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Indian Journal of Dermatology,... 2023The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is a key regulatory signaling system for cellular proliferation, differentiation,... (Review)
Review
The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is a key regulatory signaling system for cellular proliferation, differentiation, and apoptosis. In addition, JAK signaling pathway plays critical roles in orchestrating immune response through its interactions with the cytokine receptors and the transcriptions factors. Several key cytokines use JAK-STAT signaling proteins to transduce intra-cellular signals which are involved in the pathogenesis of autoimmune and inflammatory diseases such as in psoriatic disease (psoriasis, psoriatic arthritis), atopic dermatitis, alopecia areata, vitiligo, rheumatoid arthritis, ankylosing spondylitis, lupus erythematosus, Sjogren's syndrome, and other autoimmune diseases. In recent years, understandings of the molecular mechanisms of JAK-STAT pathway in the inflammatory proliferative cascades of autoimmune diseases has led to the development of JAK inhibitors and has opened a new dimension for the treatment of systemic and cutaneous inflammatory diseases. In this symposium we have provided a broad perspective on the use of Janus kinase inhibitors in cutaneous autoimmune diseases.
Topics: Humans; Janus Kinase Inhibitors; Janus Kinases; STAT Transcription Factors; Signal Transduction; Skin Diseases; Autoimmune Diseases
PubMed: 37609754
DOI: 10.25259/IJDVL_8_2023 -
Intensive Care Medicine Jan 2024Autoimmune diseases encompass a broad spectrum of disorders characterized by disturbed immunoregulation leading to the development of specific autoantibodies, resulting... (Review)
Review
Autoimmune diseases encompass a broad spectrum of disorders characterized by disturbed immunoregulation leading to the development of specific autoantibodies, resulting in inflammation and multiple organ involvement. A distinction should be made between connective tissue diseases (mainly systemic lupus erythematosus, systemic scleroderma, inflammatory muscle diseases, and rheumatoid arthritis) and vasculitides (mainly small-vessel vasculitis such as antineutrophil cytoplasmic antibody-associated vasculitis and immune-complex mediated vasculitis). Admission of patients with autoimmune diseases to the intensive care unit (ICU) is often triggered by disease flare-ups, infections, and organ failure and is associated with high mortality rates. Management of these patients is complex, including prompt disease identification, immunosuppressive treatment initiation, and life-sustaining therapies, and requires multi-disciplinary involvement. Data about autoimmune diseases in the ICU are limited and there is a need for multicenter, international collaboration to improve patients' diagnosis, management, and outcomes. The objective of this narrative review is to summarize the epidemiology, clinical features, and selected management of severe systemic autoimmune diseases.
Topics: Humans; Autoimmune Diseases; Lupus Erythematosus, Systemic; Intensive Care Units; Vasculitis; Autoantibodies
PubMed: 38112769
DOI: 10.1007/s00134-023-07266-7 -
Nature Reviews. Rheumatology Mar 2024Sjögren syndrome is a phenotypically varied autoimmune disorder that can occur alone in primary Sjögren syndrome or in association with other connective tissue... (Review)
Review
Sjögren syndrome is a phenotypically varied autoimmune disorder that can occur alone in primary Sjögren syndrome or in association with other connective tissue diseases (CTDs), including rheumatoid arthritis, systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). The estimation of the prevalence and incidence of Sjögren syndrome varies depending on diagnostic criteria and study design, making it difficult to estimate geographical and temporal trends. Nonetheless, disease phenotype is influenced by geographical origin, which is a risk factor for systemic activity. Whether mortality in primary Sjögren syndrome is increased compared with that of the general population is not yet known, but extra-glandular manifestations, in particular lymphomas, are clear risk factors for mortality. In CTDs associated with Sjögren syndrome, lymphoma risk seems higher than that of patients with CTD alone, and there is potentially lower disease activity in SLE with Sjögren syndrome and in SSc with Sjögren syndrome than in SLE or SSc alone.
Topics: Humans; Sjogren's Syndrome; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Arthritis, Rheumatoid; Autoimmune Diseases; Scleroderma, Systemic
PubMed: 38110617
DOI: 10.1038/s41584-023-01057-6 -
RMD Open Nov 2023Autoimmune disorders occur when immune cells go wrong and attack the body's own tissues. Currently, autoimmune disorders are largely treated by broad immunosuppressive... (Review)
Review
Autoimmune disorders occur when immune cells go wrong and attack the body's own tissues. Currently, autoimmune disorders are largely treated by broad immunosuppressive agents and blocking antibodies, which can manage the diseases but often are not curative. Thus, there is an urgent need for advanced therapies for patients suffering from severe and refractory autoimmune diseases, and researchers have considered cell therapy as potentially curative approach for several decades. In the wake of its success in cancer therapy, adoptive transfer of engineered T cells modified with chimeric antigen receptors (CAR) for target recognition could now become a therapeutic option for some autoimmune diseases. Here, we review the ongoing developments with CAR T cells in the field of autoimmune disorders. We will cover first clinical results of applying anti-CD19 and anti-B cell maturation antigen CAR T cells for B cell elimination in systemic lupus erythematosus, refractory antisynthetase syndrome and myasthenia gravis, respectively. Furthermore, in preclinical models, researchers have also developed chimeric autoantibody receptor T cells that can eliminate individual B cell clones producing specific autoantibodies, and regulatory CAR T cells that do not eliminate autoreactive immune cells but dampen their wrong activation. Finally, we will address safety and manufacturing aspects for CAR T cells and discuss mRNA technologies and automation concepts for ensuring the future availability of safe and efficient CAR T cell products.
Topics: Humans; Immunotherapy, Adoptive; T-Lymphocytes; Receptors, Chimeric Antigen; Autoimmune Diseases
PubMed: 37996128
DOI: 10.1136/rmdopen-2022-002907 -
Autoimmunity Reviews Oct 2023Intermittent fasting, which includes periods of fasting and nutrition, has been considered a dietary approach for weight loss and metabolic health improvement. However,... (Review)
Review
Intermittent fasting, which includes periods of fasting and nutrition, has been considered a dietary approach for weight loss and metabolic health improvement. However, its potential benefits in autoimmune diseases have not been widely studied. This study aims to review the existing studies on the role and effects of intermittent fasting on autoimmune diseases. A comprehensive search was conducted on electronic databases such as PubMed, Scopus, Embase, and Web of Science, and relevant studies were included based on inclusion criteria. Studies show that intermittent fasting may have beneficial effects on various autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus, by reducing inflammatory markers, modulating the immune system, altering and improving gut microbiota, and enhancing cellular repair mechanisms through autophagy. However, evidence regarding the effects of intermittent fasting on other autoimmune diseases such as multiple sclerosis, systemic lupus erythematosus, thyroid diseases, and psoriasis is limited and inconclusive. Nevertheless, further research is needed to determine optimal intermittent fasting guidelines and its long-term effects on autoimmune diseases. Overall, this literature review proves intermittent fasting may be a promising dietary intervention for managing autoimmune diseases.
Topics: Humans; Intermittent Fasting; Autoimmune Diseases; Multiple Sclerosis; Lupus Erythematosus, Systemic; Arthritis, Rheumatoid
PubMed: 37572827
DOI: 10.1016/j.autrev.2023.103408 -
Critical Care (London, England) Dec 2023Observational studies have indicated a potential association between autoimmune diseases and the occurrence of sepsis, with an increased risk of mortality among affected... (Observational Study)
Observational Study
BACKGROUND
Observational studies have indicated a potential association between autoimmune diseases and the occurrence of sepsis, with an increased risk of mortality among affected patients. However, whether a causal relationship exists between the two remains unknown.
METHODS
In the Mendelian randomization (MR) study, we accessed exposure Genome-wide association study (GWAS) data from both the MRC Integrative Epidemiology Unit (MRC-IEU) and the FinnGen consortium. GWAS data for sepsis and its 28-day mortality were obtained from MRC-IEU. We employed univariable, multivariable, and reverse MR analyses to explore potential associations between autoimmune disorders and sepsis and its 28-day mortality. Additionally, a two-step mediation MR analysis was performed to investigate indirect factors possibly influencing the relationship between autoimmune disorders and sepsis. Afterward, we conducted an observational analysis to further explore the relationship between autoimmune disease and occurrence as well as 28-day mortality of sepsis using a real-world database (the MIMIC-IV database). A cohort of 2537 patients diagnosed with autoimmune disease were extracted from the database for analysis. Multivariable logistic regression models were used to confirm the association between autoimmune diseases and the occurrence of sepsis, as well as the 28-day mortality associated with sepsis.
RESULTS
In univariable MR analysis, there appeared to be causal relationships between genetically predicted type 1 diabetes (OR = 1.036, 95% CI = 1.023-1.048, p = 9.130E-09), rheumatoid arthritis (OR = 1.077, 95% CI = 1.058-1.097, p = 1.00E-15) and sepsis, while a potential causal link was observed between celiac disease and sepsis (OR = 1.013, 95% CI = 1.002-1.024, p = 0.026). In a subsequent multivariable MR analysis, only rheumatoid arthritis was found to be independently associated with the risk of sepsis (OR = 1.138, 95% CI = 1.044-1.240, p = 3.36E-03). Furthermore, there was no causal link between autoimmune disorders and 28-day mortality from sepsis. In reverse MR analysis, sepsis was suggested to potentially trigger the onset of psoriasis (OR = 1.084, 95% CI = 1.040-1.131, p = 1.488E-04). In the real-world observational study, adjusting for multiple confounders, rheumatoid arthritis (OR = 1.34, 95% CI = 1.11-1.64, p = 0.003) and multiple sclerosis (OR = 1.31, 95% CI = 1.03-1.68, p = 0.02) were associated with a higher risk of sepsis. In addition, we did not find that autoimmune diseases were associated with 28-day mortality from sepsis.
CONCLUSION
Both in observational and MR analysis, only rheumatoid arthritis is highly correlated with occurrence of sepsis. However, autoimmune disease was not associated with an increased 28-day mortality in patient with sepsis. Sepsis may increase the risk of developing psoriasis.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Autoimmune Diseases; Arthritis, Rheumatoid; Sepsis; Psoriasis
PubMed: 38053214
DOI: 10.1186/s13054-023-04763-5 -
Autoimmunity Reviews Jan 2024Fibromyalgia (FM) is a multifactorial syndrome which includes not only widespread pain and stiffness, now recognized as major symptoms, but also numerous other somatic,... (Review)
Review
Fibromyalgia (FM) is a multifactorial syndrome which includes not only widespread pain and stiffness, now recognized as major symptoms, but also numerous other somatic, emotional, and neuropsychic manifestation. The lack of specific validated biological and instrumental biomarkers has made FM a condition of unexplained medical significance, and its pathophysiology remains controversial and subject to debate. The current hypothesis regarding the pathogenesis of FM proposes that its development is influenced by various mechanism, including genetic predisposition, stressful life events, inflammatory processes, and cognitive-emotional factors. However, despite the extensive research conducted to date, the available data do not provide a clear understanding of the pathogenesis of FM. In this article, we report the opposing viewpoints of two leading experts who debate the question of whether FM is an autoimmune disease, based on scientific data regarding this condition. Both perspectives are discussed and the latest evidence on the pathophysiology of FM is reported to provide a comprehensive understanding of this complex syndrome.
Topics: Humans; Fibromyalgia; Syndrome; Biomarkers; Autoimmune Diseases; Genetic Predisposition to Disease
PubMed: 37634681
DOI: 10.1016/j.autrev.2023.103424 -
Rheumatology International Aug 2023Systemic lupus erythematosus (SLE) is a complex autoimmune disorder of unknown etiology. Multifactorial interaction among various susceptible factors such as... (Review)
Review
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder of unknown etiology. Multifactorial interaction among various susceptible factors such as environmental, hormonal, and genetic factors makes it more heterogeneous and complex. Genetic and epigenetic modifications have been realized to regulate the immunobiology of lupus through environmental modifications such as diet and nutrition. Although these interactions may vary from population to population, the understanding of these risk factors can enhance the perception of the mechanistic basis of lupus etiology. To recognize the recent advances in lupus, an electronic search was conducted among search engines such as Google Scholar and PubMed, where we found about 30.4% publications of total studies related to genetics and epigenetics, 33.5% publications related to immunobiology and 34% related to environmental factors. These outcomes suggested that management of diet and lifestyle have a direct relationship with the severity of lupus that influence via modulating the complex interaction among genetics and immunobiology. The present review emphasizes the knowledge about the multifactorial interactions between various susceptible factors based on recent advances that will further update the understanding of mechanisms involved in disease pathoetiology. Knowledge of these mechanisms will further assist in the creation of novel diagnostic and therapeutic options.
Topics: Humans; Lupus Erythematosus, Systemic; Autoimmune Diseases; Epigenesis, Genetic; Risk Factors
PubMed: 37226016
DOI: 10.1007/s00296-023-05346-x -
Frontiers in Immunology 2023Autoimmune bullous disease (AIBD) is a severe skin disorder caused by autoantibodies that target intercellular or cell-matrix adhesion proteins. Currently, the preferred... (Review)
Review
Autoimmune bullous disease (AIBD) is a severe skin disorder caused by autoantibodies that target intercellular or cell-matrix adhesion proteins. Currently, the preferred treatment for AIBD involves the use of glucocorticoids or traditional immunosuppressants. Additionally, the utilization of biological agents such as rituximab, omalizumab, and dupilumab is on the rise. However, effectively managing AIBD remains a challenge. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway has been implicated in various inflammatory diseases. In recent years, a range of drugs known as JAK inhibitors, which target this pathway, have been developed. Several studies have explored the efficacy and safety of JAK inhibitors for treating AIBD. Consequently, this review begins by examining the role of the JAK/STAT pathway in AIBD, summarizing the application of different JAK inhibitors in AIBD treatment, and emphasizing the importance of disease management in treating AIBD with JAK inhibitors. Furthermore, it highlights the need for a better understanding of the JAK/STAT pathway's role in AIBD, as well as the effectiveness and safety of JAK inhibitors for treating this disease.
Topics: Humans; Janus Kinase Inhibitors; Janus Kinases; STAT Transcription Factors; Signal Transduction; Autoimmune Diseases; Skin Diseases, Vesiculobullous
PubMed: 37492565
DOI: 10.3389/fimmu.2023.1220887 -
Journal of Neurology Aug 2023In 2015, we wrote a review in The Journal of Neurology summarizing the field of autoantibody-associated neurological diseases. Now, in 2023, we present an update of the...
In 2015, we wrote a review in The Journal of Neurology summarizing the field of autoantibody-associated neurological diseases. Now, in 2023, we present an update of the subject which reflects the rapid expansion and refinement of associated clinical phenotypes, further autoantibody discoveries, and a more detailed understanding of immunological and neurobiological pathophysiological pathways which mediate these diseases. Increasing awareness around distinctive aspects of their clinical phenotypes has been a key driver in providing clinicians with a better understanding as to how these diseases are best recognized. In clinical practice, this recognition supports the administration of often effective immunotherapies, making these diseases 'not to miss' conditions. In parallel, there is a need to accurately assess patient responses to these drugs, another area of growing interest. Feeding into clinical care are the basic biological underpinnings of the diseases, which offer clear pathways to improved therapies toward enhanced patient outcomes. In this update, we aim to integrate the clinical diagnostic pathway with advances in patient management and biology to provide a cohesive view on how to care for these patients in 2023, and the future.
Topics: Humans; Encephalitis; Autoantibodies; Hashimoto Disease; Autoimmune Diseases of the Nervous System
PubMed: 37115360
DOI: 10.1007/s00415-023-11685-3