Autoimmunity reviews最新文献

Spondyloarthritis (SpA) is a term to describe a group of chronic inflammatory rheumatic diseases, which have common pathophysiological, genetic, and clinical features. Under the umbrella term SpA, two main groups are subsumed: axial SpA (radiographic axSpA and non-radiographic axSpA) and peripheral SpA (with the leading representative being psoriatic arthritis (PsA) but also arthritis associated with inflammatory bowel disease (IBD), reactive arthritis, and undifferentiated pSpA). The key clinical symptom in axSpA is chronic back pain, typically with inflammatory characteristics, which starts in early adulthood, while the leading clinical manifestations of peripheral SpA (pSpA) are arthritis, enthesitis, and/or dactylitis. Furthermore, extra-musculoskeletal manifestations (EMMs) (acute anterior uveitis, psoriasis, and IBD) can accompany axial or peripheral symptoms. All these factors need to be taken into account when making treatment decisions in SpA patients. Despite the major advances in the treatment landscape over the past two decades with the introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) and most recently targeted synthetic DMARDs (tsDMARDs), a relevant proportion of patients still does not achieve the desired state of remission (=absence of disease activity). With this implementation of new treatment modalities, clinicians now have more choices to make in the treatment algorithms. However, despite generalized treatment recommendations, all factors need to be carefully considered when deciding on the optimal treatment strategy for an individual patient in clinical practice, aiming at an important first step towards personalized treatment strategies in SpA. In this narrative review, we focus on the efficacy of approved and emerging treatment options in axSpA and PsA as the main representative of pSpA and discuss their selective effect on the different manifestations associated with SpA to provide guidance on drivers of treatment decisions in specific situations.

Background

This study aims to describe the global burden trends of six immune-mediated inflammatory diseases (IMIDs), including asthma, atopic dermatitis (AD), inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis and rheumatoid arthritis (RA), from 1990 to 2021, and analyze patterns of cross-country inequalities.

Methods

The estimates for the number of disability-adjusted life-years (DALYs) and age-standardized DALYs rates (ASDR), along with the 95 % uncertainty intervals (UI) for asthma, AD, IBD, MS, psoriasis and RA, were obtained from the Global Burden of Diseases Study 2021. The estimated annual percentage change (EAPC) was used to quantify the global burden trends of these six IMIDs from 1990 to 2021. Additionally, slope index of inequality and concentration index were employed to quantify the distributional inequalities in the burden of IMIDs.

Results

From 1990 to 2021, the global ASDR of psoriasis (EAPC = 0.23 %, 95 % UI: 0.21 to 0.25) and RA (EAPC = 0.05 %, 95 % UI: 0.01to 0.10) showed an increasing trend, while the global ASDRs of asthma (EAPC = −1.91 %, 95 % UI: −1.98 to −1.84), AD (EAPC = −0.26 %, 95 % UI: −0.27 to −0.26), IBD (EAPC = −0.52 %, 95 % UI: −0.60 to −0.43) and MS (EAPC = −0.39 %, 95 % UI: −0.45 to −0.33) demonstrated declining trends. The cross-country inequality analysis reveals pronounced heterogeneity in the burden of these six IMIDs.

Conclusions

The global distribution of the DALYs burden attributable to IMIDs exhibits significant disparities across regions, underscoring an urgent need for innovative and comprehensive management strategies to address this heterogeneous landscape.

Objective

Methods

Results

Conclusion

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by widespread inflammation affecting various organs. This review discusses the role of oxidative stress and gut microbiota in the pathogenesis of SLE and evaluates the therapeutic potential of intravenous immunoglobulins (IVIg). Oxidative stress contributes to SLE by causing impairment in the function of mitochondria, resulting in reactive oxygen species production, which triggers autoantigenicity and proinflammatory cytokines. Gut microbiota also plays a significant role in SLE. Dysbiosis has been associated to disease's onset and progression. Moreover, dysbiosis exacerbates SLE symptoms and influences systemic immunity, leading to a breakdown in bacterial tolerance and an increase in inflammatory responses.

High-dose IVIg has emerged as a promising treatment for refractory cases of SLE. The beneficial effects of IVIg are partly due to its antioxidant property, reducing oxidative stress markers and modulating the immune responses. Additionally, IVIg can normalize the gut flora, as demonstrated in a case of severe intestinal pseudo-obstruction.

In summary, both oxidative stress and dysregulation of microbiota are pivotal in the pathogenesis of SLE. The use of IVIg may improve the disease's outcome. Future research should be directed to elucidating the precise mechanisms by which oxidative stress and microbiota are linked with autoimmunity in SLE in developing targeted therapies.

The International Consensus on ANA Patterns (ICAP) is an ongoing international initiative dedicated to harmonizing technical and interpretation aspects of the HEp-2 IFA test. Comprised of internationally recognized experts in autoimmunity and HEp-2 IFA testing, ICAP has operated for the last 10 years by promoting accurate reading, interpretation, and reporting of HEp-2 IFA images by professionals involved in various areas related to autoimmune diseases, such as clinical diagnostic laboratories, academic research, IVD industry, and patient care. ICAP operates through continuous information exchange with the international community and encourages the participation of younger experts from all over the world. The 7th ICAP workshop has addressed several aspects that originated from this interaction with the international community and has effectively established objective goals and tasks to be delivered over the next two years. Some of these are outlined in this article, including the planning of three audio-visual educational modules to be posted at the www.anapattern.org website, the classification of two novel HEp-2 IFA patterns, the implementation of a project dedicated to continuously updating the information on the clinical and immunologic relevance of the HEp-2 IFA patterns, and the launch of two additional branches of the HEp-2 Clinical and Immunological (HEp-2 CIC) project.

Autoimmune diseases constitute a broad, heterogenous group with many diverse and often overlapping symptoms. Even so, they are traditionally classified as either systemic, rheumatic diseases or organ-directed diseases.

Several theories exist about autoimmune diseases, including defective self-recognition, altered self, molecular mimicry, bystander activation and epitope spreading. While there is no consensus about these theories, it is generally accepted that genetic, pre-disposing factors in combination with environmental factors can result in autoimmune disease. The relative contribution of genetic and environmental factors varies between diseases, as does the significance of individual contributing factors within related diseases.

Among the genetic factors, molecules involved in antigen (Ag) recognition, processing, and presentation stand out (e.g., MHC I and II) together with molecules involved in immune signaling and regulation of cellular interactions (i.e., immuno-phenotypes). Also, various immuno-deficiencies have been linked to development of autoimmune diseases. Among the environmental factors, infections (e.g., viruses) have attracted most attention, but factors modulating the immune system have also been the subject of much research (e.g., sunlight and vitamin D).

Multiple sclerosis currently stands out due to a very strong and proven association with Epstein-Barr virus infection, notably in cases of late infection and in cases of EBV-associated mononucleosis.

Thus, a common picture is emerging that both systemic and organ-directed autoimmune diseases may appropriately be described as auto-immuno-deficiency syndromes (AIdeSs), a concept that emphasizes and integrates existing knowledge on the role of immuno-deficiencies and chronic infections with development of overlapping disease syndromes with variable frequencies of autoantibodies and/or autoreactive T cells.

This review integrates and exemplifies current knowledge on the interplay of genetically determined immuno-phenotypes and chronic infections in the development of AIdeSs.

Autoimmune diseases comprise a spectrum of disorders characterized by the dysregulation of immune tolerance, resulting in tissue or organ damage and inflammation. Their prevalence has been on the rise, significantly impacting patients' quality of life and escalating healthcare costs. Consequently, the prediction of autoimmune diseases has recently garnered substantial interest among researchers. Despite their wide heterogeneity, many autoimmune diseases exhibit a consistent pattern of paraclinical findings that hold predictive value. From serum biomarkers to various machine learning approaches, the array of available methods has been continuously expanding. The emergence of artificial intelligence (AI) presents an exciting new range of possibilities, with notable advancements already underway. The ultimate objective should revolve around disease prevention across all levels. This review provides a comprehensive summary of the most recent data pertaining to the prediction of diverse autoimmune diseases and encompasses both traditional biomarkers and the latest innovations in AI.

The present review reports the history of our scientific collaboration with Professor Shoenfeld's group. The collaboration started at the end of the 80s and was mainly focused on studies on the pathogenetic mechanisms of the anti-phospholipid syndrome (APS). Following the initial collaborative studies on antibodies against endothelium in systemic autoimmune vasculitis, we were able to use a similar strategy in APS. This line of research has resulted in the characterization of beta 2 glycoprotein I (β2GPI)-dependent anti-phospholipid antibodies (aPL) as mechanisms capable of mediating an endothelial perturbation crucial for the pathogenesis of APS. Thanks to these studies, the collaboration has led to the characterization of the membrane receptors for β2GPI and the cellular signaling resulting from antibody binding. This mechanism has also been shown to mediate the aPL effect on other cell types involved in APS pathogenesis. Finally, the exchange of information made it possible to replicate and extend the setting of animal models of the syndrome, which proved to be valuable tools for understanding the pathogenesis of the syndrome. It has been a long story recently refueled by common studies on the similarity of pro-inflammatory and pro-coagulant endotheliopathy in APS and in COVID-19.