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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 -
Autoimmunity Reviews Jul 2023Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in more than 670 million infections and almost... (Review)
Review
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in more than 670 million infections and almost 7 million deaths globally. The emergence of numerous SARS-CoV-2 has heightened public concern regarding the future course of the epidemic. Currently, the SARS-CoV-2 Omicron variant has rapidly become globally dominant in the COVID-19 pandemic due to its high infectivity and immune evasion. Consequently, vaccination implementation is critically significant. However, growing evidence suggests that COVID-19 vaccination may cause new-onset autoimmune diseases, including autoimmune glomerulonephritis, autoimmune rheumatic diseases, and autoimmune hepatitis. Nevertheless, the causal relationship between COVID-19 vaccines and these autoimmune diseases remains to be demonstrated. In this review, we provide evidence that vaccination induces autoimmunity and summarize possible mechanisms of action, such as molecular mimicry, activation by bystanders, and adjuvants. Our objective is not to refute the importance of vaccines, but to raise awareness about the potential risks of COVID-19 vaccination. In fact, we believe that the benefits of vaccination far outweigh the possible risks and encourage people to get vaccinated.
Topics: Humans; Autoimmune Diseases; COVID-19; COVID-19 Vaccines; Hepatitis, Autoimmune; Pandemics; SARS-CoV-2; Vaccination
PubMed: 37075917
DOI: 10.1016/j.autrev.2023.103340 -
Neurologic Clinics Feb 2024Aquaporin-4-IgG positive neuromyelitis optica spectrum disorder (AQP4+NMOSD) and myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are... (Review)
Review
Aquaporin-4-IgG positive neuromyelitis optica spectrum disorder (AQP4+NMOSD) and myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are antibody-associated diseases targeting astrocytes and oligodendrocytes, respectively. Their recognition as distinct entities has led to each having its own diagnostic criteria that require a combination of clinical, serologic, and MRI features. The therapeutic approach to acute attacks in AQP4+NMOSD and MOGAD is similar. There is now class 1 evidence to support attack-prevention medications for AQP4+NMOSD. MOGAD lacks proven treatments although clinical trials are now underway. In this review, we will outline similarities and differences between AQP4+NMOSD and MOGAD in terms of diagnosis and treatment.
Topics: Humans; Myelin-Oligodendrocyte Glycoprotein; Immunoglobulin G; Autoantibodies; Neuromyelitis Optica; Aquaporin 4; Central Nervous System Diseases; Central Nervous System
PubMed: 37980124
DOI: 10.1016/j.ncl.2023.06.009 -
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 -
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 -
European Journal of Medical Research Sep 2023IgA nephropathy (IgAN) is the most common primary glomerular disease in the world, and up to 40% of patients with IgAN develop end-stage renal disease (ESRD). At... (Review)
Review
IgA nephropathy (IgAN) is the most common primary glomerular disease in the world, and up to 40% of patients with IgAN develop end-stage renal disease (ESRD). At present, an increasing amount of evidence indicates that the pathogenesis of IgAN is related to autoimmunity. In recent years, several studies have shown that B cell activating factors (BAFF), also known as B lymphocyte stimulators (BLyS), and proliferation-inducing ligand APRIL are extremely important for the activation of autoimmune signalling pathways, which have become key targets for the treatment of IgAN. As a dual-target biological agent, telitacicept can inhibit both BLyS and APRIL cytokines, improve the function of renal immune complexes, and reduce haematuria and proteinuria, which play important roles in IgAN pathogenesis and long-term prognosis. This article reviews the role of telitacicept in IgA nephropathy and discusses its potential for use in the treatment of IgAN and other autoimmune diseases where pathogenesis is driven by B cells.
Topics: Humans; Glomerulonephritis, IGA; Kidney; Autoimmune Diseases; Kidney Glomerulus
PubMed: 37737205
DOI: 10.1186/s40001-023-01320-2 -
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 -
Science China. Life Sciences Jul 2023With the exception of an extremely small number of cases caused by single gene mutations, most autoimmune diseases result from the complex interplay between... (Review)
Review
With the exception of an extremely small number of cases caused by single gene mutations, most autoimmune diseases result from the complex interplay between environmental and genetic factors. In a nutshell, etiology of the common autoimmune disorders is unknown in spite of progress elucidating certain effector cells and molecules responsible for pathologies associated with inflammatory and tissue damage. In recent years, population genetics approaches have greatly enriched our knowledge regarding genetic susceptibility of autoimmunity, providing us with a window of opportunities to comprehensively re-examine autoimmunity-associated genes and possible pathways. In this review, we aim to discuss etiology and pathogenesis of common autoimmune disorders from the perspective of human genetics. An overview of the genetic basis of autoimmunity is followed by 3 chapters detailing susceptibility genes involved in innate immunity, adaptive immunity and inflammatory cell death processes respectively. With such attempts, we hope to expand the scope of thinking and bring attention to lesser appreciated molecules and pathways as important contributors of autoimmunity beyond the 'usual suspects' of a limited subset of validated therapeutic targets.
Topics: Humans; Autoimmune Diseases; Immunity, Innate; Autoimmunity; Adaptive Immunity; Genetic Predisposition to Disease
PubMed: 36738430
DOI: 10.1007/s11427-021-2187-3