Search

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]

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]

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]

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with hyperactive innate and adaptive immune systems that cause dermatological, cardiovascular, renal, and neuropsychiatric problems in patients. SLE's multifactorial nature and complex pathogenesis present significant challenges in its clinical classification. In addition, unpredictable treatment responses in patients emphasize the need for highly specific and sensitive SLE biomarkers that can assist in understanding the exact pathogenesis and, thereby, lead to the identification of novel therapeutic targets. Recent studies on microRNA (miRNA), a non-coding region involved in the regulation of gene expression, indicate its importance in the development of the immune system and thus in the pathogenesis of various autoimmune disorders such as SLE. miRNAs are fascinating biomarker prospects for SLE categorization and disease monitoring owing to their small size and high stability. In this paper, we have discussed the involvement of a wide range of miRNAs in the regulation of SLE inflammation and how their modulation can be a potential therapeutic approach. [ABSTRACT FROM AUTHOR]

The immune response plays a crucial role in preventing diseases, such as infections. There are two types of immune responses, specific and innate immunity, each of which consists of two components: cellular immunity and humoral immunity. Dysfunction in any immune system component increases the risk of developing certain diseases. Systemic lupus erythematosus (SLE), an autoimmune disease in the human body, develops an immune response against its own components. In these patients, due to underlying immune system disorders and receipt of immunosuppressive drugs, the susceptibility to infections is higher than in the general population and is the single largest cause of mortality in this group. COVID-19 infection, which first appeared in late 2019, has caused several concerns in patients with SLE. However, there is no strong proof of additional risk of developing COVID-19 in patients with SLE, and in some cases, studies have shown less severity of the disease in these individuals. This review paper discusses the immune disorders in SLE and COVID-19. [ABSTRACT FROM AUTHOR]

The International Union of Immunological Societies (IUIS) expert committee (EC) on Inborn Errors of Immunity (IEI) reports here the 2022 updated phenotypic classification, which accompanies and complements the most-recent genotypic classification. This phenotypic classification is aimed for clinicians at the bedside and focuses on clinical features and laboratory phenotypes of specific IEI. In this classification, 485 IEI underlying phenotypes as diverse as infection, malignancy, allergy, auto-immunity and auto-inflammation are described, including 55 novel monogenic defects and 1 autoimmune phenocopy. Therefore, all 485 diseases of the genetic classification are presented in this paper in the form of colored tables with essential clinical or immunological phenotype entries. [ABSTRACT FROM AUTHOR]

Ethyl pyruvate (EP) has potent influence on redox processes, cellular metabolism, and inflammation. It has been intensively studied in numerous animal models of systemic and organ-specific disorders whose pathogenesis involves a strong immune component. Here, basic chemical and biological properties of EP are discussed, with an emphasis on its redox and metabolic activity. Further, its influence on myeloid and T cells is considered, as well as on intracellular signaling beyond its effect on immune cells. Also, the effects of EP on animal models of chronic inflammatory and autoimmune disorders are presented. Finally, a possibility to apply EP as a treatment for such diseases in humans is discussed. Scientific papers cited in this review were identified using the PubMed search engine that relies on the MEDLINE database. The reference list covers the most important findings in the field in the past twenty years. [ABSTRACT FROM AUTHOR]

Autoimmune diseases—where the immune system mistakenly targets self-tissue—remain hindered by non-specific therapies. For example, even molecularly specific monoclonal antibodies fail to distinguish between healthy cells and self-reactive cells. An experimental therapeutic approach involves delivery of self-molecules targeted by autoimmunity, along with immune modulatory signals to produce regulatory T cells (TREG) that selectively stop attack of host tissue. Much has been done to increase the efficiency of signal delivery using biomaterials, including encapsulation in polymer microparticles (MPs) to allow for co-delivery and cargo protection. However, less research has compared particles encapsulating drugs that target different TREG inducing pathways. In this paper, we use poly (lactic-co-glycolide) (PLGA) to co-encapsulate type 1 diabetes (T1D)-relevant antigen and 3 distinct TREG-inducing molecules — rapamycin (Rapa), all-trans retinoic acid (atRA), and butyrate (Buty) — that target the mechanistic target of Rapa (mTOR), the retinoid pathway, and histone deacetylase (HDAC) inhibition, respectively. We show all formulations are effectively taken up by antigen presenting cells (APCs) and that antigen-containing formulations are able to induce proliferation in antigen-specific T cells. Further, atRA and Rapa MP formulations co-loaded with antigen decrease APC activation levels, induce TREG differentiation, and reduce inflammatory cytokines in pancreatic-reactive T cells. [ABSTRACT FROM AUTHOR]

Introduction: Immunoglobulin A vasculitis (IgAV) is the most common form of childhood systemic vasculitis. It is mostly self-limiting and characterized by skin, joint, gastrointestinal tract, and kidney involvement. Microribonucleic acids (miRNAs) are 18–25 base-long non-coding RNA group acting on gene expression. They have been shown to be effective on the immune system studies to date. Method: In our study, 24 IgAV children with skin and joint involvement and 24 healthy children were included. Five different miRNAs (miR-33, miR-34, miR-122, miR-204, and miR451) known to be expressed in plasma and related with autoimmunity pathogenesis were evaluated. miRNAs were compared between the active period of the disease, the post-treatment period, and the healthy group using the real-time PCR method. Results: Expression levels of miRNA-33 and miRNA-34 increased significantly in active period of the patients compare with inactive period and control groups. The expression levels of miRNA-122 and miRNA-204 decreased significantly in active period of the patients compare with other two groups. There was no significant difference in miRNA-451 levels. Conclusions: With the experience we gained from our recent studies, we think that miRNA-204 may be a significant biomarker in autoimmune diseases. Our study is the first study between IgAV and miRNAs in children. More studies are needed to reveal this relationship. Key Points • This is the first paper to show the relationship between miRNAs and childhood IgAV. • It will provide a new perspective to evaluate the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Skin lesions have been reported in about 10–12% of hairy cell leukemia (HCL) patients. Most are etiologically related to autoimmune or infectious processes, although secondary cutaneous neoplasms and drug-induced lesions are also reported. However, leukemia cutis with the direct infiltration of the skin by leukemic cells is extremely rare in HCL patients. This paper reviews the epidemiology, pathogenesis, clinical symptoms, diagnosis, and approach to treating skin lesions in HCL. A literature review of the MEDLINE database for articles in English concerning hairy cell leukemia, skin lesions, leukemia cutis, adverse events, infectious, cutaneous, drug reactions, neutrophilic dermatoses, secondary neoplasms, and vasculitis was conducted via PubMed. Publications from January 1980 to September 2020 were scrutinized. Additional relevant publications were obtained by reviewing the references from the chosen articles. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is frequently accompanied by diverse neuropsychiatric manifestations. An increased frequency of olfactory deficits has been recently reported as another marker of CNS involvement in SLE patients. Similarly, we observed that spontaneous development of lupus-like disease in MRL/lpr mice is accompanied by altered olfaction-related behaviors. However, it remained unclear whether the behavioral deficits are due to systemic autoimmunity, or the distinct genetic make-up. To address this question, we presently examine whether prolonged treatment with the immunosuppressive drug cyclophosphamide (CY) restores odor-guided behaviors in MRL/lpr mice. Over 12 weekends, MRL/lpr and control MRL +/+ males were given ad lib access to a sweetened CY solution or a vehicle. Their responsiveness to different scents was assessed at ages corresponding to mild, modest, and severe disease. Odor-guided exploratory behavior was further examined in the novel object test at 21 weeks of age, shortly before terminal assessment of immunopathology. In comparison to control groups, MRL/lpr mice exposed to CY exhibited normal spleen size and antibody levels, as well as increased responsiveness to an attractant and a novel object. However, CY treatment also exacerbated their aberrant response to a repellent, suggesting a dual mode of action on brain olfactory systems. The present results reveal that generalized immunosuppression modulates odor-guided behaviors in lupus-prone animals. Although key pathogenic mechanisms are not clear, the findings strengthen the construct validity of the MRL model by supporting the hypothesis that onset of systemic autoimmunity alters the activity of olfactory circuits. [ABSTRACT FROM AUTHOR]

Steroid-responsive encephalopathy is a general term for diseases that are characterized by diffuse brain injury and respond well to corticosteroids or immunosuppressive agents, including Hashimoto's encephalopathy (HE), limbic encephalitis (LE), systemic lupus erythematosus encephalopathy (SLEE), antineutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis encephalopathy (AASV), viral encephalitis (VE), and primary central nervous system lymphoma (PCNSL). Epilepsy and status epilepticus are the main manifestations of steroid-responsive encephalopathy. The spectrum of "autoimmune epilepsy" diseases, which has been approved by the epilepsy diagnostic recommendations of the International Antiepileptic League, is characterized by a high prevalence of epilepsy in central nervous system (CNS) autoimmune diseases and a variety of neuron-specific autoantibodies. Steroid-responsive encephalopathy with different causes may have different pathogeneses and has been suggested to be associated with some internal commonality producing seizure as the main symptom. Determining the regularity of seizures caused by steroid-responsive encephalopathy and implementing appropriate measures will help us improve the prognosis of patients. This paper summarizes the epidemiology, seizure onset, seizure type, and other characteristics of seizures in steroid-responsive encephalopathy (including HE, LE, SLEE, ANCA-associated systemic vasculitis encephalopathy, VE, and PCNSL) and then discusses the use of antiepileptic drugs to treat steroid-responsive encephalopathy. [ABSTRACT FROM AUTHOR]

Aging is a highly complex process that results in the dysregulation of all systems in the human organism. The most important changes in the immune system, which are collectively known as immunosenescence, include lower levels of immunoresponse to infections, increased levels of proinflammatory mediators, and weakened control over self-reactive clones. In elderly people, immunoscenescence is usually observed along with low-grade, aseptic inflammation (inflammaging) which is considered to be associated with a higher incidence of chronic, noninfectious, age-related diseases. This paper discusses the main changes in the innate and adaptive immunity in aging and their impact on the induction of autoimmune processes and provides data on the frequency of autoantibody detection in elderly people and the clinical patterns of certain autoimmune diseases that manifest first at this age. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: This paper presents the relationship between islet autoantibodies, precursors of type 1 diabetes, and the development of persistent asthma, allergic rhinitis and atopic eczema. Methods: A total of 2159 newborns who had a first-degree relative with type 1 diabetes and selected HLA genotypes were followed until the youngest participant reached 10 years of age. Islet cell antibodies (ICA) were detected using indirect immunofluorescence. Autoantibodies to insulin (IAA), GAD (GADA), the tyrosine phosphatase-related insulinoma-associated 2 molecule (IA-2A) and zinc transporter 8 (ZnT8A) were quantified with the use of specific radiobinding assays. As an ancillary study, the incidence of asthma, allergic rhinitis and eczema was assessed in 1106 of these children using the International Study of Asthma and Allergies in Childhood (ISAAC) core questionnaire when the children were 9–11 years old. HRs with 95% CIs were calculated to depict the incidence of these diseases following seroconversion to autoantibody positivity. Results: The cumulative incidence of atopic eczema, allergic rhinitis and persistent asthma were 22%, 9% and 7.5%, respectively, by 9–11 years of age. The occurrence of diabetes-related autoantibodies showed a protective association with subsequently reported incidence of asthma and eczema. The incidence of rhinitis was not significantly related to the occurrence of IAA or GADA (statistical power was limited), but demonstrated the same inverse relationship as did the other diseases with ICA or when multiple autoantibodies first appeared together. Conclusions/interpretation: The findings add evidence to the relationships between these atopic diseases and diabetes-related autoimmunity and also suggest that, for eczema, the interaction depends upon which autoantibody appeared first. Trial registration: ClinicalTrials.gov NCT00179777 [ABSTRACT FROM AUTHOR]

In an instant classic paper (Lazebnik, in Cancer Cell 2(3); : 179-182) biologist Yuri Lazebnik deplores the poor effectiveness of the approach adopted by biologists to understand and 'fix' biological systems. Lazebnik suggests that to remedy this state of things biologist should take inspiration from the approach used by engineers to design, understand, and troubleshoot technological systems. In the present paper I substantiate Lazebnik's analysis by concretely showing how to apply the engineering approach to biological problems. I use an actual example of electronic circuit troubleshooting to ground the thesis that, in engineering, the crucial phases of any non-trivial troubleshooting process are aimed at generating a mechanistic explanation of the functioning of the system, which makes extensive recourse to problem-driven qualitative reasoning possibly based on cognitive artifacts applied to systems that are known to have been designed for function. To show how to translate these findings into biological practice I consider a concrete example of biological model building and 'troubleshooting', aimed at the identification of a 'fix' for the human immune system in presence of progressing cancer, autoimmune disease, and transplant rejection. The result is a novel immune system model-the danger model with regulatory cells- and new, original hypotheses concerning the development, prophylaxis, and therapy of these unwanted biological processes. Based on the manifest efficacy of the proposed approach, I suggest a refocusing of the activity of theoretical biologists along the engineering-inspired lines illustrated in the paper. [ABSTRACT FROM AUTHOR]

Hair loss in the autoimmune disease, alopecia areata (AA), is characterized by the appearance of circularly spreading alopecic lesions in seemingly healthy skin. The distinct spatial patterns of AA lesions form because the immune system attacks hair follicle cells that are in the process of producing hair shaft, catapults the mini-organs that produce hair from a state of growth (anagen) into an apoptosis-driven regression state (catagen), and causes major hair follicle dystrophy along with rapid hair shaft shedding. In this paper, we develop a model of partial differential equations (PDEs) to describe the spatio-temporal dynamics of immune system components that clinical and experimental studies show are primarily involved in the disease development. Global linear stability analysis reveals there is a most unstable mode giving rise to a pattern. The most unstable mode indicates a spatial scale consistent with results of the humanized AA mouse model of Gilhar et al. (Autoimmun Rev 15(7):726–735, 2016) for experimentally induced AA lesions. Numerical simulations of the PDE system confirm our analytic findings and illustrate the formation of a pattern that is characteristic of the spatio-temporal AA dynamics. We apply marginal linear stability analysis to examine and predict the pattern propagation. [ABSTRACT FROM AUTHOR]

Standardisation of immuno-assays for autoantibodies is a major challenge. Although multiple organisations participate in the generation of internationally accepted standards, adequate standardisation of assays has not yet been achieved. Harmonisation may offer an alternative approach to better align requesting, testing, reporting and interpretation of autoimmune diagnostics. The European Autoimmunity Standardisation Initiative (EASI) was founded to facilitate both standardisation as well as harmonisation of autoantibody tests, but over the years the focus has drifted away from standardisation in favour of harmonisation. In the current paper the options for harmonisation are highlighted. [ABSTRACT FROM AUTHOR]

The presence of naturally occurring cytokine-specific autoantibodies (c-aAb) in humans is well established, as well as associations to selected pathologies. However, the overall influence of c-aAb on immunocompetence remains largely unknown. In this paper, we performed a large-scale investigation of c-aAb association with infection risk. A cohort of healthy Danish blood donors was screened for c-aAb against IL-1α, IL-6, IL-10, IFNα, and GM-CSF using a Luminex-based multiplex assay, and results were linked to data from the Danish National Prescription Registry. The filing of an antimicrobial prescription following c-aAb measurement was used as a proxy for impaired immunocompetence. We found that c-aAb against pro-inflammatory cytokines IFNα and GM-CSF tended to associate with increased risk of prescription filings in women, whereas antibodies against anti-inflammatory IL-10 were associated with a lower predicted risk of antimicrobial prescriptions, as well as higher self-perceived health scores. We also observed an association of cumulative c-aAb presence with prescription risk. Our data show that cytokine autoantibodies in healthy individuals associate with various proxies for immunomodulation, with the exact association dependent on the pattern of pro- or anti-inflammatory cytokines targeted. This suggests that c-aAb may express cytokine-modulatory properties in healthy individuals and may be critical to further investigate as biomarkers of immunodeficiency. [ABSTRACT FROM AUTHOR]

Purpose: Primary ovarian insufficiency (POI) represents ovarian dysfunction related to very early aging of the ovaries. While the cause of POI in a majority of clinical cases remains undefined, autoimmunity is responsible for approximately 4–30% of POI cases. In the present paper, we aim to provide a critical appraisal and update review on the role of autoimmunity in POI patients. Methods: A literature review was conducted for all relevant articles reporting on POI and autoimmunity. PubMed/MEDLINE and the Cochrane library were searched for the best available evidence on this topic. Results: Patients with POI and coexisting autoimmunity are indistinguishable from those with negative autoimmune screen with regard to age of onset, prevalence of primary amenorrhea, or their endocrine profiles. A specific noninvasive reliable diagnostic test for the diagnosis of an autoimmune etiology is lacking; therefore, patients should be screened for the most common autoantibodies, i.e., steroid cell antibodies, anti-ovarian antibodies, and anti-thyroid antibodies. Moreover, treatment strategies to POI infertility are lacking and controversial. Conclusions: Nowadays, guidelines for the treatment of autoimmune POI are not available. Moreover, since diagnostic and treatment strategies to POI infertility are still lacking and controversial, further large clinical studies are needed to investigate the true impact of autoimmunity on POI and to identify the selected groups of patients who are most likely to benefit from immunossuprresive treatment. [ABSTRACT FROM AUTHOR]

The purpose of this study is to describe both clinical and immunological features in large cohort of adult patients with IgG subclass deficiency, and response to immunoglobulin therapy. This is a retrospective study of data obtained from electronic medical records and paper charts of 78 patients with IgG subclass deficiency seen and followed at our immunology clinics from 2010 to 2016. Both isolated selective IgG subclass deficiency as well as combined (two) subclass deficiencies were observed. IgG3 subclass deficiency, isolated and in combination with other IgG subclass deficiency, is the most frequent of IgG subclass deficiency. A majority of patients presented with upper and lower respiratory tract infections, especially chronic sinusitis. Both allergic and autoimmune manifestations are common; however, there is no subclass preference. The proportions and absolute numbers of CD3+ T cells, CD4+ T and CD8+ T cells, CD19+ B cells, and CD3−CD16+CD56+ NK cells were normal in the majority of patients in all IgG subclass deficiencies. Total serum IgG levels did not correlate with IgG subclass levels across all IgG subclass deficiencies. Anti-pneumococcal polysaccharide antibody responses were impaired in 56% of patients. IgG3 subclass deficiency is the most common IgG subclass deficiency, and anti-polysaccharide antibody responses are distributed among IgG subclasses with modest preference in IgG2 subclass. The majority of patients treated with immunoglobulin responded by reduction in frequency of infections and requirement of antibiotics. [ABSTRACT FROM AUTHOR]

At the outbreak of the Covid-19 pandemic, several countries declared “states of exception,” that is, authorized legal devices that, in the face of circumstances deemed catastrophic, permit the implementation of extraordinary measures and the temporary suspension of some rights in order to restore the previous state of affairs as soon as possible. This paper offers a comparative textual analysis of the different states of exception declared in the USA, France, and Spain. I argue that these texts constitute a privileged site to explore how prevalent global political logics and mainstream discourses on illness are interwoven. Regarding the global political logics in play, I hold that these declarations constitute an instantiation of democracy’s autoimmune character; it attacks itself in order to protect itself. Regarding mainstream discourses on illness, I explore how illness is regarded as a threat to one’s self (by something seemingly other) and the notion that therapy must consist of securing the self’s triumph over anything seemingly other. This twofold analysis reveals that an aporetic dialectic between self and other—as regards politics and illness—operates in these declarations, most likely because it is, in fact, one and the same dialectic, upon which Western epistemology rests. Furthermore, I suggest that these texts reflect and promote these dominant logics, contributing to shape human relationships around the globe in a certain dangerous way. [ABSTRACT FROM AUTHOR]

B cells and T cells collaborate in multiple sclerosis (MS) pathogenesis. IgH[MOG] mice possess a B cell repertoire skewed to recognize myelin oligodendrocyte glycoprotein (MOG). Here, we show that upon immunization with the T cell-obligate autoantigen, MOG[35-55], IgH[MOG] mice develop rapid and exacerbated experimental autoimmune encephalomyelitis (EAE) relative to wildtype (WT) counterparts, characterized by aggregation of T and B cells in the IgH[MOG] meninges and by CD4+ T helper 17 (Th17) cells in the CNS. Production of the Th17 maintenance factor IL-23 is observed from IgH[MOG] CNS-infiltrating and meningeal B cells, and in vivo blockade of IL-23p19 attenuates disease severity in IgH[MOG] mice. In the CNS parenchyma and dura mater of IgH[MOG] mice, we observe an increased frequency of CD4+PD-1+CXCR5- T cells that share numerous characteristics with the recently described T peripheral helper (Tph) cell subset. Further, CNS-infiltrating B and Tph cells from IgH[MOG] mice show increased reactive oxygen species (ROS) production. Meningeal inflammation, Tph-like cell accumulation in the CNS and B/Tph cell production of ROS were all reduced upon p19 blockade. Altogether, MOG-specific B cells promote autoimmune inflammation of the CNS parenchyma and meninges in an IL-23-dependent manner. B cells are crucial in multiple sclerosis (MS) pathology but the mechanisms are incompletely understood. In a mouse model of MS, the authors show that B cells make IL-23, and that IL-23 invokes meningeal inflammation and CNS presence of T peripheral helper cells. [ABSTRACT FROM AUTHOR]

Previously, we described an animal model for interstitial cystitis (IC), experimental autoimmune cystitis (EAC) [Luber-Narod et al. Urol Res 24:367]. Further characterization of animals with EAC indicates that peak and mean urinary frequency are elevated compared with sham-injected controls and that the disease progresses with at least two cycles of exacerbations and remissions. We had shown evidence suggesting EAC to be autoimmune in nature. In this paper, we identify serum autoantibodies from 9/10 EAC animals which bind to a protein specific to rat bladder with a relative molecular weight of 12-kDa. Such autoantibodies are absent in 12/13 normal and sham-injected animals as well as animals which fail to develop EAC despite disease induction. These findings suggest that EAC is a reproducible model of cyclical increases of urinary frequency, and that a 12-kDa antigen is the target of autoantibodies which correlate with those elevations. Identification of this target antigen may explain the pathogenesis of increased urinary frequency in these animals and potentially in IC as well. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a widespread condition that appears to be increasing in prevalence and severity worldwide, yet the underlying mechanisms are not well understood. Recent research has identified various similarities between AD and autoimmune conditions, as well as indicating that there may be an association between AD and autoimmunity. This systematic review evaluates the association between AD and autoimmunity, as well as between severity of disease in AD and autoimmunity, with an emphasis on the associations with autoantibodies. MEDLINE (1946 to December 2017) and Embase (1974 to December 2017) databases were searched. Further relevant articles were retrieved from reference lists. Only studies measuring direct indicators of autoimmunity, in humans, were included. Qualitative analysis was carried out for all studies. In addition, quantitative analysis was used to evaluate prevalence of IgE autoantibodies and anti-nuclear antibodies (ANAs) in AD patients and control subjects. The Mantel-Haenszel method was used with a random-effects model. 28 studies assessed the occurrence of autoantibodies in AD patients and 16 studies were used to evaluate association between disease severity and autoantibodies. Pooled analysis from 14 studies, involving 986 AD patients and 441 control subjects, showed that IgE autoantibodies were significantly more prevalent in patients with AD (P < 0.00001) than control subjects. Similar analysis was carried out for ANAs, with eight studies that involved 1045 AD patients and 1273 control subjects. ANAs were significantly more prevalent in patients with AD (P = 0.003). This quantitative analysis supported an association between AD and IgE autoantibodies, as well as between AD and ANAs. There was insufficient data to make similar conclusions for other indicators of autoimmunity. The weight of evidence also suggests an association between IgE autoantibodies and disease severity. There was insufficient evidence to make this link for other indicators of autoimmunity. [ABSTRACT FROM AUTHOR]

Purpose of Review: The association between extrahepatic malignancy and primary biliary cholangitis (PBC) has been studied only partially. The goal of this paper is to update this topic, reviewing the most recent literature.Recent Findings: Studies comparing the incidence of cancer with the general population and meta-analysis studies failed to find a specific association between extrahepatic malignancy (including breast cancer, gastrointestinal cancers, reproductive tumors, and myeloproliferative diseases) and PBC. Moreover, it has been found that the development of cancer does not influence the natural history of the disease. The risk factors associated with cancer development are advanced histological stage and extrahepatic autoimmunity.Summary: Cancer screening programs for PBC patients are not needed other than those already present for the general population. However, more high-quality case-control studies on the stratification of risk for extrahepatic cancers in PBC are warranted in the future. [ABSTRACT FROM AUTHOR]

Since the discovery of HLA 60 years ago, it has contributed to the understanding of the immune system as well as of the pathogenesis of several diseases. Aside from its essential role in determining donor-recipient immune compatibility in organ transplantation, HLA genotyping is meanwhile performed routinely as part of the diagnostic work-up of certain autoimmune diseases. Considering the ability of HLA to influence thymic selection as well as peripheral anergy of T cells, its role in the pathogenesis of autoimmunity is understandable. The aim of this paper is to provide a brief overview of the role and current clinical relevance of HLA-B27 in spondyloarthritis and HLA-B51 in Behçet's disease as well as HLA-DQ2/DQ8 in celiac disease and HLA-DRB1 in rheumatoid arthritis and to discuss possible future implications. [ABSTRACT FROM AUTHOR]

Background and purpose: Myasthenia gravis (MG) is an autoimmune disease with muscular weakness as the only symptom, and often with immunosuppressive treatment. All these aspects could have relevance for the risk of infections as well as their prophylactic and curative treatment.Methods: This is a review article, where Web of Science has been searched for relevant key words and key word combinations. Full papers were selected first by title and then by abstract.Results and conclusions: MG can be triggered and worsened by infections. No virus or other pathogen has been proven to have a specific link to MG. Treatment with immunosuppressive drugs and thymectomy implies a slightly increased risk for infections. Infections should be actively treated, but a few antibiotics are avoided due to potential interference with neuromuscular transmission. Hospitalization and intensive care may be necessary during infections because of MG deterioration and risk of insufficient respiration. Vaccinations are generally recommended in MG, but live microorganisms should be avoided if possible in immunosuppressed patients. [ABSTRACT FROM AUTHOR]

Celiac disease has advanced from a medical rarity to a highly prevalent disorder. Patients with the disease show varying degrees of chronic inflammation within the small intestine due to an aberrant immune response to the digestion of gliadin found in wheat. As a result, cytokines and antibodies are produced in celiac patients that can be used as specific biomarkers for developing diagnostic tests. This review paper describes celiac disease in terms of its etiological cause, pathological effects, current diagnostic tests based on mucosal biopsy, and the genetic basis for the disease. In addition, it discusses the use of gliadin-induced cytokines, antibodies and autoantibodies as a diagnostic tool for celiac disease. Despite good initial results in terms of sensitivity and specificity, when these immunological tests were used on a large scale, even in combination with genetic testing, the results showed lower predictive value. This review addresses that issue and ends with an outlook on future work required to develop diagnostic tests with greater accuracy in predicting celiac disease in the general public, thus avoiding the need for endoscopy and mucosal biopsy. [ABSTRACT FROM AUTHOR]

De novo synthesis of the pyrimidine, cytidine triphosphate (CTP), is crucial for DNA/RNA metabolism and depends on the CTP synthetases, CTPS1 and −2. Partial CTPS1 deficiency in humans has previously been shown to lead to immunodeficiency, with impaired expansion of T and B cells. Here, we examine the effects of conditional and inducible inactivation of Ctps1 and/or Ctps2 on mouse embryonic development and immunity. We report that deletion of Ctps1, but not Ctps2, is embryonic-lethal. Tissue and cells with high proliferation and renewal rates, such as intestinal epithelium, erythroid and thymic lineages, activated B and T lymphocytes, and memory T cells strongly rely on CTPS1 for their maintenance and growth. However, both CTPS1 and CTPS2 are required for T cell proliferation following TCR stimulation. Deletion of Ctps1 in T cells or treatment with a CTPS1 inhibitor rescued Foxp3-deficient mice from fatal systemic autoimmunity and reduced the severity of experimental autoimmune encephalomyelitis. These findings support that CTPS1 may represent a target for immune suppression. Cytidine nucleotide triphosphate (CTP) is a key precursor involved in the metabolism of DNA, RNA and phospholipids. In this study, the authors examine the physiological consequences of CTP synthase (Ctps) 1 and 2 deletion in vivo and demonstrate that Ctps1 protects mice from fatal autoimmunity. [ABSTRACT FROM AUTHOR]

Mature dendritic cells (DCs) are crucial for the induction of adaptive immune responses and perturbed DC homeostasis can result in autoimmune disease. Either uncontrolled expansion or enhanced survival of DCs can result in a variety of autoimmune diseases in mouse models. In addition, increased maturation signals, through overexpression of surface Toll-like receptors (TLRs) or stimulation by type I interferon (IFN), has been associated with systemic autoimmunity. Whereas recent studies have focused on identifying factors required for initiating the maturation process, the possibility that resting DCs also express molecules that 'hold' them in an immature state has generally not been considered. Here we show that nuclear factor-?B1 (NF-?B1) is crucial for maintaining the resting state of DCs. Self-antigen-pulsed unstimulated DCs that do not express NF-?B1 were able to activate CD8+ T lymphocytes and induce autoimmunity. We further show that NF-?B1 negatively regulates the spontaneous production of tumor necrosis factor-? (TNF-?), which is associated with increased granzyme B expression in cytotoxic T lymphocytes (CTLs). These findings provide a new perspective on functional DC maturation and a potential mechanism that may account for pathologic T cell activation. [ABSTRACT FROM AUTHOR]

In ‘Force of law’ Derrida appears to suggest that emancipatory ideals and human rights have a continuing relevance. This may seem a surprising proposition from a theorist often interpreted as critical of humanist and Enlightenment principles. This paper argues, however, that Derrida does not reject, outright, humanist, Enlightenment and emancipatory strategies but instead deconstructs these in order to propose alternate ‘ethical’ and ‘political’ possibilities. Focusing on ‘The ends of man’, ‘Force of law’ and ‘Autoimmunity’ this paper argues that Derrida does not advocate an anti-humanism but instead gestures toward an alternate unconditional hospitality, responsibility, friendship, justice and democracy-to-come, displacing the anthropomorphism of humanism and advocating instead an openness to a heterogeneous otherness. [ABSTRACT FROM AUTHOR]

In this paper, the authors reported the symptoms and immunological findings of patients who were infected from severe acute respiratory syndrome coronovirus-2 (SARS-CoV-2). On the other hand, SARS-CoV-2 may trigger autoimmune responses and the development of de-novo manifestations of ARDs, as in our patient [[3]]. Recently, we reported a patient who contracted SARS-CoV-2 infection and developed an erosive seronegative arthritis six months after infection [[2]]. [Extracted from the article]

Anti-Ro52/tripartite motif-containing 21 (TRIM21) is a ubiquitous antibody found in a number of systemic autoimmune conditions including Sjögren's syndrome, systemic lupus erythematosus and systemic sclerosis, appearing in about half of these patients. Once coupled with its closely related antibody, anti-Ro60 as the anti-SSA antibody, anti-Ro52 is emerging as a unique antibody with direct pathogenic disease involvement and distinct clinical properties. As a result, recent attention has turned to this antibody and its clinical associations and utility. There is a suggestion of anti-Ro52 being associated with more clinical and laboratory markers of disease; however, marked disagreements occur about its association with various clinical entities such as interstitial lung disease and Raynaud's phenomena. Nevertheless, with a relative paucity of studies about these across the systemic autoimmunity paradigm, limited confidence can be invested in these conclusions. Although the antibody holds great potential as a biomarker, further studies examining its clinical utility are needed. This paper will review the mechanisms of Ro52 as an autoantigen and the clinical associations of anti-Ro52 in human autoimmunity. [ABSTRACT FROM AUTHOR]

In this paper, dynamical systems theory and bifurcation theory are applied to investigate the rich dynamical behaviours observed in three simple disease models. The 2- and 3-dimensional models we investigate have arisen in previous investigations of epidemiology, in-host disease, and autoimmunity. These closely related models display interesting dynamical behaviors including bistability, recurrence, and regular oscillations, each of which has possible clinical or public health implications. In this contribution we elucidate the key role of backward bifurcations in the parameter regimes leading to the behaviors of interest. We demonstrate that backward bifurcations with varied positions of turning points facilitate the appearance of Hopf bifurcations, and the varied dynamical behaviors are then determined by the properties of the Hopf bifurcation(s), including their location and direction. A Maple program developed earlier is implemented to determine the stability of limit cycles bifurcating from the Hopf bifurcation. Numerical simulations are presented to illustrate phenomena of interest such as bistability, recurrence and oscillation. We also discuss the physical motivations for the models and the clinical implications of the resulting dynamics. [ABSTRACT FROM AUTHOR]

The role of genetic and epigenetic factors in the development of rheumatic diseases has been an interesting field of research over the past decades all around the world. Research on the role of microRNAs (miRNAs) in rheumatoid arthritis (RA) has been active and ongoing, and investigations have attempted to use miRNAs as biomarkers in disease diagnosis, prognosis, and treatment. This review focuses on experimental researches in the field of miRNAs and RA to present the data available up to this date and includes researches searched by keywords 'microRNA' and 'rheumatoid arthritis' in PubMed from 2008 to January 2015. All references were also searched for related papers. miRNAs are shown to act as proinflammatory or anti-inflammatory agents in diverse cell types, and their role seems to be regulatory in most instances. Researchers have evaluated miRNAs in patients compared to controls or have investigated their role by overexpressing or silencing them. Multiple targets have been identified in vivo, in vitro, or in silico, and the researches still continue to show their efficacy in clinical settings. [ABSTRACT FROM AUTHOR]

Cancers and autoimmune diseases commonly co-exist and immune checkpoint inhibitor therapy (ICI) exacerbates autoimmune pathologies. We recently described a lipidic peptide, designated IK14004, that promotes expansion of immunosuppressive T regulatory (Treg) cells and uncouples interleukin-2 from interferon-gamma production while activating CD8+ T cells. Herein, we report IK14004-mediated inhibition of Lewis lung cancer (LLC) growth and re-invigoration of splenocyte-derived exhausted CD4+ T cells. In human immune cells from healthy donors, IK14004 modulates expression of the T cell receptor α/β subunits, induces Type I IFN expression, stimulates natural killer (NK) cells to express NKG2D/NKp44 receptors and enhances K562 cytotoxicity. In both T and NK cells, IK14004 alters the IL-12 receptor β1/β2 chain ratio to favour IL-12p70 binding. Taken together, this novel peptide offers an opportunity to gain further insight into the complexity of ICI immunotherapy so that autoimmune responses may be minimised without promoting tumour evasion from the immune system. [ABSTRACT FROM AUTHOR]

Inhibition of Janus kinase (JAK) family enzymes is a popular strategy for treating inflammatory and autoimmune skin diseases. In the clinic, small molecule JAK inhibitors show distinct efficacy and safety profiles, likely reflecting variable selectivity for JAK subtypes. Absolute JAK subtype selectivity has not yet been achieved. Here, we rationally design small interfering RNAs (siRNAs) that offer sequence-specific gene silencing of JAK1, narrowing the spectrum of action on JAK-dependent cytokine signaling to maintain efficacy and improve safety. Our fully chemically modified siRNA supports efficient silencing of JAK1 expression in human skin explant and modulation of JAK1-dependent inflammatory signaling. A single injection into mouse skin enables five weeks of duration of effect. In a mouse model of vitiligo, local administration of the JAK1 siRNA significantly reduces skin infiltration of autoreactive CD8+ T cells and prevents epidermal depigmentation. This work establishes a path toward siRNA treatments as a new class of therapeutic modality for inflammatory and autoimmune skin diseases. Therapeutic modulation of Janus kinase family enzymes is an established approach for inflammatory and autoimmune skin diseases. Here the authors rationally design small interfering RNAs to enable single Janus kinase targeting and test this new therapeutic approach in a skin disease model for maintaining efficacy and improving selectivity. [ABSTRACT FROM AUTHOR]

Regulatory T cells (Treg) are CD4+ T cells with immune-suppressive function, which is defined by Foxp3 expression. However, the molecular determinants defining the suppressive population of T cells have yet to be discovered. Here we report that the cell surface protein Lrig1 is enriched in suppressive T cells and controls their suppressive behaviors. Within CD4+ T cells, Treg cells express the highest levels of Lrig1, and the expression level is further increasing with activation. The Lrig1+ subpopulation from T helper (Th) 17 cells showed higher suppressive activity than the Lrig1- subpopulation. Lrig1-deficiency impairs the suppressive function of Treg cells, while Lrig1-deficient naïve T cells normally differentiate into other T cell subsets. Adoptive transfer of CD4+Lrig1+ T cells alleviates autoimmune symptoms in colitis and lupus nephritis mouse models. A monoclonal anti-Lrig1 antibody significantly improves the symptoms of experimental autoimmune encephalomyelitis. In conclusion, Lrig1 is an important regulator of suppressive T cell function and an exploitable target for treating autoimmune conditions. Regulatory T cells, and to certain extent other T cell subsets, limit the immune response to avoid harmful inflammation and tissue damage. Here authors identify a surface molecule, Lrig1, that is directly responsible for the suppressive function in regulatory T cells and in Il-17-producing helper T cells. [ABSTRACT FROM AUTHOR]

Introduction: Pyoderma gangrenosum (PG) is a rare ulcerative skin disease characterized by a wide variety in its clinical presentation and outcome. The etiology is unknown and the pathogenesis is poorly understood, but autoimmune mechanisms have been suggested. Gynecological reports about PG are particularly scarce. As gynecologists rarely encounter this disorder, the correct diagnosis can easily be missed. Patients and Methods: This paper presents the first case to our knowledge of an idiopathic PG of the vaginal vault as a late complication after vaginal hysterectomy. Conclusion: We demonstrate how PG, a rare disorder, might be misdiagnosed and how only the correct diagnosis and treatment involving systemic glucocorticoids and wound care can spare the patients from long-term morbidity. [ABSTRACT FROM AUTHOR]

In recent years, there has been an increased recognition that vitamin D is not only a risk factor for poor musculoskeletal health but also a possible important contributor in the development of different autoimmune diseases. This has been linked to multiple immunosuppressive properties of vitamin D. Vitamin D has got pleiotropic effects and this reflects the wide spread presence of vitamin D receptors (VDRs) throughout the body. Currently, there is much ongoing research with regard to its emerging role in immunopathology. VDR has not only been found in tissues involved in calcium homeostasis but also in a variety of cell lines involved primarily in immune regulation, e.g., mononuclear cells, dendritic cells, antigen-presenting cells, and activated B lymphocytes and CD4+ T cells. There have been several reports linking the presence of low vitamin D to various autoimmune diseases. However, for autoimmune/inflammatory disease outcomes, firm conclusions regarding cause and effect cannot be based on epidemiological association studies, and prospective, long-term, well-designed studies, including large intervention trials, are needed across all life stages. In this paper, we will describe the evidence base for this potential role of vitamin D in different aspects of autoimmune diseases. Because of the enormous breadth of this emerging field, our aim in this review is not to provide an exhaustive list of all literature pertinent to vitamin D and immunopathology. Instead, we will frame the reasons and rationale behind the development of several immunoregulatory activities for 1,25(OH)2D3. [ABSTRACT FROM AUTHOR]

The paper describes the conditions for handling and exposure to radiation of the experimental animals (Wistar rats) and the methods of statistical processing of the obtained data, which were used to determine the effect of long-term exposure of the animals to radio-frequency electromagnetic fields (2450 MHz) of nonthermal intensity (500 μW/cm) on autoimmune processes; the study was performed under the auspices of the World Health Organization. [ABSTRACT FROM AUTHOR]

Autoimmune inner ear disease probably accounts for less than 1% of all cases of balance disorders, but its incidence is often overlooked due to the absence of a specific diagnostic test. Furthermore, in several systemic autoimmune diseases the vestibulo-cochlear system may be affected. Clinical features comprise generalized imbalance, ataxia, motion intolerance, episodic vertigo and positional vertigo. An autoimmune mechanism seems to be responsible for 6% of unilateral and 16% of bilateral forms of Ménière’s disease. Oscillopsia and disequilibrium secondary to a bilateral vestibular paresis are probably caused by an autoimmune response in 5% of cases. Balance disorders of central origin may be due to other immuno-mediated disorders such as multiple sclerosis, brainstem encephalitis and vasculitidis. Aim of this paper is to assess the clinical features of autoimmune vertigo disorders through a systematic literature review. [ABSTRACT FROM AUTHOR]

Primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) are enigmatic chronic inflammatory diseases of the liver, which are frequently associated with chronic inflammatory bowel diseases. Both types of liver disease share various distinct autoantibodies such as atypical perinuclear antineutrophil cytoplasmic antibodies (p-ANCA), and thus are considered autoimmune disorders with atypical features. The discovery that atypical p-ANCA recognize both tubulin beta isoform 5 in human neutrophils and the bacterial cell division protein FtsZ has renewed the discussion on the potential role of microorganisms in the pathogenesis of both diseases. In this paper, we review the evidence for microbial infection in PSC and AIH and discuss new concepts how cross-recognition between microbial antigens in the gut and host components by the immune system along with stimulation of pattern recognition receptors might give rise to chronic hepatic inflammatory disorders with features of autoimmunity. [ABSTRACT FROM AUTHOR]

Viruses require viral and cellular chaperones during their life cycle and interactions of these molecules with the immune system are probable during the infection. Thus, an anti-chaperone antibody response has been firstly investigated in hepatitis C patients in this paper. A HepG2-lysate antigen (90, 79, 72, 70, 62, 54 and 48 kDa) was assayed in sera from 59 (19F/40M) chronic hepatitis C patients without cirrhosis before therapy. Forty of them were positive for anti-HepG2 lysate antigen antibodies and this test may evaluate biological autoimmunity. Hsp70.1, Hsp90 and calreticulin levels were significantly higher in this antigen than in a control HepG2 antigen. Secondly, Hsp70.1 was identified as Hsp 70 kDa protein-1 by proteomic analysis and studied as a possible antibody target. Fourteen out of 59 patients were positive for anti-Hsp70.1 antibodies that were inversely correlated with alanine aminotransferase levels, the Metavir activity index and viraemia. Finally, for comparative purposes, 50 sera from systemic lupus erythematosus (SLE) patients have been tested: eight and 41 of them were positive for anti-Hsp70.1 and anti-HepG2 lysate antigen antibodies, respectively. Therefore, anti-Hsp70.1 autoantibodies may be produced and can partially lead to biological autoimmunity in chronic hepatitis C patients. [ABSTRACT FROM AUTHOR]

Vitiligo is a common skin and hair depigmentary disorder that results from selective destruction of melanocytes. It occurs in a typical multifactorial, polygenic inheritance. Several studies have indicated that vitiligo is associated with some autoimmune diseases. In this paper we examined 6,516 vitiligo patients including clinical characteristics, familial involvement, and their association with other autoimmune diseases. Compared with sporadic vitiligo probands, familial vitiligo probands have earlier age onset and longer disease duration. The prevalences of four autoimmune diseases namely rheumatoid arthritis, chronic urticaria, alopecia areata and psoriasis, were significantly elevated in generalized vitiligo probands and their first-degree relatives. The prevalences of chronic urticaria, rheumatoid arthritis, psoriasis were much higher in familial generalized vitiligo probands. In addition, the prevalences of diabetes mellitus and asthma were also higher in familial vitiligo probands. These findings indicate that generalized vitiligo may share common genetic aetiologic links with other autoimmune diseases, and the genetic component of familial generalized vitiligo is stronger. [ABSTRACT FROM AUTHOR]

Abstract Introduction  The immune response is controlled by several inhibitory mechanisms. These mechanisms include regulatory T cells, which exist in multiple classes. Notable among these are Foxp3-expressing regulatory T cells (Treg), NKT cells, and Tr1 cells. Common to these mechanisms are inhibitory cytokines such as interleukin-10 and transforming growth factor-beta (TGF-β). TGF-β and Foxp3-expressing Treg cells are critical in maintaining self-tolerance and immune homeostasis. Discussions  The immune suppressive functions of TGF-β and Treg cells are widely acknowledged and extensively studied. Nonetheless, recent studies revealed the positive roles for TGF-β and Treg cells in shaping the immune system and the inflammatory responses. In this paper, we will discuss the role of these mechanisms in the control of immunity and autoimmunity and the mechanisms that underlie how these molecules control these responses. [ABSTRACT FROM AUTHOR]

Inappropriate T cell responses cause the four classical types of hypersensitivity immune reactions. All of these can target the kidney and cause distinct forms of glomerulonephritis. CD4+ T cells can mediate glomerular immunopathology by cytokine secretion, by activating effector cells such as macrophages or by inducing auto-antibodies or immune-complexes. Cytotoxic CD8+ T cell responses and failure of regulatory T cells may represent two additional types of anti-renal hypersensitivity. T cell activation is critically dependent on dendritic cells (DC), whose role in renal disease appears to be protective, but underlying mechanisms are largely unknown. In this paper, we summarized mechanistic information from rodent models on the roles of DC and T cells in glomerular immunopathology. [ABSTRACT FROM AUTHOR]

The most distinctive feature of Alzheimer’s disease (AD) is the specific degeneration of the neurons involved in memory consolidation, storage, and retrieval. Patients suffering from AD forget basic information about their past, loose linguistic and calculative abilities and communication skills. Thus, understanding the etiology of AD may provide insights into the mechanisms of memory and vice versa. The brain is an immunologically privileged site protected from the organism’s immune reactions by the blood–brain barrier (BBB). All risk factors for AD (both cardiovascular and genetic) lead to destruction of the BBB. Evidence emerging from recent literature indicates that AD may have an autoimmune nature associated with BBB impairments. This hypothesis suggests that the process of memory consolidation involves the synthesis of novel macromolecules recognized by the immune system as “non-self” antigens. The objective of this paper is to stimulate new approaches to studies of neural mechanisms underpinning memory consolidation and its breakdown during AD. If the hypothesis on the autoimmune nature of AD is correct, the identification of the putative antigenic macromolecules might be critical to understanding the etiology and prevention of AD, as well as for elucidating cellular mechanisms of learning and memory. [ABSTRACT FROM AUTHOR]