Current opinion in rheumatology最新文献

Purpose of review: Aberrant autoreactive innate and adaptive immune responses cause systemic autoimmune diseases. Autoimmunity has been linked to abnormal metabolic states, and immunometabolism has emerged as a critical field in understanding the pathogenesis of rheumatic diseases. We aimed to explore the latest research on metabolic reprogramming in various immune cell types, including T cells, B cells, neutrophils, dendritic cells, monocytes, and macrophages, in the context of rheumatic diseases.

Recent findings: Each immune cell utilizes preferred metabolic pathways, and the cell activation dramatically modifies metabolic status. The inhibition of these pathways alters cell survival, differentiation, proliferation, and cytokine production - all of which contribute to rheumatic disease progression.

Summary: Targeting metabolic pathways or introducing anti-inflammatory metabolites, such as itaconate, could be novel therapeutic strategies for rheumatic diseases. Further research should focus on strategies for translating basic research findings to bedside applications.

Purpose of review: This review provides an update on the rapidly growing field of engineered cellular therapies for autoimmune disorders, primarily focusing on clinical experience and correlative studies with chimeric antigen receptor (CAR) T-cells.

Recent findings: To date, two case series describing treatment with CAR T-cell therapy for systemic lupus erythematosus (SLE) suggest that drug-free remission can be sustained in patients with previously treatment-refractory disease. The outcomes of these studies are similar, despite the use of different CAR constructs and lymphodepletion regimens. Although it is not yet clear whether the patients described have truly been cured, the majority of remissions have remained durable up to last follow-up at 1-2 years from treatment. Meanwhile, mechanistic studies are providing a window into how transient B-cell depletion mediates lasting benefit. With the encouraging data in SLE, CAR T-cells and other novel B-cell-depleting agents (e.g. bispecific T-cell engagers) are now being evaluated as treatment for other autoimmune conditions, with the goal of durable response.

Summary: Recent reports highlight cellular therapies as a promising strategy for patients with treatment-refractory autoimmune conditions; however, there is still limited experience, and better insight into this therapeutic approach is expected to emerge rapidly.

Purpose of review: Systemic vasculitides are characterized by inflammation of blood vessels. Their classification is based on the size of the blood vessels involved - large, medium, or small. Vasculitis early diagnosis and reliable monitoring are crucial to establish a treatment plan and prevent serious complications. Based on these considerations and depending on the location of the affected vessels, the importance of imaging modalities including ultrasonography (US), magnetic resonance Imaging (MRI), magnetic resonance angiography (MRA), computed tomography (CT), computed tomography angiography (CTA), and [18F]-fluoro-2-deoxy- d -glucose positron emission tomography/computed tomography (FDG-PET/CT) has progressively increased. In addition to physical exam and laboratory data, these imaging tools offer complementary information about vascular changes occurring in vasculitis.This review summarizes the different imaging modalities being utilized to diagnose and monitor vasculitis.

Recent findings: The most recent update for the use of imaging in vasculitis is referenced in the 2023 European Alliance of Associations for Rheumatology (EULAR) recommendations and the American College of Rheumatology (ACR) guidelines in 2021. Recent advances in PET imaging in large vessel vasculitis include improved technological imaging acquisition and the use of novel radiotracers for cellular and immune targets. FDG-PET has now been demonstrated to have high sensitivity and specificity to detect temporal arteritis.

Summary: Imaging plays a significant role in the evaluation of vasculitis and continues to gain importance in the diagnosis and monitoring of disease activity. Differences exist between the ACR guidelines, which advocates for temporal artery biopsy, and the EULAR guidelines, which favors imaging modalities for the initial evaluation and diagnosis of large vessel vasculitis (LVV). Prerequisites for appropriate clinical management utilizing imaging in patients with vasculitis are the availability and access to skilled clinicians to interpret the images and the cost of these techniques not being prohibitive.

Purpose of review: To review recent advances in our understanding of the epidemiology, pathophysiology, and management of inclusion body myositis (IBM).

Recent findings: Recent epidemiologic studies have highlighted the morbidity and mortality associated with IBM, including the impact of dysphagia. Multiomic analyses of IBM tissues have identified new pathogenic pathways and biomarkers for use in clinical trials. New diagnostic criteria and outcome measures have been proposed to improve clinical trial design. Ongoing clinical trials are targeting T cells and autophagy.

Summary: Improvements in our understanding of IBM pathogenesis are identifying new pathways and biomarkers that need validation in larger cohorts. Exercise remains the primary therapeutic modality available, and new treatment targets are needed.

Purpose of review: Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by diffuse organ fibrosis and vasculopathy. Aberrant aging has been increasingly implicated in fibrotic diseases of the lung and other organs. The aim of this review is to summarize the established mechanisms of aging and how they may contribute to the pathogenesis of SSc.

Recent findings: Shortened telomeres are present in SSc patients with interstitial lung disease (SSc-ILD) and associate with disease severity and mortality. Although the cause of telomere length shortening is unknown, immune mechanisms may be at play. Senescent cells accumulate in affected organs of SSc patients and contribute to a pathologic cellular phenotype that can be profibrotic and inflammatory. In addition to identifying patients with a more severe phenotype, biomarkers of aging may help identify patients who have worse outcomes with immunosuppression.

Summary: Aging mechanisms, including telomere dysfunction and cellular senescence, likely contribute to the progressive fibrosis, vasculopathy, and immune dysfunction of SSc. Further work is needed to understand whether aberrant aging is an initiator or perpetuator of disease, and whether this is cell or organ specific. A better understanding of the role aging mechanisms play in SSc will contribute to our understanding of the underlying pathobiology and may also influence management of patients exhibiting the aging phenotype.

Purpose of review: In this review, we aimed to highlight recent findings from "-omics" studies in Behçet's disease.

Recent findings: Recent genomic studies in Behçet's disease identified possible risk loci associated with Behçet's disease related uveitis, neurologic involvement and gastrointestinal involvement. Additionally, sex-specific genetic effects were determined in Behçet's disease. Transcriptomic analyses of immune cells in Behçet's disease revealed that key inflammatory pathways such as NF-κB and MAPK have roles in Behçet's disease pathogenesis. Proteomic studies have highlighted the role of immune cell derived extracellular vesicles and identified potential biomarkers for vascular involvement and examined HLA I-bound immunopeptidomes. Metabolomics studies are still limited, but recent research has pointed to alterations in fatty acid metabolism and lipid profiles in Behçet's disease patient.

Summary: Omics studies have gained importance in the field of Behçet's disease through the generation of large data sets and efforts to extend their application are intensifying. These studies can provide opportunities for understanding Behçet's disease pathogenesis when they lead to testable hypotheses. Current challenges include the choice of appropriately homogeneous patient and control groups, effective data management and sharing, high cost and a rapidly increasing gap between the wealth of observational data generated and the relative paucity of controlled experimental efforts that could lead to mechanistic understanding.

Purpose of review: Urticarial vasculitis is a rare condition manifesting with a variety of clinical presentations ranging from skin limited lesions to life-threatening systemic illnesses. This review aims to highlight the recent findings on the etiology, diagnostic modalities, and therapeutic strategies and course of urticarial vasculitis.

Recent findings: In addition to well established triggers, urticarial vasculitis (UV) cases associated with severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) disease and COVID-19 vaccines, vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome, and adenosine deaminase (ADA) deficiency have been reported. A clinical-dermoscopic model for differentiating urticarial vasculitis has been developed with purpuric patches and globules favoring UV diagnosis and thus diminishing the need for histopathology. The efficacy of treatment modalities has been reviewed, and antihistamines, systemic corticosteroids, omalizumab, cyclophosphamide, tocilizumab, anti-interleukin (IL)-1 agents, and rituximab were shown to have the highest success rates. Regarding the durability of remission, rituximab, dapsone, and MMF were related to long-lasting treatment free responses. The course of hypocomplementemic urticarial vasculitis was investigated in an epidemiological study, revealing 5- and 10-year survival rates of 92% and 83%, respectively. Chronic obstructive pulmonary disease, septicemia, and end-stage renal disease were identified as causes of mortality.

Summary: With the aid of dermoscopy, a noninvasive tool, differentiation from chronic spontaneous urticaria can be made, and the need for histopathological examination can be diminished. Although clear definitions and consensus criteria for performing disease severity are lacking, careful screening is needed to tailor the treatment on an individual basis. Emerging infections like SARS-CoV 2, vaccines, and autoinflammatory disorders like VEXAS syndrome and ADA deficiency are new associations. The optimal use of well established agents like systemic corticosteroids and immunomodulators are mainstay treatment modalities, whereas IL-1 inhibitors, omalizumab, rituximab and Janus Kinase inhibitors may represent viable alternatives in selected cases.

Purpose of review: Pathologic abnormalities in skeletal muscle and the systemic vasculature are common in patients with systemic sclerosis (SSc). These abnormalities may lead to impaired systemic peripheral oxygen extraction (EO 2 ), known as neurovascular dysregulation, which may be because of abnormal blood flow distribution in the vasculature, microvascular shunting, and/or skeletal muscle mitochondrial dysfunction. Findings from invasive cardiopulmonary exercising testing (iCPET) provide important insights and enable diagnosis and treatment of this SSc disease manifestation.

Recent findings: Recent findings from noninvasive cardiopulmonary exercise testing (niCPET) support the existence of neurovascular dysregulation in patients with SSc. Invasive cardiopulmonary exercise testing (iCPET) has pointed to reduced systemic vascular distensibility as a possible mechanism for neurovascular dysregulation in patients with connective tissue diseases, including SSc.

Summary: Neurovascular dysregulation is likely an underappreciated cause of exercise impairment and dyspnea in patients with SSc in the presence or absence of underlying cardiopulmonary disease. It is posited to be related to microcirculatory and muscle dysfunction. Further studies are needed to clarify the pathophysiology of neurovascular dysregulation in SSc and to identify novel treatment targets and additional therapies.