Current opinion in rheumatology最新文献

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: This review summarizes the most recent approaches in managing cutaneous involvement, one of the main clinical manifestations of systemic sclerosis (SSc). The following article is written for clinicians and researchers looking for optimizing patient care and exploring new therapies.

Recent findings: Recent studies have shown advancements in the management of cutaneous manifestations of SSc. While mycophenolate remains the first-line treatment, other immunosuppressive therapies targeting different pathways have shown promising results. B-cell depleting agents, such as Rituximab (RTX), are being increasingly utilized for cutaneous scleroderma with positive outcomes. Intravenous immunoglobulins (IVIG) have also demonstrated potential benefit for refractory cases with advanced skin fibrosis.Moreover, emerging approaches such as autologous hematopoietic stem cell transplant (AHSCT) have been evaluated in clinical trials, with evidence suggesting its ability to reset the immune system and achieve remission in skin involvement in severe cases. Chimeric antigen receptor (CAR) T cell therapy is the most recent potential pathway to target refractory skin and systemic disease.

Summary: Management of cutaneous involvement in SSc remains challenging. The following study provides a comprehensive review of the most recent updates in treating cutaneous aspects (and associated complications) of SSc to help clinicians establish a more effective approach managing this condition.

Purpose of review: Antiphospholipid syndrome (APS) is an autoimmune, thromboinflammatory disease, which affects children and adults. There are particular features of the disease and nuances to diagnosis and management in a pediatric population, which must be appreciated to improve clinical care.

Recent findings: Pediatric-specific epidemiological studies highlight that pediatric APS is quite rare with incidence in some populations of 0.2 per 100 000. There are new classification criteria in APS, which include a wider range of clinical features increasingly identified in registry data and case series of pediatric APS, though validation in pediatric APS is still needed. There is a particularly high proportion of pediatric APS patients with noncriteria antiphospholipid antibodies (aPL). Recurrent thrombosis is especially common in pediatric APS, highlighting the difficulty of management of this disease with high morbidity in children.

Summary: Recent research has enhanced understanding of pediatric-specific APS epidemiology, laboratory findings, the wide variety of clinical features, and challenges in successful treatment. Future directions could include evaluation of potentially unique features in pediatric pathophysiology, an evaluation of the new APS classification criteria in children, broader prospective data on clinical and laboratory features, and a continued search for treatment beyond committing young patients to lifelong anticoagulation.

Purpose of review: This review provides an updated overview of the gut microbiota's involvement in spondyloarthritis (SpA) from a clinical perspective. It explores mechanisms by which the gut microbiota may influence SpA pathogenesis and considers the therapeutic implications of targeting the microbiome in SpA treatment.

Recent findings: The pathogenesis of SpA is multifactorial, involving genetic predisposition, external factors and dysregulation of the immune system. Recent studies have identified alterations in the gut microbiome of patients with SpA, including changes in microbial diversity and specific taxa linked to disease activity. HLA-B27 status seems to influence gut microbiota composition, potentially impacting disease progression. In HLA-B27 transgenic rats, the association between gut microbiota and SpA development has been confirmed, supporting findings from human studies. A compromised gut barrier, influenced by proteins like zonulin, may allow microbial antigens to translocate, triggering immune responses associated with SpA.

Summary: These findings highlight the potential for microbiota-modulating therapies, such as probiotics, prebiotics, diet and exercise, in managing SpA. However, methodological variability in human studies exposes the need for more rigorous research to better understand these associations. This may offer the opportunity to refine treatment strategies, offering a personalized approach to managing the disease.

Purpose of review: As the question of the pathogenesis of inflammatory myopathies remains unanswered, there has been a significant effort in recent years to investigate various components of the innate and adaptive immune systems, with evidence pointing that they work together to initiate and propagate the autoimmune response. This review aims to explore recent advancements in understanding the mechanisms underlying myopathies.

Recent findings: Recent research has concentrated on uncovering potential triggers, examining the role of immune cells, both lymphocytes and myeloids, and investigating the contribution of inflammatory mediators to the autoimmune response in inflammatory myopathies. Unsuccessful clinical trials helped reshape established hypotheses about pathogenesis, while genetic mutations offered clues to the disease's root causes. The pathogenic role of autoantibodies is being reconsidered based on transcriptional data. Repurposing existing medications to combat muscle fiber dysfunction is also emerging as a potential therapeutic approach.

Summary: Our understanding of inflammatory myopathies has evolved significantly as our understanding of the disease has grown. Even though breakthroughs have been documented on the underlying mechanisms of myopathies, important questions remain unanswered.

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.