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Anti-cytokine autoantibodies (ACAAs) are increasingly recognized as modulating disease severity in infection, inflammation and autoimmunity. By reducing or augmenting cytokine signalling pathways or by altering the half-life of cytokines in the circulation, ACAAs can be either pathogenic or disease ameliorating. The origins of ACAAs remain unclear. Here, we focus on the most common ACAAs in the context of disease groups with similar characteristics. We review the emerging genetic and environmental factors that are thought to drive their production. We also describe how the profiling of ACAAs should be considered for the early diagnosis, active monitoring, treatment or sub-phenotyping of diseases. Finally, we discuss how understanding the biology of naturally occurring ACAAs can guide therapeutic strategies., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The role of infections in the pathogenesis of autoimmune diseases has long been recognized and reported. In addition to infectious agents, the internal composition of the "friendly" living bacteria, (microbiome) and its correlation to immune balance and dysregulation have drawn the attention of researchers for decades. Nevertheless, only recently, scientific papers regarding the potential role of transferring microbiome from healthy donor subjects to patients with autoimmune diseases has been proposed. Fecal microbiota transplantation or FMT, carries the logic of transferring microorganisms responsible for immune balance from healthy donors to individuals with immune dysregulation or more accurately for our paper, autoimmune diseases. Viewing the microbiome as a pathogenetic player allows us to consider FMT as a pathogenetic-based treatment. Promising results alongside improved outcomes have been demonstrated in patients with different autoimmune diseases following FMT. Therefore, in our current extensive review, we aimed to highlight the implication of FMT in various autoimmune diseases, such as inflammatory bowel disease, autoimmune thyroid and liver diseases, systemic lupus erythematosus, and type 1 diabetes mellitus, among others. Presenting all the aspects of FMT in more than 12 autoimmune diseases in one paper, to the best of our knowledge, is the first time presented in medical literature. Viewing FMT as such could contribute to better understanding and newer application of the model in the therapy of autoimmune diseases, indeed. [ABSTRACT FROM AUTHOR]

There has been a steep increase in allergic and autoimmune diseases, reaching epidemic proportions and now affecting more than one billion people worldwide. These diseases are more common in industrialized countries, and their prevalence continues to rise in developing countries in parallel to urbanization and industrialization. Intact skin and mucosal barriers are crucial for the maintenance of tissue homeostasis as they protect host tissues from infections, environmental toxins, pollutants and allergens. A defective epithelial barrier has been demonstrated in allergic and autoimmune conditions such as asthma, atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, coeliac disease and inflammatory bowel disease. In addition, leakiness of the gut epithelium is also implicated in systemic autoimmune and metabolic conditions such as diabetes, obesity, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and autoimmune hepatitis. Finally, distant inflammatory responses due to a 'leaky gut' and microbiome changes are suspected in Alzheimer disease, Parkinson disease, chronic depression and autism spectrum disorders. This article introduces an extended 'epithelial barrier hypothesis', which proposes that the increase in epithelial barrier-damaging agents linked to industrialization, urbanization and modern life underlies the rise in allergic, autoimmune and other chronic conditions. Furthermore, it discusses how the immune responses to dysbiotic microbiota that cross the damaged barrier may be involved in the development of these diseases., (© 2021. Springer Nature Limited.)

Autoimmune diseases have a prevalence of approximately 7 to 9% and are classified as either organ-specific diseases, including type I diabetes, multiple sclerosis, inflammatory bowel disease and myasthenia gravis, or systemic diseases, including systemic lupus erythematosus, rheumatoid arthritis and Sjögren's syndrome. While many advancements have been made in understanding of the mechanisms of autoimmune disease, including the nature of self-tolerance and its breakdown, there remain unmet needs in terms of effective and highly targeted treatments. T regulatory cells (Tregs) are key mediators of peripheral tolerance and are implicated in many autoimmune diseases, either as a result of reduced numbers or altered function. Tregs may be broadly divided into those generated in the thymus (tTregs) and those generated in the periphery (pTregs). Tregs target many different immune cell subsets and tissues to suppress excessive inflammation and to support tissue repair and homeostasis: there is a fine balance between Treg cell stability and the plasticity that is required to adjust Tregs' regulatory purposes to particular immune responses. The central role of immunoglobulin E (IgE) in allergic disease is well recognized, and it is becoming increasingly apparent that this immunoglobulin also has a wider role encompassing other diseases including autoimmune disease. Anti-IgE treatment restores the capacity of plasmacytoid dendritic cells (pDCs) impaired by IgE- high-affinity IgE receptor (FcεR1) cross-linking to induce Tregs in vitro in atopic patients. The finding that anti-IgE therapy restores Treg cell homeostasis, and that this mechanism is associated with clinical improvement in asthma and chronic spontaneous urticaria suggests that anti-IgE therapy may also have a potential role in the treatment of autoimmune diseases in which Tregs are involved., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Long COVID, now unmistakably identified as a syndromic entity encompassing a complex spectrum of symptoms, demands immediate resolution of its elusive pathogenic underpinnings. The intricate interplay of diverse factors presents a complex puzzle, difficult to resolve, and thus poses a substantial challenge. As instances of long COVID manifest by repeated infections of SARS-CoV-2 and genetic predisposition, a detailed understanding in this regard is needed. This endeavor is a comprehensive exploration and analysis of the cascading pathogenetic events driven by viral persistence and replication. Beyond its morbidity, long COVID, more disabling than fatal, exacts one of the most substantial tolls on public health in contemporary times, with the potential to cripple national economies. The paper introduces a unified theory of long COVID, detailing a novel pathophysiological framework that interlinks persistent SARS-CoV-2 infection, autoimmunity, and systemic vascular pathology. We posit a model where viral reservoirs, immune dysregulation, and genetic predispositions converge to perpetuate disease. It challenges prevailing hypotheses with new evidence, suggesting innovative diagnostic and therapeutic approaches. The paper aims to shift the paradigm in long COVID research by providing an integrative perspective that encapsulates the multifaceted nature of the condition. We explain the immunological mechanisms, hypercoagulability states, and viral reservoirs in the skull that feed NeuroCOVID in patients with long COVID. Also, this study hints toward a patient approach and how to prioritize treatment sequences in long COVID patients in hospitals and clinics. [ABSTRACT FROM AUTHOR]

A comprehensive search of published literature in brain volumetry was conducted in three autoimmune diseases — systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and ulcerative colitis (UC) — with the intention of performing a meta-analysis of published data. Due to the lack of data in RA and UC, the reported meta-analysis was limited to SLE. The MEDLINE database was searched for studies from 1988 to March 2022. A total of 175 papers met the initial inclusion criteria, and 16 were included in a random-effects meta-analysis. The reduction in the number of papers included in the final analysis is primarily due to the lack of overlap in measured and reported brain regions. A significantly lower volume was seen in patients with SLE in the hippocampus, corpus callosum, and total gray matter volume measurements as compared to age- and sex-matched controls. There were not enough studies to perform a meta-analysis for RA and UC; instead, we include a summary of published volumetric studies. The meta-analyses revealed structural brain abnormalities in patients with SLE, suggesting that lower global brain volumes are associated with disease status. This volumetric difference was seen in both the hippocampus and corpus callosum and total gray matter volume measurements. These results indicate both gray and white matter involvements in SLE and suggest there may be both localized and global reductions in brain volume. [ABSTRACT FROM AUTHOR]

The use of animal models of human disease is critical for furthering our understanding of disease mechanisms, for the discovery of novel targets for treatment, and for translational research. This Special Topic entitled "Animal Models of Human Disease" aimed to collect state-of-the-art primary research studies and review articles from international experts and leading groups using animal models to study human diseases. Submissions were welcomed on a wide range of animal models and pathologies, including infectious disease, acute injury, regeneration, cancer, autoimmunity, degenerative and chronic disease. Seven participating MDPI journals supported the Special Topic, namely: Biomedicines, Cells, Current Issues in Molecular Biology, Diagnostics, Genes, the International Journal of Molecular Sciences, and the International Journal of Translational Medicine. In total, 46 papers were published in this Special Topic, with 37 full length original research papers, 2 research communications and 7 reviews. These contributions cover a wide range of clinically relevant, translatable, and comparative animal models, as well as furthering understanding of fundamental sciences, covering topics on physiological processes, on degenerative, inflammatory, infectious, autoimmune, neurological, metabolic, heamatological, hormonal and mitochondrial disorders, developmental processes and diseases, cardiology, cancer, trauma, stress, and ageing. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the loss of dopaminergic neurons and neuroinflammation. Recent studies have identified a role of T cells in the pathogenesis of PD. Additionally, these studies suggested that α-synuclein (α-Syn) is related to abnormal T-cell responses and may act as an epitope and trigger autoimmune T-cell responses. However, it is unclear whether the α-Syn-mediated autoimmune response occurs and whether it is related to neuronal cell death and glial cell activation. In this study, we investigated the autoimmune T-cell response induced by α-Syn peptides and evaluated the neurotoxic effect of the α-Syn peptide-mediated autoimmune response. The immunization of mice with α-Syn peptides resulted in enhanced autoimmune responses, such as the peptide recall response, polarization toward Th1/Th17 cells, and regulatory T cell imbalance. Furthermore, the α-Syn autoimmune response led to the death of primary neurons cocultured with splenocytes. Treatment with conditioned media from α-Syn peptide-immunized splenocytes induced microglia and toxic A1-type astrocyte activation. Taken together, our results provide evidence of the potential role of the α-Syn-initiated autoimmune response and its contribution to neuronal cell death and glial cell activation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Autoimmune diseases are burdensome conditions that affect a significant fraction of the global population. The hallmark of autoimmune disease is a host's immune system being licensed to attack its tissues based on specific antigens. There are no cures for autoimmune diseases. The current clinical standard for treating autoimmune diseases is the administration of immunosuppressants, which weaken the immune system and reduce auto-inflammatory responses. However, people living with autoimmune diseases are subject to toxicity, fail to mount a sufficient immune response to protect against pathogens, and are more likely to develop infections. Therefore, there is a concerted effort to develop more effective means of targeting immunomodulatory therapies to antigen-presenting cells, which are involved in modulating the immune responses to specific antigens. In this review, we highlight approaches that are currently in development to target antigen-presenting cells and improve therapeutic outcomes in autoimmune diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Orthostatic hypotension (OH) is a common condition. Many potential etiologies of OH have been identified, but in clinical practice the underlying cause of OH is often unknown. In the present study, we identified a novel and extraordinary etiology of OH. We describe a first case of acquired severe OH with syncope, and the female patient had extremely low levels of catecholamines and serotonin in plasma, urine and cerebrospinal fluid (CSF). Her clinical and biochemical evidence showed a deficiency of the enzyme aromatic l-amino acid decarboxylase (AADC), which converts l-DOPA to dopamine, and 5-hydroxytryptophan to serotonin, respectively. The consequence of pharmacologic stimulation of catecholaminergic nerves and radionuclide examination revealed her catecholaminergic nerves denervation. Moreover, we found that the patient's serum showed presence of autoantibodies against AADC, and that isolated peripheral blood mononuclear cells (PBMCs) from the patient showed cytokine-induced toxicity against AADC. These observations suggest that her autoimmunity against AADC is highly likely to cause toxicity to adrenal medulla and catecholaminergic nerves which contain AADC, resulting in hypocatecholaminemia and severe OH. Administration of vitamin B6, an essential cofactor of AADC, enhanced her residual AADC activity and drastically improved her symptoms. Our data thus provide a new insight into pathogenesis and pathophysiology of OH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

High myopia is a leading cause of blindness worldwide, among which pathologic myopia, characterized by typical myopic macular degeneration, is the most detrimental. However, its pathogenesis remains largely unknown. Here, using a HuProt array, we first initiated a serological autoantibody profiling of high myopia and identified 18 potential autoantibodies, of which anti-LIMS1 autoantibody was validated by a customized focused microarray. Further subgroup analysis revealed its actual relevance to pathologic myopia, rather than simple high myopia without myopic macular degeneration. Mechanistically, anti-LIMS1 autoantibody predominantly belonged to IgG1/IgG2/IgG3 subclasses. Serum IgG obtained from patients with pathologic myopia could disrupt the barrier function of retinal pigment epithelial cells via cytoskeleton disorganization and tight junction component reduction, and also trigger a pro-inflammatory mediator cascade in retinal pigment epithelial cells, which were all attenuated by depletion of anti-LIMS1 autoantibody. Together, these data uncover a previously unrecognized autoimmune etiology of myopic macular degeneration in pathologic myopia., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Pre-capillary pulmonary arterial hypertension (PAH) is hemodynamically characterized by a mean pulmonary arterial pressure (mPAP) ≥ 20 mmHg, pulmonary capillary wedge pressure (PAWP) ≤15 mmHg and pulmonary vascular resistance (PVR) > 2. PAH is classified in six clinical subgroups, including idiopathic PAH (IPAH) and PAH associated to connective tissue diseases (CTD-PAH), that will be the main object of this review. The aim is to compare these two PAH subgroups in terms of epidemiology, histological and pathogenic findings in an attempt to define disease-specific features, including autoimmunity, that may explain the heterogeneity of response to therapy between IPAH and CTD-PAH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Renal fibrosis is now recognized as a main determinant of renal pathology to include chronic kidney disease. Deposition of pathological matrix in the walls of glomerular capillaries, the interstitial space, and around arterioles predicts and contributes to the functional demise of the nephron and its surrounding vasculature. The recent identification of the major cell populations of fibroblast precursors in the kidney interstitium such as pericytes and tissue-resident mesenchymal stem cells, or bone-marrow-derived macrophages, and in the glomerulus such as podocytes, parietal epithelial and mesangial cells, has enabled the study of the fibrogenic process thought the lens of involved immunological pathways. Besides, a growing body of evidence is supporting the role of the lymphatic system in modulating the immunological response potentially leading to inflammation and ultimately renal damage. These notions have moved our understanding of renal fibrosis to be recognized as a clinical entity and new main player in autoimmunity, impacting directly the management of patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

This document is an editorial published in the journal Frontiers in Immunology. It discusses the role of myeloid-derived suppressor cells (MDSCs) in various health conditions and diseases, including cancer, autoimmunity, pregnancy, neonates, and aging. The editorial highlights the complexity of MDSCs and their potential as targets for immunotherapy. It also presents five research papers that provide insights into the multifaceted roles of MDSCs in oncogenesis, maternal-fetal interface, and aging, contributing to a better understanding of MDSCs biology and the development of more effective immunotherapeutic approaches. [Extracted from the article]

T-cell-mediated autoimmune type 1 diabetes (T1D) is characterized by the immune-mediated destruction of pancreatic beta cells (b-cells). The increasing prevalence of T1D poses significant challenges to the healthcare system, particularly in countries with struggling economies. This review paper highlights the multifaceted roles of Peroxisome Proliferator-Activated Receptors (PPARs) in the context of T1D, shedding light on their potential as regulators of immune responses and b-cell biology. Recent research has elucidated the intricate interplay between CD4+ T cell subsets, such as Tregs and Th17, in developing autoimmune diseases like T1D. Th17 cells drive inflammation, while Tregs exert immunosuppressive functions, highlighting the delicate balance crucial for immune homeostasis. Immunotherapy has shown promise in reinstating self-tolerance and restricting the destruction of autoimmune responses, but further investigations are required to refine these therapeutic strategies. Intriguingly, PPARs, initially recognized for their role in lipid metabolism, have emerged as potent modulators of inflammation in autoimmune diseases, particularly in T1D. Although evidence suggests that PPARs affect the b-cell function, their influence on T-cell responses and their potential impact on T1D remains largely unexplored. It was noted that PPARa is involved in restricting the transcription of IL17A and enhancing the expression of Foxp3 by minimizing its proteasomal degradation. Thus, antagonizing PPARs may exert beneficial effects in regulating the differentiation of CD4+ T cells and preventing T1D. Therefore, this review advocates for comprehensive investigations to delineate the precise roles of PPARs in T1D pathogenesis, offering innovative therapeutic avenues that target both the immune system and pancreatic function. This review paper seeks to bridge the knowledge gap between PPARs, immune responses, and T1D, providing insights that may revolutionize the treatment landscape for this autoimmune disorder. Moreover, further studies involving PPAR agonists in non-obese diabetic (NOD) mice hold promise for developing novel T1D therapies. [ABSTRACT FROM AUTHOR]

The complicated relationships between autoimmunity, COVID-19, and COVID-19 vaccinations are described, giving insight into their intricacies. Antinuclear antibodies (ANA), anti-Ro/SSA, rheumatoid factor, lupus anticoagulant, and antibodies against interferon (IFN)-I have all been consistently found in COVID-19 patients, indicating a high prevalence of autoimmune reactions following viral exposure. Furthermore, the discovery of human proteins with structural similarities to SARS-CoV-2 peptides as possible autoantigens highlights the complex interplay between the virus and the immune system in initiating autoimmunity. An updated summary of the current status of COVID-19 vaccines is presented. We present probable pathways underpinning the genesis of COVID-19 autoimmunity, such as bystander activation caused by hyperinflammatory conditions, viral persistence, and the creation of neutrophil extracellular traps. These pathways provide important insights into the development of autoimmune-related symptoms ranging from organ-specific to systemic autoimmune and inflammatory illnesses, demonstrating the wide influence of COVID-19 on the immune system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Autoimmunity is a multifaceted disorder influenced by both genetic and environmental factors, and metal exposure has been implicated as a potential catalyst, especially in autoimmune diseases affecting the central nervous system. Notably, metals like mercury, lead, and aluminum exhibit well-established neurotoxic effects, yet the precise mechanisms by which they elicit autoimmune responses in susceptible individuals remain unclear. Recent studies propose that metal-induced autoimmunity may arise from direct toxic effects on immune cells and tissues, coupled with indirect impacts on the gut microbiome and the blood-brain barrier. These effects can activate self-reactive T cells, prompting the production of autoantibodies, inflammatory responses, and tissue damage. Diagnosing metal-induced autoimmunity proves challenging due to nonspecific symptoms and a lack of reliable biomarkers. Treatment typically involves chelation therapy to eliminate excess metals and immunomodulatory agents to suppress autoimmune responses. Prevention strategies include lifestyle adjustments to reduce metal exposure and avoiding occupational and environmental risks. Prognosis is generally favorable with proper treatment; however, untreated cases may lead to autoimmune disorder progression and irreversible organ damage, particularly in the brain. Future research aims to identify genetic and environmental risk factors, enhance diagnostic precision, and explore novel treatment approaches for improved prevention and management of this intricate and debilitating disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In order to understand autoimmune phenomena contributing to the pathophysiology of COVID-19 and post-COVID syndrome, we have been profiling autoantigens (autoAgs) from various cell types. Although cells share numerous autoAgs, each cell type gives rise to unique COVID-altered autoAg candidates, which may explain the wide range of symptoms experienced by patients with autoimmune sequelae of SARS-CoV-2 infection. Based on the unifying property of affinity between autoAgs and the glycosaminoglycan dermatan sulfate (DS), this paper reports 140 candidate autoAgs identified from proteome extracts of human Jurkat T-cells, of which at least 105 (75%) are known targets of autoantibodies. Comparison with currently available multi-omic COVID-19 data shows that 125 (89%) DS-affinity proteins are altered at protein and/or RNA levels in SARS-CoV-2-infected cells or patients, with at least 94 being known autoAgs in a wide spectrum of autoimmune diseases and cancer. Protein alterations by ubiquitination and phosphorylation during the viral infection are major contributors of autoAgs. The autoAg protein network is significantly associated with cellular response to stress, apoptosis, RNA metabolism, mRNA processing and translation, protein folding and processing, chromosome organization, cell cycle, and muscle contraction. The autoAgs include clusters of histones, CCT/TriC chaperonin, DNA replication licensing factors, proteasome and ribosome proteins, heat shock proteins, serine/arginine-rich splicing factors, 14-3-3 proteins, and cytoskeletal proteins. AutoAgs, such as LCP1 and NACA, that are altered in the T cells of COVID patients may provide insight into T-cell responses to viral infection and merit further study. The autoantigen-ome from this study contributes to a comprehensive molecular map for investigating acute, subacute, and chronic autoimmune disorders caused by SARS-CoV-2. Based on the unique affinity between autoantigens (autoAgs) and dermatan sulfate (DS), this paper reports 140 candidate autoAgs identified from proteome extracts of Jurkat T-cells, with at least 105 (75%) being known targets of autoantibodies in various autoimmune diseases and cancer. Comparison with currently available multi-omic COVID-19 data shows that 125 (89%) DS-affinity proteins are altered in SARS-CoV-2-infected cells or patients. AutoAgs, such as LCP1 and NACA, that are altered in the T cells of COVID-19 patients may provide insight into T-cell responses during viral infection. [ABSTRACT FROM AUTHOR]

To understand how COVID-19 may induce autoimmune diseases, we have been compiling an atlas of COVID autoantigens (autoAgs). Using dermatan sulfate (DS) affinity enrichment of autoantigenic proteins extracted from HS-Sultan lymphoblasts, we identified 362 DS-affinity proteins, of which at least 201 (56%) are confirmed autoAgs. Comparison with available multi-omic COVID data shows that 315 (87%) of the 362 proteins are affected in SARS-CoV-2 infection via altered expression, interaction with viral components, or modification by phosphorylation or ubiquitination, at least 186 (59%) of which are known autoAgs. These proteins are associated with gene expression, mRNA processing, mRNA splicing, translation, protein folding, vesicles, and chromosome organization. Numerous nuclear autoAgs were identified, including both classical antinuclear antibodies (ANAs) and extractable nuclear antigens (ENAs) of systemic autoimmune diseases and unique autoAgs involved in the DNA replication fork, mitotic cell cycle, or telomerase maintenance. We also identified many uncommon autoAgs involved in nucleic acid and peptide biosynthesis and nucleocytoplasmic transport, such as aminoacyl-tRNA synthetases. In addition, this study found autoAgs that potentially interact with multiple SARS-CoV-2 Nsp and Orf components, including CCT/TriC chaperonin, insulin degrading enzyme, platelet-activating factor acetylhydrolase, and the ezrin-moesin-radixin family. Furthermore, B-cell-specific IgM-associated endoplasmic reticulum (ER) complex (including MBZ1, BiP, heat shock proteins, and protein disulfide-isomerases) is enriched by DS-affinity and up-regulated in B-cells of COVID-19 patients, and a similar IgH-associated ER complex was also identified in autoreactive pre-B1 cells in our previous study, which suggests a role of autoreactive B1 cells in COVID-19 that merits further investigation. In summary, this study demonstrates that virally infected cells are characterized by alterations of proteins with propensity to become autoAgs, thereby providing a possible explanation for infection-induced autoimmunity. The COVID autoantigen-ome provides a valuable molecular resource and map for investigation of COVID-related autoimmune sequelae and considerations for vaccine design. This paper investigates the autoantigenic proteome ('autoantigen-ome') of human B cells and shows that a large fraction of these DS-binding autoantigens is affected during SARS-CoV-2 infection, giving rise to a diverse pool of autoAgs that may lead to infection-induced autoimmune diseases. The COVID autoantigen-ome provided in this paper may serve as a molecular map and resource for investigating autoimmune phenomena of SARS-CoV-2 infection and its long-term sequelae. Understanding immunogenic proteins of COVID may also enhance vaccine target design. [ABSTRACT FROM AUTHOR]

Relapsing polychondritis is a chronic autoimmune inflammatory condition characterized by recurrent episodes of inflammation at the level of cartilaginous structures and tissues rich in proteoglycans. The pathogenesis of the disease is complex and still incompletely elucidated. The data support the important role of a particular genetic predisposition, with HLA-DR4 being considered an allele that confers a major risk of disease occurrence. Environmental factors, mechanical, chemical or infectious, act as triggers in the development of clinical manifestations, causing the degradation of proteins and the release of cryptic cartilage antigens. Both humoral and cellular immunity play essential roles in the occurrence and perpetuation of autoimmunity and inflammation. Autoantibodies anti-type II, IX and XI collagens, anti-matrilin-1 and anti-COMPs (cartilage oligomeric matrix proteins) have been highlighted in increased titers, being correlated with disease activity and considered prognostic factors. Innate immunity cells, neutrophils, monocytes, macrophages, natural killer lymphocytes and eosinophils have been found in the perichondrium and cartilage, together with activated antigen-presenting cells, C3 deposits and immunoglobulins. Also, T cells play a decisive role in the pathogenesis of the disease, with relapsing polychondritis being considered a TH1-mediated condition. Thus, increased secretions of interferon γ, interleukin (IL)-12 and IL-2 have been highlighted. The "inflammatory storm" formed by a complex network of pro-inflammatory cytokines and chemokines actively modulates the recruitment and infiltration of various cells, with cartilage being a source of antigens. Along with RP, VEXAS syndrome, another systemic autoimmune disease with genetic determinism, has an etiopathogenesis that is still incompletely known, and it involves the activation of the innate immune system through different pathways and the appearance of the cytokine storm. The clinical manifestations of VEXAS syndrome include an inflammatory phenotype often similar to that of RP, which raises diagnostic problems. The management of RP and VEXAS syndrome includes common immunosuppressive therapies whose main goal is to control systemic inflammatory manifestations. The objective of this paper is to detail the main etiopathogenetic mechanisms of a rare disease, summarizing the latest data and presenting the distinct features of these mechanisms. [ABSTRACT FROM AUTHOR]

Paraneoplastic neurological syndromes (PNSs) are an uncommon complication of cancer, affecting nearby 1/10,000 subjects with a tumour. PNSs can involve all the central and peripheral nervous systems, the muscular system, and the neuromuscular junction, causing extremely variable symptomatology. The diagnosis of the paraneoplastic disease usually precedes the clinical manifestations of cancer, making an immediate recognition of the pathology crucial to obtain a better prognosis. PNSs are autoimmune diseases caused by the expression of common antigens by the tumour and the nervous system. Specific antibodies can help clinicians diagnose them, but unfortunately, they are not always detectable. Immunosuppressive therapy and the treatment of cancer are the cornerstones of therapy for PNSs. This paper reports a case of PNSs associated with breast tumours and focuses on the most common paraneoplastic neurological syndromes. We report a case of a young female with a clinical syndrome of the occurrence of rigidity in the right lower limb with postural instability with walking supported and diplopia, with a final diagnosis of paraneoplastic cerebellar degeneration and seronegative rigid human syndrome associated with infiltrating ductal carcinoma of the breast. [ABSTRACT FROM AUTHOR]

Background Despite the growing utilization of data-driven methods to investigate multimorbidity patterns, there is currently no consensus or guidance on the conditions to include when identifying patterns. This scoping review aims to systematically examine the nature of conditions included in existing studies using data-driven techniques. Methods A comprehensive search of three electronic databases (MEDLINE, Web of Science and Scopus) was conducted to identify relevant publications from inception to 28 February 2022 using predefined search terms and inclusion/exclusion criteria. The reference lists and citations of relevant papers were also searched. Results Among 7326 search results, 5444 relevant articles were identified. After screening against the eligibility criteria, 60 articles were included in the review. Half of the reviewed studies reported selection criteria for conditions, with prevalence in the population of interest being the most common criterion (40%). Most studies included at least one neurological [59 (98.3%)], musculoskeletal [58 (96.7%)], respiratory [57 (95.0%)] or mental health [56 (93.3%)] condition. In contrast, only a small proportion of studies included skin [17 (28.3%)], infections [14 (23.3%)] or autoimmune conditions [10 (16.7%)]. Nine conditions (hypertension, diabetes, cancer, arthritis, COPD, asthma, depression, stroke and osteoporosis) were included by more than half of the studies. Conclusions This review highlights the considerable heterogeneity among the conditions included in analyses of multimorbidity patterns. Researchers should provide a clear rationale for the selection of conditions to facilitate comparisons across studies and ensure reproducibility, as well as consider selecting a diverse range of conditions to capture the complexity of multimorbidity. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What are the similarities and differences in endometrial B cells in the normal human endometrium and benign reproductive pathologies? SUMMARY ANSWER Endometrial B cells typically constitute <5% of total endometrial CD45+ lymphocytes, and no more than 2% of total cells in the normal endometrium, and while their relative abundance and phenotypes vary in benign gynaecological conditions, current evidence is inconsistent. WHAT IS KNOWN ALREADY B cells are vitally important in the mucosal immune environment and have been extensively characterized in secondary lymphoid organs and tertiary lymphoid structures (TLSs), with the associated microenvironment germinal centre. However, in the endometrium, B cells are largely overlooked, despite the crucial link between autoimmunity and reproductive pathologies and the fact that B cells are present in normal endometrium and benign female reproductive pathologies, scattered or in the form of lymphoid aggregates (LAs). A comprehensive summary of current data investigating B cells will facilitate our understanding of endometrial B cells in the endometrial mucosal immune environment. STUDY DESIGN, SIZE, DURATION This systematic review retrieved relevant studies from four databases (MEDLINE, EMBASE, Web of Science Core Collection and CINAHL) from database inception until November 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS The search strategy combined the use of subject headings and relevant text words related to 'endometrium', 'B cells' and B-cell derivatives, such as 'antibody' and 'immunoglobulin'. Non-benign diseases were excluded using cancer-related free-text terms, and searches were limited to the English language and human subjects. Only peer-reviewed research papers were included. Each paper was graded as 'Good', 'Fair' or 'Poor' quality based on the NEWCASTLE-OTTAWA quality assessment scale. Only 'Good' quality papers were included. MAIN RESULTS AND THE ROLE OF CHANCE Twenty-seven studies met the selection criteria and were included in this review: 10 cross-sectional studies investigated B cells in the normal endometrium; and 17 case–control studies compared the characteristics of endometrial B cells in control and benign female reproductive pathologies including endometritis, endometriosis, infertility, abnormal uterine bleeding, endometrial polyps and uterine fibroids. In all studies, B cells were present in the endometrium, scattered or in the form of LAs. CD20+ B cells were more abundant in patients with endometritis, but the data were inconsistent as to whether B-cell numbers were increased in endometriosis and patients with reproductive pathologies. LIMITATIONS, REASONS FOR CAUTION Although only 'good' quality papers were included in this systematic review, there were variations in patients' age, diagnostic criteria for different diseases and sample collection time among included studies. Additionally, a large number of the included studies only used immunohistochemistry as the identification method for endometrial B cells, which may fail to provide an accurate representation of the numbers of endometrial B cells. WIDER IMPLICATIONS OF THE FINDINGS Histological studies found that endometrial B cells are either scattered or surrounded by T cells in LAs: the latter structure seems to be under hormonal control throughout the menstrual cycle and resembles TLSs that have been observed in other tissues. Further characterization of endometrial B cells and LAs could offer insights to endometrial B-cell function, particularly in the context of autoimmune-associated pathologies, such as endometriosis. Additionally, clinicians should be aware of the limited value of diagnosing plasma cell infiltration using only CD138. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by Finox Biotech. The authors have no conflicts of interest to declare. PROSPERO REGISTRATION NUMBER This systematic review was registered in PROSPERO in January 2020 (PROSPERO ID: CRD42020152915). [ABSTRACT FROM AUTHOR]

The field of medical research has been always full of innovation and huge leaps revolutionizing the scientific world. In the recent years, we have witnessed this firsthand by the evolution of Artificial Intelligence (AI), with ChatGPT being the most recent example. ChatGPT is a language chat bot which generates human-like texts based on data from the internet. If viewed from a medical point view, ChatGPT has shown capabilities of composing medical texts similar to those depicted by experienced authors, to solve clinical cases, to provide medical solutions, among other fascinating performances. Nevertheless, the value of the results, limitations, and clinical implications still need to be carefully evaluated. In our current paper on the role of ChatGPT in clinical medicine, particularly in the field of autoimmunity, we aimed to illustrate the implication of this technology alongside the latest utilization and limitations. In addition, we included an expert opinion on the cyber-related aspects of the bot potentially contributing to the risks attributed to its use, alongside proposed defense mechanisms. All of that, while taking into consideration the rapidity of the continuous improvement AI experiences on a daily basis., Competing Interests: Declaration of Competing Interest The authors decalre no conflict of interests., (Copyright © 2023. Published by Elsevier B.V.)

Background: The Environmental Determinants of Islet Autoimmunity (ENDIA) pregnancy-birth cohort investigates the developmental origins of type 1 diabetes (T1D), with recruitment between 2013 and 2019. ENDIA is the first study in the world with comprehensive data and biospecimen collection during pregnancy, at birth and through childhood from at-risk children who have a first-degree relative with T1D. Environmental exposures are thought to drive the progression to clinical T1D, with pancreatic islet autoimmunity (IA) developing in genetically susceptible individuals. The exposures and key molecular mechanisms driving this progression are unknown. Persistent IA is the primary outcome of ENDIA; defined as a positive antibody for at least one of IAA, GAD, ZnT8 or IA2 on two consecutive occasions and signifies high risk of clinical T1D. Method: A nested case-control (NCC) study design with 54 cases and 161 matched controls aims to investigate associations between persistent IA and longitudinal omics exposures in ENDIA. The NCC study will analyse samples obtained from ENDIA children who have either developed persistent IA or progressed to clinical T1D (cases) and matched control children at risk of developing persistent IA. Control children were matched on sex and age, with all four autoantibodies absent within a defined window of the case's onset date. Cases seroconverted at a median of 1.37 years (IQR 0.95, 2.56). Longitudinal omics data generated from approximately 16,000 samples of different biospecimen types, will enable evaluation of changes from pregnancy through childhood. Conclusions: This paper describes the ENDIA NCC study, omics platform design considerations and planned univariate and multivariate analyses for its longitudinal data. Methodologies for multivariate omics analysis with longitudinal data are discovery-focused and data driven. There is currently no single multivariate method tailored specifically for the longitudinal omics data that the ENDIA NCC study will generate and therefore omics analysis results will require either cross validation or independent validation. The ENDIA nested case-control study will utilize longitudinal omics data on approximately 16,000 samples from 190 unique children at risk of type 1 diabetes (T1D), including 54 who have developed islet autoimmunity (IA), followed during pregnancy, at birth and during early childhood, enabling the developmental origins of T1D to be explored. [ABSTRACT FROM AUTHOR]

If one had any doubts before the pandemic regarding the correlation between infections and autoimmunity, COVID-19 left us fascinated on the strong bond between the two entities. The immune and autoimmune reactions seen in patients infected with SARS-CoV-2 have served as a base for this assumption. Later on, the use of immunosuppressants such as systemic glucocorticoids, among other biological agents, turned this assumption to a fact. This was no different when it comes to the vaccines against COVID-19. Through several postulated mechanisms these vaccines, although generally considered safe, are thought to have the potential to result in autoimmune reactions making them not more innocent than the infection itself. When systemic lupus erythematous (SLE) is viewed as a classical autoimmune multisystemic disorder, the connection with SARS-CoV-2 infection and COVID-19 vaccination is of extreme importance. This is because early reports during the pandemic have shown increased rates of SARS-CoV-2 infection among patients known previously to have SLE and much more interestingly, cases of new-onset SLE after COVID-19 have been documented in the literature. Subsequently vaccines against COVID-19, those mRNA-based and adenovirus-vector based, were reported to induce new SLE cases, trigger immune thrombocytopenia or lupus nephritis, two common presentations of SLE, or exacerbate flares. In our paper, we concluded various aspects of available and recent data regarding SLE and COVID-19 as both an infection and vaccination. [ABSTRACT FROM AUTHOR]

Inborn errors of immunity (IEIs) or primary immunodeficiency diseases, are disorders caused by genetic defects affecting immune function. Clinically, IEI presents mainly as recurrent or severe infections, immune dysregulation (autoimmunity or autoinflammatory disorders), and lymphoproliferation with or without dysmorphic features. Humoral IEIs are the largest subgroup of IEI, with a wide spectrum of quantitative and qualitative antibody defects. These disorders are normally diagnosed based on immunological evaluation; diagnostic vaccination is part of this evaluation. This review examines the importance and relevance of diagnostic vaccination in the diagnosis of humoral IEIs and different technologies which can be utilised in diagnosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

The amyloid hypothesis has so far been at the forefront of explaining the pathogenesis of Alzheimer's Disease (AD), a progressive neurodegenerative disorder that leads to cognitive decline and eventual death. Recent evidence, however, points to additional factors that contribute to the pathogenesis of this disease. These include the neurovascular hypothesis, the mitochondrial cascade hypothesis, the inflammatory hypothesis, the prion hypothesis, the mutational accumulation hypothesis, and the autoimmunity hypothesis. The purpose of this review was to briefly discuss the factors that are associated with autoimmunity in humans, including sex, the gut and lung microbiomes, age, genetics, and environmental factors. Subsequently, it was to examine the rise of autoimmune phenomena in AD, which can be instigated by a blood-brain barrier breakdown, pathogen infections, and dysfunction of the glymphatic system. Lastly, it was to discuss the various ways by which immune system dysregulation leads to AD, immunomodulating therapies, and future directions in the field of autoimmunity and neurodegeneration. A comprehensive account of the recent research done in the field was extracted from PubMed on 31 January 2022, with the keywords "Alzheimer's disease" and "autoantibodies" for the first search input, and "Alzheimer's disease" with "IgG" for the second. From the first search, 19 papers were selected, because they contained recent research on the autoantibodies found in the biofluids of patients with AD. From the second search, four papers were selected. The analysis of the literature has led to support the autoimmune hypothesis in AD. Autoantibodies were found in biofluids (serum/plasma, cerebrospinal fluid) of patients with AD with multiple methods, including ELISA, Mass Spectrometry, and microarray analysis. Through continuous research, the understanding of the synergistic effects of the various components that lead to AD will pave the way for better therapeutic methods and a deeper understanding of the disease. [ABSTRACT FROM AUTHOR]

Background: There is an increasing number of patients following hernia surgery with implanted mesh reporting symptoms that could indicate autoimmune or allergic reactions to mesh. 'Allergy' to metals, various drugs, and chemicals is well recognised. However, hypersensitivity, allergy or autoimmunity caused by surgical mesh has not been proven by a scientific method to date. The aim of this study was twofold: to describe the pathophysiology of autoimmunity and foreign body reaction and to undertake a systematic review of surgical mesh implanted at the time of hernia repair and the subsequent development of autoimmune disease. Methods: A systematic review using the PRISMA guidelines was undertaken. Pubmed (Medline), Google Scholar and Cochrane databases were searched for all English-written peer-reviewed articles published between 2000 and 2021. The search was performed using the keywords "hernia", "mesh", "autoimmunity", "ASIA", "immune response", "autoimmune response". Results: Seven papers were included in the final analysis—three systematic reviews, three cohort studies and one case report. Much of the current data regarding the association of hernia mesh and autoimmunity relies on retrospective cohort studies and/or case reports with limited availability of cofounding factor data linked to autoimmune disease such as smoking status or indeed a detailed medical history of patients. Three systematic reviews have discussed this topic, each with a slightly different approach and none of them has identified causality between the use of mesh and the subsequent development of autoimmune disease. Conclusion: There is little evidence that the use of polypropylene mesh can lead to autoimmunity. A large number of potential triggers of autoimmunity along with the genetic predisposition to autoimmune disease and the commonality of hernia, make a cause and effect difficult to unravel at present. Biomaterials cause foreign body reactions, but a chronic foreign body reaction does not indicate autoimmunity, a common misunderstanding in the literature. [ABSTRACT FROM AUTHOR]

COVID-19 infection not only profoundly impacts the detection of tuberculosis infection (Tbc) but also affects modality in tuberculosis patient immune response. It is important to determine immune response alterations in latent tuberculosis infection as well as in SARS-CoV-2-infected tuberculosis patients. Such changes may have underlying effects on the development and course of further tuberculosis. Here, we aimed to review the characteristics of immune response in TB patients or convalescent COVID-19 patients with latent TB infection (LTBI). Materials and Methods. We analyzed the features of immune response in tuberculosis and COVID-19 patients. For this, we analyzed publications released from December 2019 to March 2023; those which were published in accessible international databases ("Medline", "PubMed", "Scopus") and with keywords such as "COVID-19", "SARS-CoV-2", "tuberculosis", "pulmonary tuberculosis", "latent tuberculosis infection", "Treg", "follicular Treg", and "Treg subsets", we considered. Results. Through our analysis, we found that tuberculosis patients who had been infected with COVID-19 previously and elevated Th1 and Th2 cell levels. High levels of Th1 and Th2 cells may serve as a positive marker, characterizing activated immune response during TB infection. COVID-19 or post-COVID-19 subjects showed decreased Th17 levels, indicating a lack of tuberculosis development. Moreover, the typical course of tuberculosis is associated with an increase in Treg level, but COVID-19 contributes to a hyperinflammatory response. Conclusion. According to the data obtained, the course of tuberculosis proceeds in a dissimilar way due to the distinct immune response, elicited by SARS-CoV-2. Importantly, the development of active tuberculosis with a severe course is associated with a decline in Treg levels. Both pathogens lead to disturbed immune responses, increasing the risk of developing severe TB. The insights and findings of this paper may be used to improve the future management of individuals with latent and active tuberculosis. [ABSTRACT FROM AUTHOR]

The immune system plays a critical role in protecting the host against infection but is subject to numerous levels of control that are necessary to prevent pathological, tissue-damaging responses. Inappropriate inflammatory immune responses to self-antigens, innocuous commensal microorganisms, or environmental antigens can lead to chronic, debilitating, and degenerative diseases. Regulatory T cells have an essential, non-redundant, and dominant function in preventing pathological immune responses, as shown by the development of systemic fatal autoimmunity in humans and animals with a genetic deficiency in regulatory T cells. In addition to controlling immune responses, there is a growing understanding that regulatory T cells also contribute directly to tissue homeostasis by promoting tissue regeneration and repair. For these reasons, the prospect of enhancing regulatory T-cell numbers and/or function in patients represents an appealing therapeutic opportunity with potential applications in many diseases, including some where the pathological role of the immune system has only recently been recognized. Approaches to enhance regulatory T cells are now starting to be explored in clinical studies in humans. This review series brings together papers highlighting the Treg-enhancing approaches that are most advanced clinically and examples of therapeutic opportunities based on our growing understanding of regulatory T-cell functions., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Accumulating evidence shows that SARS‐CoV‐2 can potentially trigger autoimmune processes, which can be responsible for the long‐term consequences of COVID‐19. Therefore, this paper aims to review the autoantibodies reported in COVID‐19 convalescents. Six main groups were distinguished: (i) autoantibodies against components of the immune system, (ii) autoantibodies against components of the cardiovascular system, (iii) thyroid autoantibodies, (iv) autoantibodies specific for rheumatoid diseases, (v) antibodies against G‐protein coupled receptors, and (vi) other autoantibodies. The evidence reviewed here clearly highlights that SARS‐CoV‐2 infection may induce humoral autoimmune responses. However, the available studies share number of limitations, such as: (1) the sole presence of autoantibodies does not necessarily implicate the clinically‐relevant risks, (2) functional investigations were rarely performed and it is often unknown whether observed autoantibodies are pathogenic, (3) the control seroprevalence, in healthy, noninfected individuals was often not reported; thus it is sometimes unknown whether the detected autoantibodies are the result of SARS‐CoV‐2 infection or the accidental post‐COVID‐19 detection, (4) the presence of autoantibodies was rarely correlated with symptoms of the post‐COVID‐19 syndrome, (5) the size of the studied groups were often small, (6) the studies focused predominantly on adult populations, (7) age‐ and sex‐related differences in seroprevalence of autoantibodies were rarely explored, (8) genetic predispositions that may be involved in generation of autoantibodies during SARS‐CoV‐2 infections were not investigated, and (9) the autoimmune reactions following infection with SARS‐CoV‐2 variants that vary in the clinical course of infection remain unexplored. Further longitudinal studies are advocated to assess the link between identified autoantibodies and particular clinical outcomes in COVID‐19 convalescents. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis with nasal polyps (CRSwNP) has long been considered a benign, chronic inflammatory, and hyperplastic disease. Recent studies have shown that autoimmune-related mechanisms are involved in the pathology of nasal polyps. Activated plasma cells, eosinophils, basophils, innate type 2 lymphocytes, mast cells, and proinflammatory cytokine in polyp tissue indicate the mobilization of innate and adaptive immune pathways during polyp formation. The discovery of a series of autoantibodies further supports the autoimmune nature of nasal polyps. Local homeostasis dysregulation, infection, and chronic inflammation may trigger autoimmunity through several mechanisms, including autoantigens overproduction, microbial translocation, molecular mimicry, superantigens, activation or inhibition of receptors, bystander activation, dysregulation of Toll-Like Receptors (TLRs), epitope spreading, autoantigens complementarity. In this paper, we elaborated on the microbiome-mediated mechanism, abnormal host immunity, and genetic changes to update the role of autoimmunity in the pathogenesis of chronic rhinosinusitis with nasal polyps. [ABSTRACT FROM AUTHOR]

Currently, sarcoidosis remains one of the diseases with unknown etiology, which significantly complicates its diagnosis and treatment. Various causes of sarcoidosis have been studied for many years. Both organic and inorganic trigger factors, provoking the development of granulomatous inflammation are considered. However, the most promising and evidence-based hypothesis is the development of sarcoidosis as an autoimmune disease, provoked by various adjuvants in genetic predisposed individuals. This concept fits into the structure of the autoimmune/inflammatory syndrome, induced by adjuvants (ASIA) that was proposed in 2011 by Professor Shoenfeld Y. In this paper, the authors reveal the presence of major and minor ASIA criteria for sarcoidosis, propose a new concept of the course of sarcoidosis within the framework of ASIA, and point out the difficulties in creating a model of the disease and the selection of therapy. It is obvious that the data obtained not only bring us closer to understanding the nature of sarcoidosis, but also potentiate new studies confirming this hypothesis by obtaining a model of the disease. [ABSTRACT FROM AUTHOR]

Objective and design: The hallmark of type 2 inflammation is eosinophilia and/or high IgE serum levels, mostly in atopic dermatitis. Nevertheless, many dermatoses may present similar findings. Our aim is to explore the biological and clinical spectrum of cutaneous manifestations involving tissue and/or systemic eosinophilia, and distinct serum levels of IgE, where atopic dermatitis or other primary allergic eczema, not always is the definitive diagnosis. Materials/methods: A total of 37 scientific papers were enrolled in this narrative review. Results: A diagnostic approach for patients with elevated serum IgE level and a list of conditions not related to atopic dermatitis that runs through inborn errors of immunity, inflammatory disorders, lung disorders, malignancy, infections/infestations are displayed. Regarding to peripheral eosinophilia, differential diagnosis is also explored and clinical patterns of skin diseases associated with tissue eosinophilia are listed, to facilitate our diagnosis. Conclusions: We should maintain a high level of suspicion about other differential diagnosis involving eosinophilia and IgE dysregulation, especially in patients very young (when innate errors of the immunity may present) and in middle to elderly patients classified as having atopic dermatitis, due to the possibility of cutaneous hematological malignancies, paraneoplasia or autoimmune blistering diseases. [ABSTRACT FROM AUTHOR]

Cutaneous tuberculosis (CTB) is a very rare disease and accounts for only 1–2% of cases of extrapulmonary tuberculosis (EPTB). Due to the variety of its clinical manifestations, the uncharacteristic appearance of its lesions, resembling other dermatoses in the early stages, and the limited experience of clinicians due to the rarity of CTB, diagnosis is very difficult. Particularly noteworthy is the fact that most cases of EPTB, including skin tuberculosis (TB), can be a manifestation of systemic involvement. In this paper, we present a case of an immunocompromised patient who was diagnosed with CTB almost a year after the first dermatological lesions were located on the lower extremities. At the same time, due to respiratory symptoms, a diagnosis of pulmonary TB (PTB) was made, and radiological and microbiological confirmations were obtained. [ABSTRACT FROM AUTHOR]

Since vaccines are in fact manufactured chemical compounds such as drugs, the appearance of side effects following their use is not surprising. Similarly, as the main goal of vaccines is to stimulate the immune system bringing out the production of protective antibodies, autoimmune-related side effects as a consequence of increased immune activity do not seem irrational. Fortunately, the rate of such side effects is low; however, the importance of reporting adverse events following vaccinations, understanding the mechanisms behind their appearance, making early diagnosis, and appropriate treatment cannot be overemphasized. In fact, autoimmune-related side effects of vaccines, particularly those based on adjuvants, were reported long before the introduction of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). Nevertheless, ASIA gathered and united the side effects of vaccines under one title, a step which helped organize the research and call for better immune stimulators than adjuvants. New technologies and methods of making vaccines were clearly noticed during the pandemic of COVID-19 after the introduction of mRNA-based vaccines. In our current paper, we introduce the notion of side effects to vaccines, particularly those of autoimmune nature, the mechanisms of ASIA, and the main vaccines linked with the syndrome including the recent COVID-19 vaccines. The transition from side effects to ASIA is the main idea behind our work. [ABSTRACT FROM AUTHOR]

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Long Covid can affect anyone who has previously had acute COVID-19. The root causes of this syndrome are still unknown, and no effective therapeutics are available. This complex syndrome, with a wide array of symptoms, is still evolving. Given the dire situation, it is important to identify the causes of Long Covid and the changes occurring within the immune system of affected patients to figure out how to treat it. The immune system intersects with the persistent viral fragments and blood clots that are implicated in this syndrome; understanding how these complex systems interact may help in untangling the puzzling physiopathology of Long Covid and identifying mitigation measures to provide patients some relief. In this paper, we discuss evidence-based findings and formulate hypotheses on the mechanisms underlying Long Covid's physiopathology and propose potential therapeutic options. [ABSTRACT FROM AUTHOR]

There is growing evidence that inflammation secondary to immune activation is intimately connected to excitotoxicity. We now know that most peripheral tissues contain fully operational glutamate receptors. While most of the available research deals with excitotoxicity in central nervous system (CNS) tissues, this is no longer true. Even plant has been found to contain glutamate receptors. Most of the immune cells, including mask cells, contain glutamate receptors. The receptors are altered by inflammation, both chemokine and cytokines. A host of new diseases have been found that are caused by immunity to certain glutamate receptors, as we see with Rasmussen's encephalitis. In this paper, I try to explain this connection and possible ways to reduce or even stop the reaction. [ABSTRACT FROM AUTHOR]