Current opinion in rheumatology最新文献

Purpose of review: Antinuclear autoantibodies represent a serological hallmark of systemic sclerosis (SSc), with anticentromere, antitopoisomerase-I, and anti-RNA polymerase III antibodies routinely assessed for diagnosis, clinical subset classification, and prognosis. In addition, an increasing number of autoantibodies have been demonstrated to play a pathogenic role by mediating different SSc manifestations. This review aims to give an overview on autoantibodies as putative biomarkers in SSc and discuss their possible pathogenic role as triggers of cell dysfunctions.

Recent findings: Over the years, different autoantibodies have been proposed as biomarkers aiding in diagnosis, disease subtype classification, disease progression prediction, organ involvement, as well as in understanding treatment response. Increasing literature also indicates functional autoantibodies as direct contributors to SSc pathogenesis by exerting agonistic or antagonistic activities on their specific cognate targets.

Summary: In SSc, search and validation of novel autoantibodies with higher diagnostic specificity and more accurate predictive values are increasingly needed for early diagnosis and specific follow-up, and to define the best therapeutic option according to different disease subsets. Moreover, since autoantibodies are also emerging as functional pathogenic players, a better unraveling of their possible pathomechanisms becomes essential to identify new targets and develop promising therapeutic agents able to neutralize their effects.

Purpose of review: Antimelanoma differentiation antigen 5-dermatomyositis (MDA5-DM) is a complex and serious systemic autoimmune disease that primarily affects the skin and lungs. In this review, we aimed to provide new insights into the clinical features, pathogenesis, and practical management approach for this disease.

Recent findings: Although lung lesions are prominent in most patients with MDA5-DM, they are now recognized as heterogeneous diseases. Peripheral blood lymphocyte count can serve as a simple and reliable laboratory parameter for categorizing MDA5-DM into three subgroups: mild, medium, and severe. Recent studies have implicated viral infection, genetic factors, autoimmunity against MDA5, multiple immune cells, and interferons as significant contributors to MDA5-DM pathogenesis. In addition to traditional treatments with glucocorticoids and immunosuppressants, many new approaches, including new biologics and targeted agents, have been explored. Additionally, infection is a common complication of MDA5-DM, and prophylaxis or treatment of the infection is as important as treating the primary disease.

Summary: Knowledge of clinical characteristics and pathogenesis of MDA5-DM has grown in recent years. Although many new therapeutic approaches have been explored, further studies are required to confirm their efficacy.

Purpose of review: This review evaluates recent advancements in disease-modifying therapies for axial spondyloarthritis (axSpA).

Recent findings: A recent study could not demonstrate an additional effect of NSAID therapy on golimumab [Tumor Necrosis Factor-α inhibitor (TNFi)] on structural progression; however, this might be due to the fact that the study was underpowered. While DMARDs have shown promise in suppressing inflammation, their impact on structural progression remains uncertain. A well powered trial showed no difference in spinal progression between secukinumab [Interleukin17A inhibitor (IL17Ai)] and adalimumab-biosimilar (TNFi). Preliminary data on Janus kinase inhibitors (JAKi) focus on MRI findings but lack evidence on radiographic spinal progression. While some studies suggest promising outcomes, others reveal limitations and inconclusive findings.

Summary: Recent studies explore the effectiveness of NSAIDs, biological disease-modifying antirheumatic drugs like TNFi and IL-17i, as well as JAK inhibitors in axSpA. Conflicting evidence surrounds these therapies' ability to impede structural progression, with challenges in study design and interpretation. Moreover, changes in demographics and treatment methods underscore the importance of examining trends over time when assessing disease outcomes. Ultimately, ongoing research could benefit from new imaging tools when evaluating therapeutic strategies for modifying disease progression in axSpA.

Purpose of review: This review summarizes the recent evidence regarding the epidemiology of inflammatory bowel disease (IBD) associated sacroiliitis, including the prevalence, pathogenesis, role of imaging, and therapeutic challenges.

Recent findings: Sacroiliitis is an underappreciated musculoskeletal manifestation of IBD, a chronic inflammatory condition of the gut affecting the younger population. Untreated sacroiliitis can lead to joint destruction and chronic pain, further adding to morbidity in IBD patients. Recent publications suggest sacroiliitis can be detected on abdominal imaging obtained in IBD patients to study bowel disease, but only a small fraction of these patients were seen by rheumatologists. Early detection of IBD-associated sacroiliitis could be achieved by utilization of clinical screening tools in IBD clinics, careful examination of existing computed tomography and MRI studies, and timely referral to rheumatologist for further evaluation and treatment. Current treatment approaches for IBD and sacroiliitis include several targeted biologic therapies, but IBD-associated sacroiliitis has limited options, as these therapies may not overlap in both conditions.

Summary: With the advances in imaging, sacroiliitis is an increasingly recognized comorbidity in IBD patients. Future studies focusing on this unique patient population will expand our understanding of complex pathophysiology of IBD-associated sacroiliitis and lead to identification of novel targeted therapies for this condition.

Purpose of review: Pain is the most common and often most troublesome feature of chronic autoimmune diseases such as psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA). A predominant concept is that the main source of pain is from disease-induced tissue inflammation and structural damage, activating peripheral nerve fibers which relay to the central nervous system. This mechanism is nociceptive pain and the presumption has been that controlling inflammation will be sufficient to reduce this form of pain. However, despite control of inflammation, patients may still have significant residual pain.

Recent findings: We are learning that there are additional pain mechanisms, neuropathic and nociplastic, that are often operative in patients with rheumatologic conditions, that can significantly influence pain experience, quantitation of disease activity, and may benefit from therapeutic approaches distinct from immunotherapy. Neuropathic pain arises from diseased or damaged nerve tissue and nociplastic pain reflects sensitization of the central nervous system due to multiple genetic, neurobiologic, neural network dysregulation, and psychosocial factors. Pain arising from these mechanisms influence assessment of disease activity and thus needs to be factored into decision-making about immunotherapy efficacy.

Summary: This review addresses the importance of accurately assessing the complex mechanisms of pain experience in patients with PsA and AxSpA to more appropriately manage immunomodulatory, neuromodulatory, and nonpharmacologic therapies.

Purpose of review: To evaluate the current applications and prospects of artificial intelligence and machine learning in diagnosing and managing axial spondyloarthritis (axSpA), focusing on their role in medical imaging, predictive modelling, and patient monitoring.

Recent findings: Artificial intelligence, particularly deep learning, is showing promise in diagnosing axSpA assisting with X-ray, computed tomography (CT) and MRI analyses, with some models matching or outperforming radiologists in detecting sacroiliitis and markers. Moreover, it is increasingly being used in predictive modelling of disease progression and personalized treatment, and could aid risk assessment, treatment response and clinical subtype identification. Variable study designs, sample sizes and the predominance of retrospective, single-centre studies still limit the generalizability of results.

Summary: Artificial intelligence technologies have significant potential to advance the diagnosis and treatment of axSpA, providing more accurate, efficient and personalized healthcare solutions. However, their integration into clinical practice requires rigorous validation, ethical and legal considerations, and comprehensive training for healthcare professionals. Future advances in artificial intelligence could complement clinical expertise and improve patient care through improved diagnostic accuracy and tailored therapeutic strategies, but the challenge remains to ensure that these technologies are validated in prospective multicentre trials and ethically integrated into patient care.

Purpose of review: RA is characterized by the presence of autoantibodies among which rheumatoid factors (RFs) and antimodified protein antibodies (AMPA) are serological hallmarks of the disease. In recent years, several novel insights into the biology, immunogenetics and clinical relevance of these autoantibodies have been obtained, which deserve to be discussed in more detail.

Recent findings: RFs from RA patients seem to target distinct epitopes which appear to be quite specific for RA. Determination of immunoglobulin A (IgA) isotypes of RF and anticitrullinated protein antibodies (ACPA) may provide prognostic information because their presence is associated with reduced therapeutic responses to TNF inhibitors. Furthermore, IgA levels are increased in RA patients and IgA immune complexes are more potent than immunoglobulin G (IgG) complexes in inducing NET formation. Concerning AMPAs, investigations on variable domain glycosylation (VDG) revealed effects on antigen binding and activation of autoreactive B cells. Studies on pathogenetic involvement of ACPA suggest Janus-faced roles: on the one hand, ACPA may be involved in joint destruction and pain perception while on the other hand protective anti-inflammatory effects may be attributed to a subset of ACPAs.

Summary: The autoimmune response in RA is extremely complex and still far from being fully understood. Antibodies are not only valuable diagnostic biomarkers but also seem to play pivotal roles in the pathophysiology of RA.

Purpose of review: This review aims to provide an overview of the genes and molecular pathways involved in monogenic lupus, the implications for genome diagnosis, and the potential therapies targeting these molecular mechanisms.

Recent findings: To date, more than 30 genes have been identified as contributors to monogenic lupus. These genes are primarily related to complement deficiency, activation of the type I interferon (IFN) pathway, disruption of B-cell and T-cell tolerance and metabolic pathways, which reveal the multifaceted nature of systemic lupus erythematosus (SLE) pathogenesis.

Summary: In-depth study of the causes of monogenic lupus can provide valuable insights into of pathogenic mechanisms of SLE, facilitate the identification of effective biomarkers, and aid in developing therapeutic strategies.

Purpose of review: This review will discuss selected emerging molecular targets and associated potential therapeutic agents for rheumatoid arthritis (RA)-directed treatment.

Recent findings: Agents in active development for RA treatment include those targeted to CD40 and CD40 ligand, programmed death protein 1 (PD-1), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Several other molecules with a strong theoretical role in RA pathogenesis and/or demonstrated efficacy in other autoimmune diseases are also being evaluated as potential drug targets in preclinical or translational studies in RA. These targets include interleukin 1 receptor associated kinases 1 and 4 (IRAK1, IRAK4), tyrosine kinase 2 (Tyk2), bradykinin receptor 1 (B1R), OX40 and OX40 ligand.

Summary: Identification of molecular targets for RA treatment remains an active area of investigation, with multiple therapeutic agents in clinical and preclinical development.