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Frontiers in Immunology 2022Autoimmune disease, caused by unwanted immune responses to self-antigens, affects millions of people each year and poses a great social and economic burden to... (Review)
Review
Autoimmune disease, caused by unwanted immune responses to self-antigens, affects millions of people each year and poses a great social and economic burden to individuals and communities. In the course of autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, and multiple sclerosis, disturbances in the balance between the immune response against harmful agents and tolerance towards self-antigens lead to an immune response against self-tissues. In recent years, various regulatory immune cells have been identified. Disruptions in the quality, quantity, and function of these cells have been implicated in autoimmune disease development. Therefore, targeting or engineering these cells is a promising therapeutic for different autoimmune diseases. Regulatory T cells, regulatory B cells, regulatory dendritic cells, myeloid suppressor cells, and some subsets of innate lymphoid cells are arising as important players among this class of cells. Here, we review the roles of each suppressive cell type in the immune system during homeostasis and in the development of autoimmunity. Moreover, we discuss the current and future therapeutic potential of each one of these cell types for autoimmune diseases.
Topics: Humans; Immunity, Innate; Lymphocytes; Autoimmune Diseases; Autoimmunity; Autoantigens
PubMed: 36591309
DOI: 10.3389/fimmu.2022.1075813 -
International Journal of Molecular... Jul 2021Specific anti-tumor immune responses have proven to be pivotal in shaping tumorigenesis and tumor progression in solid cancers. These responses can also be of an... (Review)
Review
Specific anti-tumor immune responses have proven to be pivotal in shaping tumorigenesis and tumor progression in solid cancers. These responses can also be of an autoimmune nature, and autoantibodies can sometimes be present even before the onset of clinically overt disease. Autoantibodies can be generated due to mutated gene products, aberrant expression and post-transcriptional modification of proteins, a pro-immunogenic milieu, anti-cancer treatments, cross-reactivity of tumor-specific lymphocytes, epitope spreading, and microbiota-related and genetic factors. Understanding these responses has implications for both basic and clinical immunology. Autoantibodies in solid cancers can be used for early detection of cancer as well as for biomarkers of prognosis and treatment response. High-throughput techniques such as protein microarrays make parallel detection of multiple autoantibodies for increased specificity and sensitivity feasible, affordable, and quick. Cancer immunotherapy has revolutionized cancer treatments and has made a considerable impact on reducing cancer-associated morbidity and mortality. However, immunotherapeutic interventions such as immune checkpoint inhibition can induce immune-related toxicities, which can even be life-threatening. Uncovering the reasons for treatment-induced autoimmunity can lead to fine-tuning of cancer immunotherapy approaches to evade toxic events while inducing an effective anti-tumor immune response.
Topics: Animals; Autoantibodies; Autoimmunity; Biomarkers, Tumor; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasms
PubMed: 34360795
DOI: 10.3390/ijms22158030 -
Current Opinion in Endocrinology,... Aug 2021Current therapies for autoimmune disorders often employ broad suppression of the immune system. Antigen-specific immunotherapy (ASI) seeks to overcome the side-effects... (Review)
Review
PURPOSE OF REVIEW
Current therapies for autoimmune disorders often employ broad suppression of the immune system. Antigen-specific immunotherapy (ASI) seeks to overcome the side-effects of immunosuppressive therapy by specifically targeting only disease-related autoreactive T and B cells. Although it has been in development for several decades, ASI still is not in use clinically to treat autoimmunity. Novel ways to deliver antigen may be effective in inducing ASI. Here we review recent innovations in antigen delivery.
RECENT FINDINGS
New ways to deliver antigen include particle and nonparticle approaches. One main focus has been the targeting of antigen-presenting cells in a tolerogenic context. This technique often results in the induction and/or expansion of regulatory T cells, which has the potential to be effective against a complex, polyclonal immune response.
SUMMARY
Whether novel delivery approaches can help bring ASI into general clinical use for therapy of autoimmune diseases remains to be seen. However, preclinical work and early results from clinical trials using these new techniques show promising signs.
Topics: Antigens; Autoimmune Diseases; Autoimmunity; Humans; Immune Tolerance; Immunosuppressive Agents; Immunotherapy; T-Lymphocytes, Regulatory
PubMed: 34101653
DOI: 10.1097/MED.0000000000000649 -
Expert Reviews in Molecular Medicine Mar 2022Coronavirus disease 2019 (COVID-19) is associated with autoimmunity and systemic inflammation. Patients with autoimmune rheumatic and musculoskeletal disease (RMD) may... (Review)
Review
Coronavirus disease 2019 (COVID-19) is associated with autoimmunity and systemic inflammation. Patients with autoimmune rheumatic and musculoskeletal disease (RMD) may be at high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this review, based on evidence from the literature, as well as international scientific recommendations, we review the relationships between COVID-19, autoimmunity and patients with autoimmune RMDs, as well as the basics of a multisystemic inflammatory syndrome associated with COVID-19. We discuss the repurposing of pharmaceutics used to treat RMDs, the principles for the treatment of patients with autoimmune RMDs during the pandemic and the main aspects of vaccination against SARS-CoV-2 in autoimmune RMD patients.
Topics: Autoimmunity; COVID-19; Humans; Inflammation; Musculoskeletal Diseases; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35311631
DOI: 10.1017/erm.2022.10 -
Clinical and Experimental Immunology Jul 2022The human immune system safeguards against pathogens through a multitude of cellular and molecular signals, involving different components of the innate and adaptive... (Review)
Review
The human immune system safeguards against pathogens through a multitude of cellular and molecular signals, involving different components of the innate and adaptive response. Contrastingly, autoimmune diseases, allergic conditions, and cancer evoke different aspects of these otherwise protective processes. Understanding the immunological hallmarks for each pathological setting is essential for improving prevention, diagnosis, prognosis, and treatment. The activatory states of immune effector cells, especially in relation to their direct or indirect interactions with antibodies, are important determinants of an efficient, protective response that results in target clearance and improved clinical outcomes. Dysregulation of effector cells and their functions alongside alternatively activated humoral immune responses may contribute to several chronic diseases including allergic inflammation, autoimmune disorders and cancer. This Review Series brings to the forefront several key activation and regulatory features of immune effector cells in different diseases including cancer, infection allergy, and autoimmunity. Specific attention is drawn on how antibodies can impact effector cell states, and their pro-inflammatory and immune protective functions. Articles in this Series discuss different effector cells and antibody isotypes in infection, inflammation, tolerance and cancer immune surveillance, covering basic and translational mechanisms, clinical and epidemiological insights into these immune responses. Understanding the critical attributes of immune cells, especially those needed to effectively engage antibodies, will undoubtedly help better exploit their potential for disease management and therapy.
Topics: Autoimmune Diseases; Autoimmunity; Humans; Hypersensitivity; Immune Tolerance; Inflammation
PubMed: 35752999
DOI: 10.1093/cei/uxac065 -
Neurotherapeutics : the Journal of the... Jan 2021Associations between sleep disorders and neurological autoimmunity have been notably expanding recently. Potential immune-mediated etiopathogenesis has been proposed for... (Review)
Review
Associations between sleep disorders and neurological autoimmunity have been notably expanding recently. Potential immune-mediated etiopathogenesis has been proposed for various sleep disorders including narcolepsy, Kleine-Levin syndrome, and Morvan syndrome. Sleep manifestations are also common in various autoimmune neurological syndromes, but may be underestimated as overriding presenting (and potentially dangerous) neurological symptoms often require more urgent attention. Even so, sleep dysfunction has been described with various neural-specific antibody biomarkers, including IgLON5; leucine-rich, glioma-inactivated protein 1 (LGI1); contactin-associated protein 2 (CASPR2); N-methyl-D-aspartate (NMDA)-receptor; Ma2; dipeptidyl-peptidase-like protein-6 (DPPX); alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R); anti-neuronal nuclear antibody type-1 (ANNA-1, i.e., Hu); anti-neuronal nuclear antibody type-2 (ANNA-2, i.e., Ri); gamma-aminobutyric acid (GABA)-B-receptor (GABA-B-R); metabotropic glutamate receptor 5 (mGluR5); and aquaporin-4 (AQP-4). Given potentially distinctive findings, it is possible that sleep testing could potentially provide objective biomarkers (polysomnography, quantitative muscle activity during REM sleep, cerebrospinal fluid hypocretin-1) to support an autoimmune diagnosis, monitor therapeutic response, or disease progression/relapse. However, more comprehensive characterization of sleep manifestations is needed to better understand the underlying sleep disruption with neurological autoimmunity.
Topics: Autoimmune Diseases; Autoimmunity; Central Nervous System Diseases; Humans; Sleep Wake Disorders
PubMed: 33786802
DOI: 10.1007/s13311-021-01020-x -
Nature Reviews. Rheumatology Mar 2023The human genome project led to the advancement of genetic technologies and genomic medicine for a variety of human diseases, including monogenic autoimmune and... (Review)
Review
The human genome project led to the advancement of genetic technologies and genomic medicine for a variety of human diseases, including monogenic autoimmune and autoinflammatory diseases. As a result, the genome of an individual can now be rapidly sequenced at a low cost, and this technology is beginning to change the practice of rheumatology. In this Perspective, we describe how new sequencing technologies combined with careful clinical phenotyping have led to the discovery of rare rheumatic diseases and their corresponding disease-causing mutations. Additionally, we explore ways in which single-gene mutations, including somatic mutations, are creating opportunities to develop personalized medicines. To illustrate this idea, we focus on diseases affecting the TREX1-cGAS-STING pathway, which is associated with monogenic autoinflammatory diseases and vasculopathies. For many of the affected patients and families, there is an urgent, unmet need for the development of personalized therapies. New innovations related to small molecular inhibitors and gene therapies have the potential to benefit these families, and might help drive further innovations that could prove useful for patients with more common forms of autoimmunity and autoinflammation.
Topics: Humans; Inflammation; Precision Medicine; Autoimmunity; Hereditary Autoinflammatory Diseases; Autoimmune Diseases
PubMed: 36750685
DOI: 10.1038/s41584-022-00904-2 -
The Journal of Rheumatology Sep 2023Type I interferon (IFN-I) is thought to play a role in many systemic autoimmune diseases. IFN-I pathway activation is associated with pathogenic features, including the... (Review)
Review
Type I interferon (IFN-I) is thought to play a role in many systemic autoimmune diseases. IFN-I pathway activation is associated with pathogenic features, including the presence of autoantibodies and clinical phenotypes such as more severe disease with increased disease activity and damage. We will review the role and potential drivers of IFN-I dysregulation in 5 prototypic autoimmune diseases: systemic lupus erythematosus, dermatomyositis, rheumatoid arthritis, primary Sjögren syndrome, and systemic sclerosis. We will also discuss current therapeutic strategies that directly or indirectly target the IFN-I system.
Topics: Humans; Autoimmunity; Interferon Type I; Autoimmune Diseases; Lupus Erythematosus, Systemic; Interferons; Antibodies; Phenotype
PubMed: 37399470
DOI: 10.3899/jrheum.2022-0827 -
Best Practice & Research. Clinical... Feb 2020Links between autoimmune rheumatic diseases and cancer continue to be elucidated. In this review, we explore this complex, bidirectional relationship. First, the... (Review)
Review
Links between autoimmune rheumatic diseases and cancer continue to be elucidated. In this review, we explore this complex, bidirectional relationship. First, the increased risk of cancer across the breadth of the autoimmune rheumatic diseases is described. The magnitude of risk and types of tumors seen can differ by the type of autoimmune disease, timing of disease course, and even clinical and laboratory features within a particular autoimmune disease, suggesting that targeted cancer screening strategies can be considered. Multiple mechanisms linking autoimmune rheumatic diseases and cancer are discussed, including the development of autoimmunity in the context of naturally occurring anti-tumor immune responses and malignancy arising in the context of inflammation and damage from autoimmunity. Immunosuppression for rheumatic disease can increase risk for certain types of cancers. Finally, immune checkpoint inhibitors, a type of cancer immunotherapy, which cause a variety of inflammatory syndromes of importance to rheumatologists, are reviewed.
Topics: Autoimmune Diseases; Autoimmunity; Humans; Immunotherapy; Neoplasms; Rheumatic Diseases
PubMed: 32029389
DOI: 10.1016/j.berh.2019.101472 -
Frontiers in Immunology 2022The literature surrounding KLRG1 has primarily focused on NK and CD8 T cells. However, there is evidence that the most suppressive Tregs express KLRG1. Until now, the... (Review)
Review
The literature surrounding KLRG1 has primarily focused on NK and CD8 T cells. However, there is evidence that the most suppressive Tregs express KLRG1. Until now, the role of KLRG1 on Tregs has been mostly overlooked and remains to be elucidated. Here we review the current literature on KLRG1 with an emphasis on the KLRG1 Treg subset role during cancer development and autoimmunity. KLRG1 has been recently proposed as a new checkpoint inhibitor target, but these studies focused on the effects of KLRG1 blockade on effector cells. We propose that when designing anti-tumor therapies targeting KLRG1, the effects on both effector cells and Tregs will have to be considered.
Topics: Autoimmunity; CD8-Positive T-Lymphocytes; T-Lymphocytes, Regulatory
PubMed: 35572605
DOI: 10.3389/fimmu.2022.894508