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JCI Insight Jul 2023B cells contribute to multiple aspects of autoimmune disorders, and B cell-targeting therapies, including B cell depletion, have been proven to be efficacious in...
B cells contribute to multiple aspects of autoimmune disorders, and B cell-targeting therapies, including B cell depletion, have been proven to be efficacious in treatment of multiple autoimmune diseases. However, the development of novel therapies targeting B cells with higher efficacy and a nondepleting mechanism of action is highly desirable. Here we describe a nondepleting, high-affinity anti-human CD19 antibody LY3541860 that exhibits potent B cell inhibitory activities. LY3541860 inhibits B cell activation, proliferation, and differentiation of primary human B cells with high potency. LY3541860 also inhibits human B cell activities in vivo in humanized mice. Similarly, our potent anti-mCD19 antibody also demonstrates improved efficacy over CD20 B cell depletion therapy in multiple B cell-dependent autoimmune disease models. Our data indicate that anti-CD19 antibody is a highly potent B cell inhibitor that may have potential to demonstrate improved efficacy over currently available B cell-targeting therapies in treatment of autoimmune conditions without causing B cell depletion.
Topics: Mice; Animals; B-Lymphocytes; Antigens, CD19; Autoimmune Diseases
PubMed: 37427592
DOI: 10.1172/jci.insight.166137 -
Frontiers in Immunology 2024Excessive activation of immune cells by environmental factors, such as infection or individual genetic risk, causes various autoimmune diseases. species are... (Review)
Review
Excessive activation of immune cells by environmental factors, such as infection or individual genetic risk, causes various autoimmune diseases. species are gram-positive bacteria that colonize the nasopharynx, respiratory tract, gastrointestinal tract, genitourinary tract, and skin. Group A (GAS) species cause various symptoms, ranging from mild infections, such as tonsillitis and pharyngitis, to serious infections, such as necrotizing fasciitis and streptococcal toxic shock syndrome. The contribution of GAS infections to several autoimmune diseases, including acute rheumatic fever, vasculitis, and neuropsychiatric disorders, has been studied. In this review, we focus on the association between streptococcal infections and autoimmune diseases, and discuss current research on the mechanisms underlying the initiation and progression of autoimmune diseases.
Topics: Humans; Streptococcal Infections; Rheumatic Fever; Streptococcus pyogenes; Pharyngitis; Autoimmune Diseases
PubMed: 38464518
DOI: 10.3389/fimmu.2024.1361123 -
Hormone and Metabolic Research =... Dec 2023The human microbiome plays an integral role in health. In particular, it is important for the development, differentiation, and maturation of the immune system, 70% of... (Review)
Review
The human microbiome plays an integral role in health. In particular, it is important for the development, differentiation, and maturation of the immune system, 70% of which resides in the intestinal mucosa. Microbiome studies conducted to date have revealed an association between disturbances in the microbiota (dysbiosis) and various pathological disorders, including changes in host immune status. Autoimmune thyroid diseases are one of the most common organ-specific autoimmune disorders, with a worldwide prevalence higher than 5%. The predominant autoimmune thyroid diseases are Hashimoto's thyroiditis and Grave's disease. Several factors, such as genetic and environmental ones, have been studied. In accordance with recent studies, it is assumed that the gut microbiome might play a significant role in triggering autoimmune diseases of the thyroid gland. However, the exact etiology has not yet been elucidated. The present review aims to describe the work carried out so far regarding the role of gut microflora in the pathogenesis of autoimmune thyroid diseases and its involvement in the appearance of benign nodules and papillary thyroid cancer. It appears that future work is needed to elucidate more precisely the mechanism for gut microbiota involvement in the development of autoimmune thyroid diseases.
Topics: Humans; Gastrointestinal Microbiome; Thyroid Diseases; Hashimoto Disease; Autoimmune Diseases; Thyroid Neoplasms
PubMed: 37820693
DOI: 10.1055/a-2190-3847 -
Arthritis Research & Therapy Feb 2024Sjögren's disease is a heterogeneous autoimmune disorder that may be associated with systemic manifestations such as pulmonary or articular involvement. Systemic... (Review)
Review
Sjögren's disease is a heterogeneous autoimmune disorder that may be associated with systemic manifestations such as pulmonary or articular involvement. Systemic complications have prognostic implications and need to be identified and managed in a timely manner. Treatment should be tailored to the type and severity of organ involvement, ideally based on multidisciplinary evaluation.
Topics: Humans; Sjogren's Syndrome; Autoimmune Diseases
PubMed: 38331820
DOI: 10.1186/s13075-024-03262-4 -
Frontiers in Immunology 2023IgG4-related digestive diseases encompass a group of chronic inflammatory disorders characterized by autoimmune reactions and fibrosis affecting multiple digestive... (Review)
Review
IgG4-related digestive diseases encompass a group of chronic inflammatory disorders characterized by autoimmune reactions and fibrosis affecting multiple digestive organs. These diseases are identified by elevated serum levels of IgG4 and the presence of IgG4-positive plasma cell infiltration in the affected sites, along with storiform fibrosis, obliterative phlebitis, and eosinophilic infiltration. Although extensive research has been conducted, a comprehensive understanding of these conditions remains elusive. Current clinical diagnosis often relies on the application of integrated diagnostic criteria for IgG4-related diseases, combined with specific organ involvement criteria. Distinguishing them from malignancies poses considerable challenges. Moreover, further investigations are required to elucidate the underlying pathogenic mechanisms and explore potential therapeutic interventions. This review provides a systematic classification of IgG4-related digestive diseases while discussing their diagnostic strategies, clinical presentations, and treatment modalities. The comprehensive insights shared herein aim to guide clinicians in their practice and contribute to the advancement of knowledge in this field.
Topics: Humans; Autoimmune Diseases; Immunoglobulin G4-Related Disease; Immunoglobulin G; Diagnosis, Differential; Fibrosis
PubMed: 37868965
DOI: 10.3389/fimmu.2023.1278332 -
Best Practice & Research. Clinical... Dec 2023Autoimmune liver diseases (AILDs) are complex diseases with unknown causes and immune-mediated pathophysiology. In primary biliary cholangitis (PBC) and autoimmune... (Review)
Review
Autoimmune liver diseases (AILDs) are complex diseases with unknown causes and immune-mediated pathophysiology. In primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) disease modifying drugs are available which improve patient quality and quantity of life. In primary sclerosing cholangitis (PSC) no medical therapy is available and the only accepted treatment is liver transplantation (LT). PBC, PSC and AIH possess features that describe the archetype of patients within each disorder. On the other hand, the classical disorders are not homogeneous, and patients within each diagnosis may present with a range of clinical, biochemical, serological, and histological findings. Singularly, they are considered rare diseases, but together, they account for approximately 20% of LTs in Europe and USA. Management of these patients is complex, as AILDs are relatively uncommon in clinical practice with challenges in developing expertise, disease presentation can be sneaky, clinical phenotypes and disease course are heterogeneous. Prognostic models are key tools for clinicians to assess patients' risk and to provide personalized care to patients. Aim of this review is to discuss challenges of the management of AILDs and how the available prognostic models can help. We will discuss the prognostic models developed in AILDs, with a special focus on the prognostic models that can support the clinical management of patients with AILDs: in PBC models based on ursodeoxycholic acid (UDCA) response and markers of liver fibrosis; in PSC several markers including biochemistry, disease stage and radiological semiquantitative markers; and finally in AIH, markers of disease stage and disease activity.
Topics: Humans; Prognosis; Liver Cirrhosis, Biliary; Cholangitis, Sclerosing; Liver Diseases; Autoimmune Diseases; Hepatitis, Autoimmune
PubMed: 38103932
DOI: 10.1016/j.bpg.2023.101878 -
Frontiers in Immunology 2023Idiopathic inflammatory myopathies (IIMs) are common autoimmune diseases that affect skeletal muscle quality and function. The lack of an early diagnosis and treatment... (Review)
Review
Idiopathic inflammatory myopathies (IIMs) are common autoimmune diseases that affect skeletal muscle quality and function. The lack of an early diagnosis and treatment can lead to irreversible muscle damage. Non-coding RNAs (ncRNAs) play an important role in inflammatory transfer, muscle regeneration, differentiation, and regulation of specific antibody levels and pain in IIMs. ncRNAs can be detected in blood and hair; therefore, ncRNAs detection has great potential for diagnosing, preventing, and treating IIMs in conjunction with other methods. However, the specific roles and mechanisms underlying the regulation of IIMs and their subtypes remain unclear. Here, we review the mechanisms by which micro RNAs and long non-coding RNA-messenger RNA networks regulate IIMs to provide a basis for ncRNAs use as diagnostic tools and therapeutic targets for IIMs.
Topics: Humans; Myositis; RNA, Untranslated; Autoimmune Diseases; MicroRNAs; Muscle, Skeletal
PubMed: 37744337
DOI: 10.3389/fimmu.2023.1227945 -
Journal of the American Academy of... Oct 2023Data on the association between the development of autoimmune diseases and COVID-19 vaccination are limited.
BACKGROUND
Data on the association between the development of autoimmune diseases and COVID-19 vaccination are limited.
OBJECTIVE
To investigate the incidence and risk of autoimmune connective tissue disorders following mRNA-based COVID-19 vaccination.
METHODS
This nationwide population-based study was conducted in South Korea. Individuals who received vaccination between September 8, 2020-December 31, 2021, were identified. Historical prepandemic controls were matched for age and sex in 1:1 ratio. The incidence rate and risk of disease outcomes were compared.
RESULTS
A total of 3,838,120 vaccinated individuals and 3,834,804 controls without evidence of COVID-19 were included. The risk of alopecia areata, alopecia totalis, primary cicatricial alopecia, psoriasis, vitiligo, anti-neutrophil cytoplasmic antibody-associated vasculitis, sarcoidosis, Behcet disease, Crohn disease, ulcerative colitis, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren syndrome, ankylosing spondylitis, dermato/polymyositis, and bullous pemphigoid was not significantly higher in vaccinated individuals than in controls. The risk was comparable according to age, sex, type of mRNA-based vaccine, and cross-vaccination status.
LIMITATIONS
Possible selection bias and residual confounders.
CONCLUSION
These findings suggest that most autoimmune connective tissue disorders are not associated with a significant increase in risk. However, caution is necessary when interpreting results for rare outcomes due to limited statistical power.
Topics: Humans; COVID-19 Vaccines; COVID-19; Autoimmune Diseases; Connective Tissue Diseases; Alopecia Areata; Vaccination; Connective Tissue
PubMed: 37187424
DOI: 10.1016/j.jaad.2023.05.017 -
Advanced Drug Delivery Reviews Dec 2023The high prevalence and rising incidence of autoimmune diseases have become a prominent public health issue. Autoimmune disorders result from the immune system... (Review)
Review
The high prevalence and rising incidence of autoimmune diseases have become a prominent public health issue. Autoimmune disorders result from the immune system erroneously attacking the body's own healthy cells and tissues, causing persistent inflammation, tissue injury, and impaired organ function. Existing treatments primarily rely on broad immunosuppression, leaving patients vulnerable to infections and necessitating lifelong treatments. To address these unmet needs, an emerging frontier of vaccine development aims to restore immune equilibrium by inducing immune tolerance to autoantigens, offering a potential avenue for a cure rather than mere symptom management. We discuss this burgeoning field of vaccine development against inflammation and autoimmune diseases, with a focus on common autoimmune disorders, including multiple sclerosis, type 1 diabetes, rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus. Vaccine-based strategies provide a new pathway for the future of autoimmune disease therapeutics, heralding a new era in the battle against inflammation and autoimmunity.
Topics: Humans; Autoimmune Diseases; Lupus Erythematosus, Systemic; Autoimmunity; Immune Tolerance; Inflammation; Vaccines
PubMed: 37980949
DOI: 10.1016/j.addr.2023.115140 -
Medicina (Kaunas, Lithuania) Sep 2023Primary Sjögren's syndrome (pSS) is a heterogeneous chronic autoimmune disorder with multiple clinical manifestations that can develop into non-Hodgkin's lymphoma in... (Review)
Review
Primary Sjögren's syndrome (pSS) is a heterogeneous chronic autoimmune disorder with multiple clinical manifestations that can develop into non-Hodgkin's lymphoma in mucosa-associated lymphoid tissue. The pathogenesis of Sjögren's syndrome (SS) is not completely understood, but it is assumed that pathogenesis of SS is multifactorial. The microbiota plays a notable role in the development of autoimmune disorders, including Sjögren's syndrome. Molecular mimicry, metabolite changes and epithelial tolerance breakdown are pathways that might help to clarify the potential contribution of the microbiota to SS pathogenesis. This review aims to provide an overview of recent studies describing microbiota changes and microbiota mechanisms associated with Sjögren's syndrome. Data on the microbiota in SS from PubMed, Web of Science, Scopus and the Cochrane Library databases are summarized. Overall, the microbiota makes a major contribution to the development of Sjögren's syndrome and progression. Future microbiota studies should improve the management of this heterogeneous autoimmune disease.
Topics: Humans; Sjogren's Syndrome; Autoimmune Diseases; Databases, Factual; Microbiota
PubMed: 37763780
DOI: 10.3390/medicina59091661