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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]

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]

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]

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]

Objective: This paper reports the clinical manifestation and auxiliary examination features of 15 Chinese patients with glial fibrillary acidic protein (GFAP) autoimmunity. Methods: From June 2016 to December 2019, patients suspected to have neurological autoimmune disease after having their serum and cerebrospinal fluid (CSF) tested for conventional neural antibodies were scanned for additional autoantibodies by immunohistochemistry. Samples that showed a characteristic immunoreactive pattern reminiscent of the GFAP of astrocytes were selected and confirmed by cell-based assay using cells-expressing human GFAPα. Results: A total of 15 patients (eight male and seven female) with a median age at onset of 53 years (range 28–72) were identified as GFAP-IgG-positive. Fourteen cases had GFAP-IgG detected in the CSF, while serum GFAP-IgG was detected in 11 cases. Eleven of the fifteen patients (73.3%) presented with an acute monophasic course, of which 10 (90.9%) had antecedent flu-like symptoms. The predominant phenotype was meningoencephalitis (46.7%), followed by meningoencephalomyelitis in 40% of the cases. The most common clinical features included long tract signs, brainstem symptoms, tremors, headaches, and psychiatric symptoms. Magnetic resonance imaging (MRI) revealed the enhancement of the meninges, the surface of the brainstem, the cerebellum, and the spinal cord as predominant. Inflammatory CSF showed mild lymphocyte-predominant pleocytosis with a median of 51/μL and elevated protein with a median of 87.5 mg/dL. Five patients had coexisting antibodies, including NMDAR-IgG in three patients and Yo and MOG-IgG in one patient each. One patient underwent a stereotactic brain biopsy, and the neuropathology diagnosis was diffuse large B-cell lymphoma. One patient had ovarian teratoma. Eleven of the fifteen (73.3%) patients received both intravenous immunoglobulin and steroids. Among them, three patients also received immunosuppressive agents later. During a two-year follow-up, 9 of the 15 (60%) patients achieved complete clinical remission. Conclusions: The clinical presentation of GFAP astrocytopathy is heterogeneous. It can be characterized by an acute monophasic course and a chronic relapsing course. Tremors are a prominent clinical manifestation in patients with an acute monophasic course with GFAP-IgG antibodies only. Most patients responded well to immunotherapy. In patients with GFAP autoimmunity, presenting with a chronic relapsing course, one should actively search for immunogenic factors and the culprit antibodies. In the case of primary central nervous system lymphoma, GFAP autoimmunity does not always equate to autoimmune GFAP astrocytopathy. [ABSTRACT FROM AUTHOR]

Since the onset of the COVID-19 pandemic, numerous publications have appeared describing autoimmune pathologies developing after a coronavirus infection, with several papers reporting autoantibody production during the acute period of the disease. Several viral diseases are known to trigger autoimmune processes, and the appearance of catalytic antibodies with DNase activity is one of the earliest markers of several autoimmune pathologies. Therefore, we analyzed whether IgG antibodies from blood plasma of SARS-CoV-2 patients after recovery could bind and hydrolyze DNA. We analyzed how vaccination of patients with adenovirus Sputnik V vaccine influences the production of abzymes with DNase activity. Four groups were selected for the analysis, each containing 25 patients according to their relative titers of antibodies to S-protein: with high and median titers, vaccinated with Sputnik V with high titers, and a control group of donors with negative titers. The relative titers of antibodies against DNA and the relative DNase activity of IgGs depended very much on the individual patient and the donor, and no significant correlation was found between the relative values of antibodies titers and their DNase activity. Our results indicate that COVID-19 disease and vaccination with adenoviral Sputnik V vaccine do not result in the development or enhancement of strong autoimmune reactions as in the typical autoimmune diseases associated with the production of anti-DNA and DNA hydrolyzing antibodies. [ABSTRACT FROM AUTHOR]

Much evidence suggests autoimmunity in the etiopathogenesis of periodontal disease. In fact, in periodontitis, there is antibody production against collagen, DNA, and IgG, as well as increased IgA expression, T cell dysfunction, high expression of class II MHC molecules on the surface of gingival epithelial cells in inflamed tissues, activation of NK cells, and the generation of antibodies against the azurophil granules of polymorphonuclear leukocytes. In general, direct activation of autoreactive immune cells and production of TNF can activate neutrophils to release pro-inflammatory enzymes with tissue damage in the gingiva. Gingival inflammation and, in the most serious cases, periodontitis, are mainly due to the dysbiosis of the commensal oral microbiota that triggers the immune system. This inflammatory pathological state can affect the periodontal ligament, bone, and the entire gingival tissue. Oral tolerance can be abrogated by some cytokines produced by epithelial cells and activated immune cells, including mast cells (MCs). Periodontal cells and inflammatory–immune cells, including mast cells (MCs), produce cytokines and chemokines, mediating local inflammation of the gingival, along with destruction of the periodontal ligament and alveolar bone. Immune-cell activation and recruitment can be induced by inflammatory cytokines, such as IL-1, TNF, IL-33, and bacterial products, including lipopolysaccharide (LPS). IL-1 and IL-33 are pleiotropic cytokines from members of the IL-1 family, which mediate inflammation of MCs and contribute to many key features of periodontitis and other inflammatory disorders. IL-33 activates several immune cells, including lymphocytes, Th2 cells, and MCs in both innate and acquired immunological diseases. The classic therapies for periodontitis include non-surgical periodontal treatment, surgery, antibiotics, anti-inflammatory drugs, and surgery, which have been only partially effective. Recently, a natural cytokine, IL-37, a member of the IL-1 family and a suppressor of IL-1b, has received considerable attention for the treatment of inflammatory diseases. In this article, we report that IL-37 may be an important and effective therapeutic cytokine that may inhibit periodontal inflammation. The purpose of this paper is to study the relationship between MCs, IL-1, IL-33, and IL-37 inhibition in acute and chronic inflamed gingival tissue. [ABSTRACT FROM AUTHOR]

Objective: It has been documented that several major components of air pollution, including trace elements and polycyclic aromatic hydrocarbons, are associated with the prevalence of systemic lupus erythematosus (SLE). However, the impact of air pollution on the SLE disease activity is still elusive. In this paper, we review the current evidence investigating the link between air pollution, especially when measured as PM2.5, and SLE severity and activity. Methods: A detailed literature search was applied a priori to the Ovid MEDLINE In-Process and Other Non-Indexed Citation 1986 to present. Presented abstracts from the European League Against Rheumatism and American College of Rheumatology (ACR)/Association for Rheumatology Health Professionals (ARHP) Annual Meetings (2011-2018) were also screened. Results: Out of a total of 1354 papers retrieved from search and references list for detailed evaluation, data from 652 patients with SLE from three studies were analyzed. Two studies had an observational longitudinal design, counting for 348 patients with a follow-up of 24 months and 79 months. Retrieved studies differed for disease activity assessment and air pollution quantifications. Conclusion: Current evidence suggests that variations in air pollution may influence the disease activity in patients with SLE. However, the sample size, methodological biases, and differences across the studies make further research mandatory. Understanding the increased burden of SLE and its complications, not only from a medical, but also from a socio-demographic perspective, including an exposure to pollutants, should have implications for resource allocation and access to subspecialty care. [ABSTRACT FROM AUTHOR]

Sirtuins (SIRTs) represent a class of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases that exert a crucial role in cellular signal transduction and various biological processes. The mammalian sirtuins family encompasses SIRT1 to SIRT7, exhibiting therapeutic potential in counteracting cellular aging, modulating metabolism, responding to oxidative stress, inhibiting tumors, and improving cellular microenvironment. These enzymes are intricately linked to the occurrence and treatment of diverse pathological conditions, including cancer, autoimmune diseases, and cardiovascular disorders. Given the significance of histone modification in gene expression and chromatin structure, maintaining the equilibrium of the sirtuins family is imperative for disease prevention and health restoration. Mounting evidence suggests that modulators of SIRTs play a crucial role in treating various diseases and maintaining physiological balance. This review delves into the molecular structure and regulatory functions of the sirtuins family, reviews the classification and historical evolution of SIRTs modulators, offers a systematic overview of existing SIRTs modulation strategies, and elucidates the regulatory mechanisms of SIRTs modulators (agonists and inhibitors) and their clinical applications. The article concludes by summarizing the challenges encountered in SIRTs modulator research and offering insights into future research directions. [Display omitted] • Sirtuins (SIRTs), as key regulatory factors in cellular processes, are deeply involved in many life processes. • SIRTs modulators have shown great potential in treating various diseases and maintaining physiological balance. • The field of SIRTs and its modulators is developing very rapidly. This paper fills the gap in the research summary of SIRTs modulators in time, and provides valuable insights into the challenges encountered in the research field. [ABSTRACT FROM AUTHOR]

Simple Summary: Since its first description 35 years ago, the transcription factor NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells) has been shown to be a key mediator of immune cell responses to inflammatory mediators, oxidative stress and genotoxic injury. Dysregulated NF-κB signalling drives inflammation in inflammatory disorders such as multiple sclerosis, rheumatoid arthritis or inflammatory bowel disease. Thus, re-establishing the appropriate regulation of NF-κB activity seems like a promising approach to treat inflammatory diseases. Current anti-inflammatory drugs have many, often serious, side effects. Thus, there is an unmet clinical need for safe and effective anti-inflammatory medicines that both decrease inflammatory mediator production and enhance endogenous anti-inflammatory and prorepair pathways. So far, traditional de novo drug discovery has fallen short of satisfying this need. Drug repurposing is a cost- and time-effective alternative to de novo drug development for the identification of novel applications and has already resulted in the identification of effective anti-inflammatories in the ongoing COVID-19 pandemic. In this paper we critically review NF-κB as a potential target for the development of anti-inflammatory drugs with an emphasis on drug repurposing as a strategy to identify new approaches to treat inflammatory diseases. NF-κB is a central mediator of inflammation, response to DNA damage and oxidative stress. As a result of its central role in so many important cellular processes, NF-κB dysregulation has been implicated in the pathology of important human diseases. NF-κB activation causes inappropriate inflammatory responses in diseases including rheumatoid arthritis (RA) and multiple sclerosis (MS). Thus, modulation of NF-κB signaling is being widely investigated as an approach to treat chronic inflammatory diseases, autoimmunity and cancer. The emergence of COVID-19 in late 2019, the subsequent pandemic and the huge clinical burden of patients with life-threatening SARS-CoV-2 pneumonia led to a massive scramble to repurpose existing medicines to treat lung inflammation in a wide range of healthcare systems. These efforts continue and have proven to be controversial. Drug repurposing strategies are a promising alternative to de novo drug development, as they minimize drug development timelines and reduce the risk of failure due to unexpected side effects. Different experimental approaches have been applied to identify existing medicines which inhibit NF-κB that could be repurposed as anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

Linear IgA bullous dermatosis (LABD) is a rare subepidermal autoimmune blistering disease characterized by linear deposition of IgA along the basement membrane zone. Although most reported cases are idiopathic, there is a subset of patients with drug-induced LABD. Various drugs have been associated with the drug-induced form of the disease. This paper reviews the literature on drugs reported to elicit linear IgA dermatosis and its specific clinical presentation. In addition, a case report of a 77-year-old male patient with linear IgA dermatosis induced by vancomycin is described. The aim of this paper is to emphasize the need to include this differential diagnosis in cases of suspected adverse drug reactions, as well as to highlight the role of drugs in LABD. [ABSTRACT FROM AUTHOR]

The immune system employs complex tolerance mechanisms in order to avoid harmful autoimmunity, yet autoantibodies are frequently observed in cancer. In a paper in Cell , Mazor et al. report that autoantibodies produced by tumor-infiltrating B cells in human ovarian cancer frequently recognize the self-protein matrix metalloproteinase 14 (MMP14) through two distinct mechanisms of tolerance disruption. [ABSTRACT FROM AUTHOR]

Summary: Isolated decreased serum‐immunoglobulin (Ig)M has been associated with severe and/or recurrent infections, atopy and autoimmunity. However, the reported high prevalence of clinical problems in IgM‐deficient patients may reflect the skewed tertiary centre population studied so far. Also, many papers on IgM deficiency have included patients with more abnormalities than simply IgM‐deficiency. We studied truly selective primary IgM deficiency according to the diagnostic criteria of the European Society for Immunodeficiencies (ESID) (true sIgMdef) by reviewing the literature (261 patients with primary decreased serum‐IgM in 46 papers) and analysing retrospectively all patients with decreased serum‐IgM in a large teaching hospital in 's‐Hertogenbosch, the Netherlands [1 July 2005–23 March 2016; n = 8049 IgM < 0·4 g/l; n = 2064 solitary (IgG+IgA normal/IgM < age‐matched reference)]. A total of 359 of 2064 (17%) cases from our cohort had primary isolated decreased serum‐IgM, proven persistent in 45 of 359 (13%) cases; their medical charts were reviewed. Our main finding is that true sIgMdef is probably very rare. Only six of 261 (2%) literature cases and three of 45 (7%) cases from our cohort fulfilled the ESID criteria completely; 63 of 261 (24%) literature cases also had other immunological abnormalities and fulfilled the criteria for unclassified antibody deficiencies (unPAD) instead. The diagnosis was often uncertain (possible sIgMdef): data on IgG subclasses and/or vaccination responses were lacking in 192 of 261 (74%) literature cases and 42 of 45 (93%) cases from our cohort. Our results also illustrate the clinical challenge of determining the relevance of a serum sample with decreased IgM; a larger cohort of true sIgMdef patients is needed to explore fully its clinical consequences. The ESID online Registry would be a useful tool for this. [ABSTRACT FROM AUTHOR]

There is increasing evidence from animal and human studies that glaucoma is an autoimmune disease. Evidence for this hypothesis includes the fact that antibodies as well as T‐cell responses to heat‐shock proteins (HSPs) are detectable in some patients with glaucoma and in an animal model of the disease. As in the human disease, experimental animal models of glaucoma have been found to demonstrate neurodegenerative changes in the optic nerve associated with immunoglobulin and T‐cell infiltration. Although there is still insufficient evidence in humans to classify all cases of glaucoma as autoimmune diseases, the implications of this hypothesis have major impact on the diagnosis and treatment of glaucoma. In this paper, we discuss the concept that glaucoma is an autoimmune disease and review emerging evidence for this concept. There is increasing experimental data that some types of normal‐pressure glaucoma may involve immune mechanisms directed at self‐antigens, such as HSP, but proof of the concept that glaucoma is an autoimmune disease remains to be conclusively demonstrated. [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]

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]

Epidemiological studies, animal models, and case-control studies indicate maternal immune activation may be an important factor involved in disease expression of autism spectrum disorder (ASD), Tourette syndrome, and obsessive-compulsive disorder (OCD). We report eight children (mean age 6y 6mo [range 4-15y]; six males and two females) referred over a 2-year period with at least one of these neurodevelopmental disorders plus a maternal history of thyroid autoimmunity. Seven of eight children presented with an abrupt onset of neuropsychiatric symptoms (OCD [n=6], tics [n=5], and/or psychosis [n=1]), associated with an autistic or global regression. Four children had a pre-existing diagnosis of ASD. Six presentations were preceded by infection, and symptoms followed a relapsing-remitting course in seven children. All children responded to immunomodulatory treatment as indicated by a reduction in psychiatric symptoms, and seven children were also managed with conventional treatment with additional improvement. We propose that maternal autoimmunity can activate fetal microglia or alter transcription of neurodevelopmental vulnerability and/or immune genes in utero, and is an environmental factor that increases the expression and severity of neurodevelopmental problems, and susceptibility to deteriorations after infectious or stress stimuli. WHAT THIS PAPER ADDS: Maternal thyroid autoimmunity may represent a risk factor for neuropsychiatric disorders in offspring. Atypical neuropsychiatric features in these children may be due to maternal immune activation in utero. [ABSTRACT FROM AUTHOR]

Biological disease-modifying antirheumatic drugs target specific components of the immune response related to pathogenesis of autoimmune and inflammatory diseases. Introduction of biologic therapies has enabled better disease control than conventional drugs and thus a reduction in comorbidity and mortality. However, there is concern about adverse effects of these drugs including infections, cancers and drug-induced autoimmune diseases. Patients undergoing biologic treatment are at small but significant risk of serious infections. The overall risk of malignancies in patients on biologics compared with the general population is not increased, but there is evidence of a higher risk of individual cancers. Surprisingly, biological treatment may induce autoantibody production and, rarely, development of autoimmune diseases. A growing body of literature has evaluated the risk of adverse effects during biologic therapies. This paper outlines adverse effects of biological disease-modifying antirheumatic drugs related to immune system disorders, both immunodeficiency and autoimmunity. [ABSTRACT FROM AUTHOR]

This paper investigates the dynamics of immune response and autoimmunity with particular emphasis on the role of regulatory T cells (Tregs), T cells with different activation thresholds, and cytokines in mediating T cell activity. Analysis of the steady states yields parameter regions corresponding to regimes of normal clearance of viral infection, chronic infection, or autoimmune behavior, and the boundaries of stability and bifurcations of relevant steady states are found in terms of system parameters. Numerical simulations are performed to illustrate different dynamical scenarios, and to identify basins of attraction of different steady states and periodic solutions, highlighting the important role played by the initial conditions in determining the outcome of immune interactions. [ABSTRACT FROM AUTHOR]

The presence or absence of terminal sialic acid residues in the sugar moiety attached to the Fc-domain of IgG molecules modulates IgG activity and is associated with autoimmune or infection related inflammation. In a recent paper, Oswald and colleagues suggest that IgG sialylation may occur post IgG secretion from plasma cells, which would be a major issue for therapeutic antibodies injected into patients. In contrast, we argue that previous work rather demonstrates that IgG sialylation occurs within B cells and that the experimental system used by the authors is not suitable to address this critical question. [ABSTRACT FROM AUTHOR]

For many years, the role of interleukin-2 (IL-2) in autoimmune responses was established as a cytokine possessing strong pro-inflammatory activity. Studies of the past few years have changed our knowledge on IL-2 in autoimmune chronic inflammation, suggesting its protective role, when administered at low-doses. The disrupted balance between regulatory and effector T cells (Tregs and Teffs, respectively) is a characteristic of autoimmune diseases, and is dependent on homeostatic cytokines, including IL-2. Actually, inherent defects in the IL-2 signaling pathway and/or levels leading to Treg compromised function and numbers as well as Th17 expansion have been attributed to autoimmune disorders. In this review, we discuss the role of IL-2 in the pathogenesis of autoimmune diseases. In particular, we highlight the impact of the dysregulated IL-2 pathway on disruption of the Treg/Th17 balance, reversal of which appears to be a possible mechanism of the low-dose IL-2 treatment. The negative effects of IL-2 on the differentiation of follicular helper T cells (Tfh) and pathogenic Th17 cells, both of which contribute to autoimmunity, is emphasized in the paper as well. We also compare the current IL-2-based therapies of animal and human subjects with immune-mediated diseases aimed at boosting the Treg population, which is the most IL-2-dependent cell subset desirable for sufficient control of autoimmunity. New perspectives of therapeutic approaches focused on selective delivery of IL-2 to inflamed tissues, thus allowing local activity of IL-2 to be combined with its reduced systemic and pleiotropic toxicity, are also proposed in this paper. [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: The B and T cells of the human adaptive immune system leverage a highly diverse repertoire of antigen-specific receptors to protect the human body from pathogens. The sequencing and analysis of immune repertoires is emerging as an important tool to understand immune responses, whether beneficial or harmful (in the case of autoimmunity). However, methods for studying these repertoires, and for directly comparing different immune repertoires, are lacking. Results: In this paper, we present a non-parametric method for directly comparing sequencing repertoires, with the goal of rigorously quantifying differences in V, D, and J gene segment utilization. This method, referred to as the Repertoire Dissimilarity Index (RDI), uses a bootstrapped subsampling approach to account for variance in sequencing depth, and, coupled with a data simulation approach, allows for direct quantification of the average variation between repertoires. We use the RDI method to recapitulate known differences in the formation of the CD4+ and CD8+ T cell repertoires, and further show that antigen-driven activation of naïve CD8+ T cells is more selective than in the CD4+ repertoire, resulting in a more specialized CD8+ memory repertoire. Conclusions: We prove that the RDI method is an accurate and versatile method for comparisons of immune repertoires. The RDI method has been implemented as an R package, and is available for download through Bitbucket. [ABSTRACT FROM AUTHOR]

It is just over 5 years since Clinical and Experimental Immunology came under the direction of a new team of Editors and made a concerted effort to refresh its approach to promoting clinical and applied immunology through its pages. There were two major objectives: to foster papers in a field which, at the time, we loosely termed 'translational immunology'; and to create a forum for the presentation and discussion of immunology that is relevant to clinicians operating in this space. So, how are we doing with these endeavours? This brief paper aims to summarize some of the key learning points and successes and highlight areas in which translational gaps remain. [ABSTRACT FROM AUTHOR]

As the amount of biomedical information available in the literature continues to increase, databases that aggregate this information continue to grow in importance and scope. The population of databases can occur either through fully automated text mining approaches or through manual curation by human subject experts. We here report our experiences in populating the National Institute of Allergy and Infectious Diseases sponsored Immune Epitope Database and Analysis Resource ( IEDB, http://iedb.org), which was created in 2003, and as of 2012 captures the epitope information from approximately 99% of all papers published to date that describe immune epitopes (with the exception of cancer and HIV data). This was achieved using a hybrid model based on automated document categorization and extensive human expert involvement. This task required automated scanning of over 22 million PubMed abstracts followed by classification and curation of over 13 000 references, including over 7000 infectious disease-related manuscripts, over 1000 allergy-related manuscripts, roughly 4000 related to autoimmunity, and 1000 transplant/alloantigen-related manuscripts. The IEDB curation involves an unprecedented level of detail, capturing for each paper the actual experiments performed for each different epitope structure. Key to enabling this process was the extensive use of ontologies to ensure rigorous and consistent data representation as well as interoperability with other bioinformatics resources, including the Protein Data Bank, Chemical Entities of Biological Interest, and the NIAID Bioinformatics Resource Centers. A growing fraction of the IEDB data derives from direct submissions by research groups engaged in epitope discovery, and is being facilitated by the implementation of novel data submission tools. The present explosion of information contained in biological databases demands effective query and display capabilities to optimize the user experience. Accordingly, the development of original ways to query the database, on the basis of ontologically driven hierarchical trees, and display of epitope data in aggregate in a biologically intuitive yet rigorous fashion is now at the forefront of the IEDB efforts. We also highlight advances made in the realm of epitope analysis and predictive tools available in the IEDB. [ABSTRACT FROM AUTHOR]

After an acute ischemic stroke (AIS), inflammatory processes are able to concomitantly induce both beneficial and detrimental effects. In this narrative review, we updated evidence on the inflammatory pathways and mediators that are investigated as promising therapeutic targets. We searched for papers on PubMed and MEDLINE up to August 2016. The terms searched alone or in combination were: ischemic stroke, inflammation, oxidative stress, ischemia reperfusion, innate immunity, adaptive immunity, autoimmunity. Inflammation in AIS is characterized by a storm of cytokines, chemokines, and Damage-Associated Molecular Patterns (DAMPs) released by several cells contributing to exacerbate the tissue injury both in the acute and reparative phases. Interestingly, many biomarkers have been studied, but none of these reflected the complexity of systemic immune response. Reperfusion therapies showed a good efficacy in the recovery after an AIS. New therapies appear promising both in pre-clinical and clinical studies, but still need more detailed studies to be translated in the ordinary clinical practice. In spite of clinical progresses, no beneficial long-term interventions targeting inflammation are currently available. Our knowledge about cells, biomarkers, and inflammatory markers is growing and is hoped to better evaluate the impact of new treatments, such as monoclonal antibodies and cell-based therapies. [ABSTRACT FROM AUTHOR]

Thymic epithelial cells (TECs) play a key role in the regulation of central immune tolerance by expressing autoantigens and eliminating self-reactive T cells. In a previous paper we reported that adrenomedullin (ADM) and its co-receptor protein RAMP2 are located intracellularly in newborn human thymic epithelial cells (TECs). This work has two main aims: (1) to examine the cellular localization of ADM and its receptor in TECs of adult Wistar rats to validate this animal model for the study of the ADM system and its function(s) in thymus; (2) to investigate the potential modulating effect of ADM on the NF-kB pathway, which is involved through the production of cytokines such as IL-6, in the maturation of T-lymphocytes and immunological tolerance. Our results show that, similarly to human newborn TECs, ADM is localized to the cytoplasm of adult rat TECs, and RAMP2 is expressed in the nucleus but not in the plasma membrane. Pretreatment of TECs for 4 h with ADM significantly reduced lipopolysaccharide (LPS)-induced release of IL-6 (P < 0.001) and expression of the p65 subunit of NF-kB, while doubled the expression of IkBα (P < 0.001), the physiological inhibitor of NF-kB nuclear translocation. These effects were not mediated by activation of the cAMP pathway, a signalling cascade that is rapidly activated by ADM in cells that express plasma membrane RAMP2, but were the consequence of a reduction in the transcription of p65 (P < 0.001) and an increase in the transcription of IkBα (P < 0.05). On the basis of these findings we propose that in rat TECs ADM reduces IL-6 secretion by modulating NF-kB genes transcription through an interaction with a receptor localized to the nucleus. This may partly explain the protective effects of ADM in autoimmune diseases and points to the ADM system of TECs as a novel potential target for immunomodulating drugs. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, and CD4+ T cells formthe core immunopathogenic cascade leading to chronic inflammation. Traditionally, Th1 cells (interferon-γ-producing CD4+ T cells) driven by interleukin 12 (IL12) were considered to be the encephalitogenic T cells in MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Currently, Th17 cells (Il17-producing CD4+ T cells) are considered to play a fundamental role in the immunopathogenesis of EAE. This paper highlights the growing evidence that Th17 cells play the core role in the complex adaptive immunity of EAE/MS and discusses the roles of the associated immune cells and cytokines. These constitute the modern immunological basis for the development of novel clinical and preclinical immunomodulatory therapies for MS discussed in this paper. [ABSTRACT FROM AUTHOR]

Recent papers published had suggested the association of malignancy with autoimmune disease. Numerous autoimmune phenomena have been reported in cancer patients. There is a bidirectional relationship between autoimmunity and malignancy. Patients with autoimmune conditions develop neoplastic diseases and, analogously, various autoantibodies have been detected in the sera of patients with hematological and epithelial malignancies. A wide variety of cancer types have been associated with the autoimmune disorders, which raises a question about immune reactions to the tumor as a cause of the autoimmune disorder. It was suggested that the generation of autoantibodies in malignant conditions is an aspect of immune deficiency or an immune response against proteins which are involved in proliferative functions. The intent of this paper is not to provide a comprehensive review of autoimmunity and malignancy but rather to illustrate the relationship between autoimmunity and malignancy. [ABSTRACT FROM AUTHOR]

Ionizing radiation has the potential to cause extensive damage to living organisms. It can directly act on DNA, proteins and lipids, resulting in ionizing excitation and chemical bond cleavage, which can lead to molecular and cellular damage. Ionizing radiation can hydrolyze water molecules in the body, resulting in increased numbers of free radicals with strong oxidation ability. This process indirectly leads to tissue degeneration and necrosis, which can possibly result in cancer. In this paper, the intervention mechanism of flavonoids on ionizing radiation was analyzed. It has been revealed that the intervention mechanism associated with flavonoids may offer protective properties for DNA, prevent scavenging free radicals, and protect against auto-immune damage. In addition, this invention mechanism can protect the hematopoietic system and reduce inflammation. [ABSTRACT FROM AUTHOR]

The development and progression of systemic lupus erythematosus is mediated by the complex interaction of genetic and environmental factors. To decipher the genetics that contribute to pathogenesis and the production of pathogenic autoantibodies, our lab has focused on the generation of congenic lupus-prone mice derived from the New Zealand Black (NZB) strain. Previous work has shown that an NZB-derived chromosome 4 interval spanning 32 to 151 Mb led to expansion of CD5+ B and Natural Killer T (NKT) cells, and could suppress autoimmunity when crossed with a lupus-prone mouse strain. Subsequently, it was shown that CD5+ B cells but not NKT cells derived from these mice could suppress the development of pro-inflammatory T cells. In this paper, we aimed to further resolve the genetics that leads to expansion of these two innate-like populations through the creation of additional sub-congenic mice and to characterize the role of IL-10 in the suppression of autoimmunity through the generation of IL-10 knockout mice. We show that expansion of CD5+ B cells and NKT cells localizes to a chromosome 4 interval spanning 91 to 123 Mb, which is distinct from the region that mediates the majority of the suppressive phenotype. We also demonstrate that IL-10 is critical to restraining autoantibody production and surprisingly plays a vital role in supporting the expansion of innate-like populations. [ABSTRACT FROM AUTHOR]

The autoimmune type 1 diabetes mellitus results from immunemediated destruction of pancreatic beta cells. The mechanisms involved in the destruction of β cells are still unclear, it is believed that these autoantigens from the lesion cells are recognized by the immune system, during a non-regulated immune response induces the process of organ-specific autoimmunity. It is necessary to determine exactly which factors are related to the induction of autoimmunity to obtain a better control of the disease. This paper describes the main immunological mechanisms involved in the pathogenesis of type 1 diabetes mellitus, highlighting the involvement of environmental factors (infections) and apoptotic disorders may be related to the release of autoantigen of pancreatic β cells which are recognized and captured by macrophages and dendritic cells and presented to the B lymphocytes and T lymphocytes, which after specific activation by autoantigen generate an autoimmune response organ-specific able to eliminate pancreatic β cells. A better understanding of immunopathogenics mechanisms may contribute to the development of new therapeutic perspectives. [ABSTRACT FROM AUTHOR]

Autoimmune bullous diseases represent a diagnostic challenge due to the wide spectrum of pathologies that share similar clinical features. This paper reports the case of a woman admitted with a supposed diagnosis of a Stevens-Johnson syndrome, in which the history, the profile of autoimmunity and interdisciplinary approach were of vital importance to clarify the clinical picture. [ABSTRACT FROM AUTHOR]

A failure of central immune tolerance driven by autoantigen specific T regulatory (Treg) cells is a major cause of many autoimmune diseases. Restoration of proper autoantigen Treg specific response holds promise as a highly effective, long-term therapy for a wide variety of autoimmune diseases. Generating autoantigen specific Tregs remains a challenge due to the non-specific nature of most tolerizing agents and the complexities of generating Tregs in vivo. Here we show a new push/pull method for inducing antigen-specific Treg tolerance via induction of tolerogenic dendritic cells (tolDCs). We identified a combination of three tolerogenic drugs, dexamethasone, simvastatin and SC-514, which when used in combination with toll-like-receptor (TLR) agonists induces an active tolDC phenotype. When the tolerogenic combination was packaged into a liposome with a model antigen such as ovalbumin (OVA), these tolDCs induce differentiation of OVA specific Tregs both ex vivo and in vivo. We examined the tolerizing potential of the combination in an experimental autoimmune encephalomyelitis (EAE) disease model. Given the antigen specificity of this technique, this paper presents an attractive preclinical autoimmune therapy. [ABSTRACT FROM AUTHOR]

The authors comment on two papers in "Diabetes" journal which offer information on the potential roles of enteroviruses specifically group B coxsackieviruses (CVB) in modulating susceptibility to type 1 diabetes (T1D) development. One of the papers has revealed that CVB B1 (CVB1) was associated with an increased risk of ß-cell autoimmunity. The papers also found an association between infections by CVB3 and CVB6 and a reduced risk of ß-cell autoimmunity.

Anti-centriolar pattern of staining by indirect immunofluorescence (IIF) on human epithelial type 2 (Hep2) cells is rarely observed, mostly in association with scleroderma and scleroderma-like connective tissue disorders. This paper describes four patients with anti-centriole antibody positivity along with a review of the available literature. In this retrospective study, a total of four cases whose serum showed the centriolar pattern on Hep2 cell lines during IIF examination were reviewed. The presence of anti-centriole antibody in the serum should herald the diagnosis of scleroderma spectrum; Raynaud's phenomenon and pulmonary arterial hypertension should be specifically looked for. In the absence of features of autoimmunity, patients should be screened for Mycoplasma infection. [ABSTRACT FROM AUTHOR]

Trichinella spiralis has the unique ability to make itself “at home” by creating and hiding in a new type of cell in the host body that is the nurse cell. From this immunologically privileged place, the parasite orchestrates a long-lasting molecular cross talk with the host through muscle larvae excretory-secretory products (ES L1). Those products can successfully modulate parasite-specific immune responses as well as responses to unrelated antigens (either self or nonself in origin), providing an anti-inflammatory milieu and maintaining homeostasis. It is clear, based on the findings from animal model studies, that T. spiralis and its products induce an immunomodulatory network (which encompasses Th2- and Treg-type responses) that may allow the host to deal with various hyperimmune-associated disorders as well as tumor growth, although the latter still remains unclear. This review focuses on studies of the molecules released by T. spiralis, their interaction with pattern recognition receptors on antigen presenting cells, and subsequently provoked responses. This paper also addresses the immunomodulatory properties of ES L1 molecules and how the induced immunomodulation influences the course of different experimental inflammatory and malignant diseases. [ABSTRACT FROM AUTHOR]

Alopecia areata (AA) is an inflammatory and autoimmune disease presenting with non-scarring hair loss. The aethiopathogenesis of alopecia areata is unclear and many factors including autoimmunity, genetic predisposition, emotional and environmental stress are thought to play important roles in its development. Antioxidant/ oxidant balance perturbation is a common feature in autoimmune, emotional and environmental stress. Therefore, our paper discusses the implications of oxidative stress in alopecia areata. [ABSTRACT FROM AUTHOR]

Vitiligo is an autoimmune disease of the skin that is characterized by patchy depigmentation (i.e., white spots) and results from the loss of melanocytes, which are pigment-producing cells. The pathogenesis of human vitiligo consists of an interaction between intrinsic melanocyte defects, environmental factors, and autoimmune mechanisms that target these cells for destruction. Human clinical and translational studies have outlined pathways that are important in human disease; however, combining human correlative studies with mechanistic studies in representative preclinical animal models is a powerful approach to study disease pathogenesis and develop new treatments. Because of the complex pathogenesis of vitiligo, it is unlikely that any one single animal model will adequately reflect all factors implicated in the initiation, progression, and maintenance of the disease. Therefore, vitiligo is best modeled by multiple systems—each with its strengths and weaknesses—that allow insight into specific components of vitiligo pathogenesis. In this paper, we describe some of the available animal models that have been developed to study vitiligo. [ABSTRACT FROM AUTHOR]

Despite major advances in understanding genetic predispositions ('first hits'), pathogenic immune responses, and the mediators of tissue injury in glomerulonephritis (GN), there remains a dearth of knowledge about the etiologic events, or 'second hits', which trigger these diseases. This paper reviews evidence that infections initiate most forms of GN through numerous simultaneous and/or sequential pathways that begin with activation of the innate immune response and lead to autoimmunity. These pathways include immune dysregulation, adjuvant or bystander effects, epitope spreading, molecular mimicry, epitope conformational changes, and antigen complementarity that, in genetically susceptible individuals, result in the nephritogenic autoimmune responses that underlie GN. Infections may also have direct effects on glomerular cells. Rapid expansion in knowledge of the microbiome and its role in health and disease, as well as systems biology approaches to glomerular disease offer the potential to develop preventive approaches to GNs that can now be treated only with immunosuppression. [ABSTRACT FROM AUTHOR]

Human Th17 pro-inflammatory cells are currently defined as cells that produce IL-17A and F, tumor necrosis factor (TNF)-a, IL-6, IL-21, IL-22 and IL-23. Recently discovered related molecules are forming a family of cytokines, the IL-17 family, IL-17A, IL-17B, IL-17C, IL-17D, IL-17E and IL-17F . The associated receptors for the IL-17 family identified are IL-17R, IL-17RH1, IL-17RL (receptor like), IL-17RD and IL-17RE. This review introduces the roles of IL-17 and Th17 cells in human autoimmune diseases. Studies have shown that T cells with inflammatory effects on epithelial, endothelial and fibroblast cells express IL-17. Th17 cells are supposed to be involved in various autoimmune diseases, such as rheumatoid arthritis, psoriasis, multiple sclerosis, and inflammatory bowel diseases. Base on the biologic functions and regulation, IL-17 has regulatory roles in host defense and chronic inflammation which result in tissue damage and autoimmunity. So the IL-17 links links innate and adaptive immunity and has both beneficial and pathological effects on the immune system. This paper will focus on the possible roles of IL-17 in autoimmune diseases, a fundamental player in immune regulation. [ABSTRACT FROM AUTHOR]

Heat shock proteins ( HSPs) serve as molecular chaperones for diverse client proteins in many biological processes. In plant immunity, cytosolic HSP90s participate in the assembly, stability control and/or activation of immune receptor complexes. In this paper we report that in addition to the well-established positive roles that HSP90 isoforms play in plant immunity, they are also involved in the negative regulation of immune receptor accumulation. Point mutations in two HSP90 genes, HSP90.2 and HSP90.3, were identified from a forward genetic screen designed to isolate mutants with enhanced disease resistance. We found that specific mutations in HSP90.2 and HSP90.3 lead to heightened accumulation of immune receptors, including SNC1, RPS2 and RPS4. HSP90s may assist SGT1 in the formation of SCF E3 ubiquitin ligase complexes that target immune receptors for degradation. Such regulation is critical for maintaining appropriate levels of immune receptor proteins to avoid autoimmunity. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that murine peritoneal cavity-derived B-1a cells possess similarities with described regulatory B cell subsets. The aim of the current study was to examine the potential immunoregulatory function of peritoneal cavity-derived B(-1a) cells. In vitro activation of peritoneal cavity-derived B- and B-1a cells shows that activation of these B cells with anti-CD40 and LPS induces these cells to secrete more IL-10, IL-6 and IgM as compared to splenic B cells. In a suppression assay, CD40/TLR4-activated peritoneal cavity B cells possess regulatory B cell functions as they inhibit the capacity of CD4+ T cells to produce both tumor necrosis factor-α and interferon-γ. Splenic B cells did not show this, whereas non-activated peritoneal cavity B cells augmented the capacity of CD4+ T cells to produce tumor necrosis factor-α, while the ability to produce interferon-γ was not altered. The current paper compares splenic B cells to peritoneal cavity B(-1a) cells in an in vitro activation- and an suppression-assay and concludes that peritoneal cavity B(-1a) cells possess properties that appear similar to splenic autoimmune-suppressive regulatory B cell subsets described in the literature. [ABSTRACT FROM AUTHOR]

Lyme disease has become a global public health problem and a prototype of an emerging infection. Both treatment-refractory infection and symptoms that are related to Borrelia burgdorferi infection remain subject to controversy. Because of the absence of solid evidence on prevalence, causes, diagnostic criteria, tools and treatment options, the role of autoimmunity to residual or persisting antigens, and the role of a toxin or other bacterial-associated products that are responsible for the symptoms and signs, chronic Lyme disease (CLD) remains a relatively poorly understood chronic disease construct. The role and performance of family medicine in the detection, integrative treatment, and follow-up of CLD are not well studied either. The purpose of this paper is to describe insights into the complexity of CLD as a multidimensional chronic disease construct and its relevance to family medicine by means of a systematic literature review. [ABSTRACT FROM AUTHOR]

An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta with a diameter of at least 3.0 cm. AAAs are often asymptomatic and are discovered as incidental findings in imaging studies or when the AAA ruptures leading to a medical emergency. AAAs are more common in males than females, in individuals of European ancestry, and in those over 65 years of age. Smoking is the most important environmental risk factor. In addition, a positive family history of AAA increases the person's risk for AAA. Interestingly, diabetes has been shown to be a protective factor for AAA in many large studies. Hallmarks of AAA pathogenesis include inflammation, vascular smooth muscle cell apoptosis, extracellular matrix degradation, and oxidative stress. Autoimmunity may also play a role in AAA development and progression. In this Outlook paper, we summarize our recent studies on AAA including clinical studies related to surgical repair of AAA and genetic risk factor and large-scale gene expression studies. We conclude with a discussion on our research projects using large data sets available through electronic medical records and biobanks. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) play an important role in both immunological tolerance and immunity as well as in pro- and anti-inflammatory responses. Upon uptake of apoptotic cells and apoptotic bodies, DCs degrade self antigens from them and induce anti-inflammatory response and T regulatory (Treg) cells resulting in the maintenance of tolerance to self antigens. Ageing is characterized by progressive immunodeficiency, inflammation, and autoimmunity. In this paper we will review the role of DCs in inflammation and autoimmunity in human ageing and will highlight the observations that DCs from aged humans display impairment in their capacity to uptake apoptotic cells, and paradoxically induce proinflammatory response and increased reactivity to self antigen (DNA). DNA from aged is hypomethylated and hypomethylation is associated with increased immunogenecity of self DNA. [ABSTRACT FROM AUTHOR]

The identification of phenotype descriptions in the scientific literature, case reports and patient records is a rewarding task for bio-medical text mining. Any progress will support knowledge discovery and linkage to other resources. However because of their wide variation a number of challenges still remain in terms of their identification and semantic normalisation before they can be fully exploited for research purposes. This paper presents novel techniques for identifying potential complex phenotype mentions by exploiting a hybrid model based on machine learning, rules and dictionary matching. A systematic study is made of how to combine sequence labels from these modules as well as the merits of various ontological resources. We evaluated our approach on a subset of Medline abstracts cited by the Online Mendelian Inheritance of Man database related to auto-immune diseases. Using partial matching the best micro-averaged F-score for phenotypes and five other entity classes was 79.9%. A best performance of 75.3% was achieved for phenotype candidates using all semantics resources. We observed the advantage of using SVM-based learn-to-rank for sequence label combination over maximum entropy and a priority list approach. The results indicate that the identification of simple entity types such as chemicals and genes are robustly supported by single semantic resources, whereas phenotypes require combinations. Altogether we conclude that our approach coped well with the compositional structure of phenotypes in the auto-immune domain. [ABSTRACT FROM AUTHOR]