for earlier identification of interstitial lung disease and progressive disease.

Study Design and Methods

The opinions of an international expert panel, which consisted of pulmonologists and rheumatologists were collected and interpreted in the light of peer-reviewed data.

Results

Interstitial lung disease is a common complication of connective tissue diseases, but prevalence estimates vary by subtype. Screening and monitoring by means of clinical examination, chest radiography, pulmonary function testing, and disease-specific biomarkers provide insight into the disease activity of patients presenting with connective tissue diseases in a routine setting. Multiple phenotypic and genotypic characteristics have been identified as predictors of the development and progression of interstitial lung disease. However, these risk factors differ between subtypes. To ensure earlier diagnosis of rapidly progressive phenotypes, a risk-based method is necessary for determining the need for HRCT and additional testing.

Interpretation

To reduce the underdiagnosis of CTD-ILDs in clinical practice, a standardized and systematic multidisciplinary risk-based approach is suggested. Collaboration across disciplines is essential for the management of CTD-ILD.

Background and aims

The escalating prevalence of IBD within specific age cohorts, 10–24 and 50–69 years, necessitates a refined understanding of its epidemiological patterns. Prior investigations have often been constrained by their limited scope, particularly in employing age-specific analyses and utilizing advanced statistical methods such as joinpoint regression. Our research examines these demographic segments to elucidate the epidemiological trajectory of IBD.

Methods

This study analyzed GBD 2019 data on IBD, focusing on age groups 10–24 and 50–69. We integrated the socio-demographic index for socio-economic context and employed joinpoint regression to analyze time-segmented disease trends, prioritizing average annual percent change for a comprehensive view.

Results

A notable global decline in IBD incidence, particularly in the 50–69 age group, was observed. The 10–24 cohort, however, presented a marginal rise across three decades, with a discernible decline between 2010 and 2019. The study also revealed pivotal gender disparities, with increasing incidence rates in males, especially in the High-income Asia Pacific region. Conversely, females demonstrated decreasing trends across the board. Regional variations accentuated East Asia's escalated IBD incidence and prevalence, whereas high-income North American and Asia-Pacific regions, along with Europe, reflected the highest age-standardized incidence rates.

Conclusion

The burden of IBD between 1990 and 2019 presents notable disparities across different regions and age demographics. While older populations are seeing a decrease in IBD incidence, young adults and adolescents in regions like East Asia and high-income Asia Pacific are experiencing a concerning uptick. This uneven distribution, influenced by both age and gender, underscores the multifaceted nature of IBD's global impact.

The surrounding non-cancer cells and tumor cells that make up the tumor microenvironment (TME) have various metabolic rhythms. TME metabolic heterogeneity is influenced by the intricate network of metabolic control within and between cells. DNA, protein, transport, and microbial levels are important regulators of TME metabolic homeostasis. The effectiveness of immunotherapy is also closely correlated with alterations in TME metabolism. The response of a tumor patient to immunotherapy is influenced by a variety of variables, including intracellular metabolic reprogramming, metabolic interaction between cells, ecological changes within and between tumors, and general dietary preferences. Although immunotherapy and targeted therapy have made great strides, their use in the accurate identification and treatment of tumors still has several limitations. The function of TME metabolic heterogeneity in tumor immunotherapy is summarized in this article. It focuses on how metabolic heterogeneity develops and is regulated as a tumor progresses, the precise molecular mechanisms and potential clinical significance of imbalances in intracellular metabolic homeostasis and intercellular metabolic coupling and interaction, as well as the benefits and drawbacks of targeted metabolism used in conjunction with immunotherapy. This offers insightful knowledge and important implications for individualized tumor patient diagnosis and treatment plans in the future.

Mitochondria are the main sites of aerobic respiration in the cell and mainly provide energy for the organism, and play key roles in adenosine triphosphate (ATP) synthesis, metabolic regulation, and cell differentiation and death. Mitochondrial dysfunction has been identified as a contributing factor to a variety of diseases. The kidney is rich in mitochondria to meet energy needs, and stable mitochondrial structure and function are essential for normal kidney function. Recently, many studies have shown a link between mitochondrial dysfunction and kidney disease, maintaining mitochondrial homeostasis has become an important target for kidney therapy. In this review, we integrate the role of mitochondrial dysfunction in different kidney diseases, and specifically elaborate the mechanism of mitochondrial reactive oxygen species (mtROS), autophagy and ferroptosis involved in the occurrence and development of kidney diseases, providing insights for improved treatment of kidney diseases.

Background

Obesity is the risk factor for psoriasis. Therefore, we conducted a comprehensive review and meta-analysis to determine the prevalence of obesity in patients with psoriasis.

Methods

We examined four databases from their inception to October 2023 and used the Agency for Healthcare Research and Quality and the Newcastle-Ottawa Scale to assess the quality of observational studies. Data analysis was conducted by R language. Meta-regression, sensitivity and subgroup analyses were used to evaluate inter-study heterogeneity. Egger's test and funnel plots were used to evaluate publication bias.

Results

The global prevalence of psoriasis and obesity comorbidity was 25% (95% confidence interval [CI]: 0.21–0.30). Furthermore, the co-morbidity rate was 18% (95% CI: 0.11–0.24) in children and adolescents, and 35% (95% CI: 0.30–0.39) in adults. The gender-specific prevalence rates were 23% (95% CI: 0.16–0.32) in men and 38% (95% CI: 0.20–0.61) in women. Africa had the highest prevalence (60%, 95% CI: 0.21–0.99), followed by Asia (40%, 95% CI: 0.28–0.51), while Europe and North America had similar prevalence rates at 34% (95% CI: 0.27–0.41) and 31% (95% CI: 0.27–0.38), respectively. Regarding psoriasis severity, obesity prevalence was higher in moderate psoriasis (36%, 95% CI: 0.20–0.64) and lower in mild psoriasis (27%, 95% CI: 0.16–0.46). The prevalence of obesity in the patients with severe psoriasis was 30% (95% CI: 0.20–0.45).

Conclusion

This study underscores the importance of identifying and treating obesity in patients with psoriasis to mitigate disease progression. However, more high-quality observational studies are required to elucidate their global prevalence and comorbid associations.

Efferocytosis is a crucial process whereby phagocytes engulf and eliminate apoptotic cells (ACs). This intricate process can be categorized into four steps: (1) ACs release “find me” signals to attract phagocytes, (2) phagocytosis is directed by “eat me” signals emitted by ACs, (3) phagocytes engulf and internalize ACs, and (4) degradation of ACs occurs. Maintaining immune homeostasis heavily relies on the efficient clearance of ACs, which eliminates self-antigens and facilitates the generation of anti-inflammatory and immunosuppressive signals that maintain immune tolerance. However, any disruptions occurring at any of the efferocytosis steps during apoptosis can lead to a diminished efficacy in removing apoptotic cells. Factors contributing to this inefficiency encompass dysregulation in the release and recognition of “find me” or “eat me” signals, defects in phagocyte surface receptors, bridging molecules, and other signaling pathways. The inadequate clearance of ACs can result in their rupture and subsequent release of self-antigens, thereby promoting immune responses and precipitating the onset of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. A comprehensive understanding of the efferocytosis process and its implications can provide valuable insights for developing novel therapeutic strategies that target this process to prevent or treat autoimmune diseases.

T cells are key drivers of the pathogenesis of autoimmune diseases by producing cytokines, stimulating the generation of autoantibodies, and mediating tissue and cell damage. Distinct mitochondrial metabolic pathways govern the direction of T-cell differentiation and function and rely on specific nutrients and metabolic enzymes. Metabolic substrate uptake and mitochondrial metabolism form the foundational elements for T-cell activation, proliferation, differentiation, and effector function, contributing to the dynamic interplay between immunological signals and mitochondrial metabolism in coordinating adaptive immunity. Perturbations in substrate availability and enzyme activity may impair T-cell immunosuppressive function, fostering autoreactive responses and disrupting immune homeostasis, ultimately contributing to autoimmune disease pathogenesis. A growing body of studies has explored how metabolic processes regulate the function of diverse T-cell subsets in autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), autoimmune hepatitis (AIH), inflammatory bowel disease (IBD), and psoriasis. This review describes the coordination of T-cell biology by mitochondrial metabolism, including the electron transport chain (ETC), oxidative phosphorylation, amino acid metabolism, fatty acid metabolism, and one‑carbon metabolism. This study elucidated the intricate crosstalk between mitochondrial metabolic programs, signal transduction pathways, and transcription factors. This review summarizes potential therapeutic targets for T-cell mitochondrial metabolism and signaling in autoimmune diseases, providing insights for future studies.