Symptoms Of Autoimmune Disease Research Articles

Microbiome, Autoimmune Diseases and HIV Infection: Friends or Foes?

Several studies highlighted the importance of the interaction between microbiota and the immune system in the development and maintenance of the homeostasis of the human organism. Dysbiosis is associated with proinflammatory and pathological state-like metabolic diseases, autoimmune diseases and HIV infection. In this review, we discuss the current understanding of the possible role of dysbiosis in triggering and/or exacerbating symptoms of autoimmune diseases and HIV infection. There are no data about the influence of the microbiome on the development of autoimmune diseases during HIV infection. We can hypothesize that untreated patients may be more susceptible to the development of autoimmune diseases, due to the presence of dysbiosis. Eubiosis, re-established by probiotic administration, can be used to reduce triggers for autoimmune diseases in untreated HIV patients, although clinical studies are needed to evaluate the role of the microbiome in autoimmune diseases in HIV patients.

Economic Analysis of the Use of Anti-DFS70 Antibody Test in Patients with Undifferentiated Systemic Autoimmune Disease Symptoms.

In patients with antinuclear antibodies (ANA) and undifferentiated features of systemic autoimmune disease, the coexistence of monospecific anti-dense fine speckled 70 (anti-DFS70) antibodies is associated with a lower risk of progression to overt disease. Therefore, they might help in correctly classifying ANA- positive patients and avoiding unnecessary followup diagnostic procedures. The aim of this study was to analyze the economic effect of the introduction of the anti-DFS70 antibody test in a hospital setting. A case-control study was performed to detect monospecific anti-DFS70 antibodies in ANA-positive subjects with undifferentiated features (cases, n = 124) and with a defined systemic autoimmune disease (controls, n = 290). Based on current clinical practice, a decision tree was developed to represent the disease course of patients with undifferentiated features in the subsequent 3 years. A budget impact analysis (BIA) was performed to estimate the effect of implementing the screening for anti-DFS70 antibodies in the case group on the total costs. A sensitivity analysis was conducted to calculate the effect of the uncertainty of the input variables on the results. Among the 124 patients in the case group, 5 (4.0%) tested positive for anti-DFS70 antibodies versus 4/290 (1.4%) in the control group (p = not significant). The mean cost per patient under the current clinical practice decreased from €3274 to €3192 in our scenario. The BIA reports cost savings of €10,128. The introduction of anti-DFS70 antibody test would avoid unnecessary followup diagnostic procedures and minimize the use of health resources generated by suspicion of a potential systemic autoimmune disease.

Experimental models of dermatological diseases

This review presents analysis of experimental models of atopic dermatitis, psoriasis, skin symptoms of autoimmune systemic connective tissue diseases, and blistering skin diseases. Presented in the review are experimental models of atopic dermatitis which reproduce various stages and types of disease that allows the investigation of disease pathogenesis. Atopic dermatitis can develop spontaneously in Nc/Nga mice. There are atopic dermatitis models initiated by monoclonal IgE injection or epicutant sensitization under dermal barrier disfunction imitation. Genetically modified atopic dermatitis models - transgenic and knockout mice – are convenient for investigation of disease stages, cytokines, antigen-presenting cells and T-cells influence. We show that the psoriasis models created by genetic engineering methods are the most convenient for investigation of the role of particular cell types and specific factors in the disease development. Up-regulation of adhesion molecules, cytokines, transcription factors, inflammation mediators in both keratinocytes and immune cells of transgenic mice reveals their influence on psoriasis pathogenesis. There are descriptions of skin symptom models of autoimmune systemic connective tissue diseases and blistering skin disease models with and without genetic modifications. Each model demonstrates some peculiarities of pathogenesis and disease symptoms, whereas combined use of the models will allow to study the mechanisms of development of atopic dermatitis, psoriasis, blistering skin diseases and skin lesions under autoimmune systemic connective tissue diseases, that will contribute to the development of modern effective methods of treatment.

Antiviral Adaptor MAVS Promotes Murine Lupus With a B Cell Autonomous Role.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by increased production of autoantibodies, which commonly target nuclear antigens, and concomitant deposition of immune complexes that cause inflammation in tissues. SLE is often associated with increased systemic expression of type I interferons, in some cases due to dysregulation in nucleic acid-sensing innate pathways. There is strong genetic evidence for a link between cytoplasmic RNA sensing pathways (RIG-I/MDA5) and SLE, both in human patients and murine models, however questions still remain regarding pathway initiation, cell types involved and downstream effects. Here we show that MAVS, an essential adaptor for RIG-I/MDA5 signaling, is necessary for all symptoms of autoimmune disease that develop spontaneously in the lupus model FcγRIIB−/− mice. This effect was independent of type I interferon signaling, TLR7 expression or STING, all three factors that have been connected to autoimmunity. Mixed bone marrow reconstitution experiments showed reduced occurrence in autoimmune germinal centers and diminished autoantibody production by MAVS-deficient B cells. Thus, MAVS plays a B cell intrinsic role in autoreactive B cell activation that is independent of its anti-viral functions and independent of elevated type I interferon expression.

Biologics in rheumatology

Monoclonal antibodies and fusion proteins were introduced into clinical rheumatology 20 years ago. Nowadays they are an established component of modern internal medical practice. This article gives an overview of the breadth of biologics currently in clinical use. Evaluation of published approval studies and guideline recommendations, discussion of the immunological principles and targets in the treatment with biologics. Monoclonal antibodies and fusion proteins for influencing cytokine signals, T‑cell costimulation and B‑cell function are the most important innovations in the treatment of rheumatological diseases. Nowadays they are indispensible for the treatment of moderate and severe disease courses of rheumatoid arthritis, spondylarthropathies and vasculitides. Although a cure or permanent freedom from symptoms in rheumatological autoimmune diseases is still not possible, much more favorable disease courses with less long-term limitations can be achieved by the early administration of biologics.

Autoimmunity Predisposition in Girls With Turner Syndrome.

Background: Turner Syndrome is associated with an increased risk of autoimmune diseases, such as autoimmune thyroiditis, coeliac disease, type 1 diabetes mellitus, inflammatory bowel disease, alopecia areata, or vitiligo. The presence of isochromosome iXq and exposure to estradiol may contribute to the development of the autoimmune process. The aim of this study was to determine the prevalence of autoimmune diseases in a group of TS patients and to assess the impact of karyotype and puberty on the development of autoimmune diseases.Patients and Methods: The analysis encompassed clinical and biochemical data of 134 patients treated between 2001 and 2018. All the patients were examined for autoimmune disease symptoms and tested for the presence of antithyroperoxidase (anti-TPO) and antithyreoglobulin (anti-TG) antibodies. In 73 of the patients, anti-transglutaminase (anti-tTG) antibodies were measured. Thyroid function was assessed by measuring TSH and fT4 levels.Results: The mean follow-up was 5.7 ± 3 years. An autoimmune disease was diagnosed in 46 (34.3%) patients: 39 (29.1%) had only one disorder, whilst 7 (5.2%) presented two disorders. The most common disorder, observed in 40 (29.9%) patients, was thyroid autoimmunity. Hashimoto disease was diagnosed in 20 (14.9%) patients. Of the 73 patients tested for coeliac disease, 4 (5.5%) had anti-tTG and 2 (2.7%) presented overt coeliac disease. Vitiligo was diagnosed in 3 (2.2%) patients, type 1 diabetes mellitus or psoriasis were diagnosed in 2 (1.5%) patients, whilst alopecia areata or lichen sclerosus were diagnosed in 1 (0.7%) patient. The impact of karyotype or estradiol exposure on developing autoimmune diseases were not statistically significant.Conclusions: Our study showed a higher incidence of autoimmune diseases in TS, which is in line with the literature; however, the impact of iXq, or spontaneous/inducted puberty was not confirmed.

Paraneoplastic dermatomyositis appearing after nivolumab therapy for gastric cancer: a case report

BackgroundWhile dermatomyositis is often associated with malignancy, several autoimmune diseases like myositis can be caused by immune checkpoint inhibitors. Differentially diagnosing malignancy-associated dermatomyositis or myositis caused by immune checkpoint inhibitors is sometimes difficult, particularly when a patient with malignancy shows the symptoms of myositis after checkpoint inhibitor administration. We experienced such a case in which we had difficulties in diagnosing paraneoplastic dermatomyositis or drug-associated myositis. In this case, all of our team initially assumed that the diagnosis was myositis caused by immune checkpoint inhibitors. However, it turned out finally that the diagnosis was paraneoplastic dermatomyositis. Because the diagnosis was unexpected, we report here.Case presentationWe report the case of a 71-year-old Japanese man who developed clinical symptoms of myositis, such as muscle aches and weakness, after initiation of nivolumab therapy for his gastric cancer. He was initially diagnosed with nivolumab-induced myositis, because the myositis symptoms appeared after nivolumab administration, and nivolumab is known to trigger various drug-associated autoimmune diseases. However, according to his characteristic skin lesions, the type of muscle weakness, his serum marker profiles, electromyography of his deltoid muscle, and magnetic resonance imaging, he was finally diagnosed as having paraneoplastic dermatomyositis. Accordingly, treatment with intravenously administered corticosteroid pulse treatment, immunoglobulin injection, and tacrolimus was applied; his symptoms subsequently improved. However, to our regret, at day 142 after administration, he died due to rapid worsening of his gastric cancer.ConclusionDifferentially diagnosing paraneoplastic dermatomyositis or drug-associated myositis caused by immune checkpoint inhibitors is difficult in some cases. The differential diagnosis is crucial because it influences the decision regarding the appropriateness of the use of immunosuppressive treatment against the autoimmune diseases as well as the decision regarding the appropriateness of the continuous use of immune checkpoint inhibitors against the primary cancers. Because subclinical autoimmune disease may become overt after administering immune checkpoint inhibitors, non-apparent autoimmune diseases, which have already existed, should also be considered to avoid the delay of appropriate treatment, when symptoms of autoimmune diseases are recognized.

Six Week Raw Vegan Nutrition Protocol Rapidly Reverses Lupus Nephritis: A Case Series

There is a strong body of evidence suggesting that plant-based diets are beneficial for reducing mortality and metabolic risk. Although less studied, plant-based diets may also have great potential for managing symptoms of autoimmune disease, such as systemic lupus erythematosus (sle). This case series details 2 patients with SLE-related nephritis: a 24-year-old female (Case 1) and a 41-year old-male (Case 2). Upon adopting a customized, raw, whole-food, plant-based (WFPB) eating regimen, high in leafy greens and cruciferous vegetables, omega-3 polyunsaturated fatty acids, and water, Case 1’s estimated glomerular filtration rate (eGFR)—a measure of kidney function—increased from 14 to 27 ml/min in 6 weeks, and it was determined that she no longer needed dialysis or a kidney transplant. Her energy and joint pain levels also significantly improved. Similarly, Case 2’s symptoms resolved and laboratory tests were normalized on the diet. However, this patient experienced challenges with adhering to the diet, and it was clear that whenever he deviated from it, symptoms reappeared and eGFR worsened. Potential mechanisms underpinning this improvement include reduced inflammation, fueled by omega-3 intake, and improvements in oxidative stress, fueled by intake of antioxidant-rich fruits and vegetables. These 2 cases experienced significant improvements due to dietary changes alone, suggesting that researchers may consider a randomized trial of raw, WFPB diets as a means of managing SLE.

Early Peritoneal CC Chemokine Production Correlates with Divergent Inflammatory Phenotypes and Susceptibility to Experimental Arthritis in Mice.

The inflammatory and autoimmune events preceding clinical symptoms in rheumatoid arthritis (RA) and other autoimmune diseases are difficult to study in human patients. Therefore, animal models that share immunologic and clinical features with human RA, such as pristane-induced arthritis (PIA), are valuable tools for assessing the primordial events related to arthritis susceptibility. PIA-resistant HIII and susceptible LIII mice were injected i.p. with pristane, and peritoneal lavage fluid was harvested in the early (7 days) and late (35 days) preclinical phases of PIA. Chemokine and cytokine levels were measured in lavage supernatant with ELISA, peritoneal inflammatory leukocytes were immunophenotyped by flow cytometry, and gene expression was determined by qRT-PCR. Leukocyte recruitment was quantitatively and qualitatively divergent in the peritoneum of HIII and LIII mice, with an early increase of CC chemokines (CCL2/CCL3/CCL5/CCL12/CCL22) in the susceptible LIII strain. Also, cytokines such as IL-12p40, IL-23, and IL-18 were elevated in LIII mice while IL-6 was increased in HIII animals. The results show that an early peritoneal CC chemokine response is an important feature of arthritis susceptibility and defines potential biomarkers in this model.

Redox- and bio-activity of apocynin (acetovanillone) in tobacco, a plant phenolic that alleviates symptoms of autoimmune diseases in animals

Apocynin (APO) was shown to be the major constituent of early herbal medicines used to reduce painful suffering from many ailments. Because of its proven utility in rat models, it is now an active candidate for treating humans for several major autoimmune diseases such as Alzheimer's, arthritis, and cardiovascular diseases. In plant research, APO is referred to as acetovanillone, a secondary metabolite that is induced in the leaf apoplast during bacterial invasion. Since its role in plants is unknown, we examined whether any of the attributes found in medical studies could found in plants. In medical studies, APO is considered to be an NADPH oxidase (NOX) inhibitor, however when tested in tobacco suspension cells, APO failed to inhibit NOX activity. In addition, when APO was used to pretreat plants against virulent or avirulent pathovars of Pseudomonas syringae, there was no reduction of symptoms. When pathovars were incubated with 100 μM APO for 90 min, there was only a slight decrease in the bacterial population, suggesting that it was not toxic. In animals, a key step for the inhibition of NOX by APO appears to be its oxidation by myeloperoxidase, yielding dimers and trimers. In vitro studies using pH 6, which is more comparable the plant environment, APO oxidation by horseradish peroxidase yielded similar products. We monitored the redox potential during some of these experiments, trying to begin looking at this parameter, which like pH, can have a more global effect on closed systems such as the apoplast. Phenolics such as APO that are induced upon bacterial ingress, seem likely to play a role in the plant bacterial interaction, but it will require additional and creative research to find and fully understand this role.

Oral tolerance:Recent advances on mechanisms and potential applications.

Oral tolerance is a type of immune hypo-responsiveness induced by oral administration of food or harmless gastrointestinal antigens. It is evident that the induction of oral tolerance can protect our body from enteric problems, such as food allergies and colitis caused by autoimmunity. Here we review the immunological mechanisms of oral tolerance, the role of T cell cytokines in generating tolerance and the impact of Peyer's patches and mesenteric lymph nodes, and discuss the part played by commensal microflora in the regulation and maintenance of the intestinal barrier. The potential clinical applications of oral tolerance in human disease therapy are also included in this review. Understanding the mechanisms of oral tolerance may lead to the development of alternative strategies for preventing or suppressing the symptoms of autoimmune diseases and allergies.

High salt diet ameliorates functional, electrophysiological and histological characteristics of murine spontaneous autoimmune polyneuropathy

BackgroundIt was previously reported that high salt dietary conditions can drive autoimmunity and worsen severity and symptoms of autoimmune diseases. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a common autoimmune condition of the peripheral nervous system which leads to progressive paralysis and sensory deficits due to a demyelination and secondary axonal loss of peripheral nerves. We used a previously described model with a knockout of CD86 in non-obese diabetic mice (CD86−/− NOD), which results in the spontaneous development of an autoimmune peripheral neuropathy similar to CIDP and investigated the influence of a high salt diet on functional impairment, electrophysiological parameters, demyelination and neuroinflammation in these mice. MethodsAt seven weeks of age, asymptomatic female CD86−/− NOD mice were randomly assigned to a normal or high salt diet containing 4% sodium chloride in food and 1% in water. The diet was continued for a total of 30 weeks. ResultsMice on the high salt diet showed a delayed onset of clinical symptoms and an ameliorated disease course with a reduced decline of locomotor function. Furthermore, electrophysiological parameters of neuropathy and demyelination were attenuated in mice on the high salt diet, which was confirmed with histological analysis. Additionally, we observed a reduced immune cell infiltration of sciatic nerves in mice which had received the high salt diet. ConclusionsWe demonstrate beneficial effects of high salt diet regarding disease progression, functional, electrophysiological and histological parameters in a transgenic mouse model of spontaneous autoimmune neuropathy.

171 - Redox- and bio-activity of Apocynin (acetovanillone) in plants, a plant phenolic that alleviates symptoms of autoimmune diseases in animals

Apocynin (APO), was shown to be the major constituent of and early herbal medicines used to reduce painful suffering from many ailments. Because of its proven utility in rat models, it is now an active candidate for treating humans for several major autoimmune diseases such as Alzheimer's, arthritis, and cardiovascular diseases. In plant research, APO is referred to as acetovanillone, a secondary metabolite that is induced in the leaf apoplast, the area outside the cell membrane, during bacterial invasion. In the medical research, it is considered to be a NADPH-oxidase inhibitor, blocking the production of ROS that causes the damage in autoimmunity. Since plants have a similar membrane bound NADPH oxidase activated during bacterial invasion, we wanted to explore whether APO might have similar properties in plants that have been found in animals. In addition, what effect APO might have on the redox environment since it is redox-active along with other apoplast phenolics.

Vitamin D and Immune Diseases in Children: A Mini-review

The purpose of this literature review was to summarize the knowledge about the effects of vitamin D on various autoimmune diseases. Research on the effects of vitamin D on the immune system increasingly shows that in cases of deficiency in vitamin D, adequate supplementing doses of this secosteroid, immunomodulatory hormone will enable us to prevent the onset or alleviate the symptoms of most autoimmune diseases. Conclusion – The importance of vitamin D’s influence on the immune system and the consequences of its deficiency will be the interest of future research and will finally reveal the importance of this vitamin in the pathophysiology of immune events.

The role of flavonoids in autoimmune diseases: Therapeutic updates.

Flavonoids are natural polyphenolic compounds which are included in a panoply of drugs and used to treat and/or manage human ailments such as metabolic, cardiovascular, neurological disorders and cancer. Thus, the purpose of this review is to emphasize the importance of flavonoids for the treatment of autoimmune diseases and put into the limelight of the scientific community several health-promoting effects of flavonoids which could be beneficial for the development of novel drugs from natural products. Despite available reviews on flavonoids targeting various disease conditions, a comprehensive review of flavonoids for autoimmune diseases is still lacking. To the best of our knowledge, this is the first attempt to review the potential of flavonoids for autoimmune diseases. The structure-activity relationship of flavonoids in this review revealed that the rearrangement and introduction of other functional groups into the basic skeleton of flavonoids might lead to the development of new drugs which will be helpful in relieving the painful symptoms of various autoimmune diseases.

Audiovestibular Symptoms in Systemic Autoimmune Diseases.

Immune-mediated inner ear disease can be primary, when the autoimmune response is against the inner ear, or secondary. The latter is characterized by the involvement of the ear in the presence of systemic autoimmune conditions. Sensorineural hearing loss is the most common audiovestibular symptom associated with systemic autoimmune diseases, although conductive hearing impairment may also be present. Hearing loss may present in a sudden, slowly, rapidly progressive or fluctuating form, and is mostly bilateral and asymmetric. Hearing loss shows a good response to corticosteroid therapy that may lead to near-complete hearing restoration. Vestibular symptoms, tinnitus, and aural fullness can be found in patients with systemic autoimmune diseases; they often mimic primary inner ear disorders such as Menière's disease and mainly affect both ears simultaneously. Awareness of inner ear involvement in systemic autoimmune diseases is essential for the good response shown to appropriate treatment. However, it is often misdiagnosed due to variable clinical presentation, limited knowledge, sparse evidence, and lack of specific diagnostic tests. The aim of this review is to analyse available evidence, often only reported in the form of case reports due to the rarity of some of these conditions, of the different clinical presentations of audiological and vestibular symptoms in systemic autoimmune diseases.

High prevalence of a variety of autoantibodies in a population of hepatitis C virus-infected individuals.

Hepatitis C virus (HCV) infection has been related to self-reactivity, extrahepatic manifestations and autoimmune diseases. The main goals of this work were to study the prevalence of autoantibodies and their relationship with viral titers and biochemical markers of hepatic damage in patients infected with HCV. Autoantibodies (ANA, AMA, SMA, APC, LKM, DNAds, ANCA, ATG and RF) were determined in 73 individuals with chronic HCV infection and 44 healthy volunteers. The presence of these antibodies was related to demographic variables, viral titers and biochemical parameters. A high prevalence of autoantibodies, particularly for RF, that was associated with female gender was observed in HCV-infected patients. In addition, SMA, ANA and ATG showed increased frequencies in HCV infection. Interestingly, the concurrent detection of SMA and more than one autoantibody was associated with high gGT levels. Notably, concurrent higher gGT, HCV and SMA levels were observed in male patients as compared to their female counterparts. These results indicate a relationship between HCV infection and the concurrent detection of various autoantibodies in the absence of symptoms of autoimmune diseases. They also suggest a link among the presence of a variety of autoantibodies simultaneously with SMA, increased gGT levels and HCV titers in a population of male patients.

Safety of Programmed Death-1 Pathway Inhibitors Among Patients With Non-Small-Cell Lung Cancer and Preexisting Autoimmune Disorders.

Purpose Although programmed death (PD)-1 pathway inhibitors are now used in nearly all patients with advanced non-small-cell lung cancer (NSCLC), the large number of patients with NSCLC and concurrent autoimmune disease (AID) have been universally excluded from immunotherapy clinical trials. Therefore, the safety of PD-1 and PD-ligand 1 (PD-L1) inhibitors in patients with NSCLC and underlying AID is currently unknown. Methods As part of a multi-institutional effort, we retrospectively collected clinicopathologic data from patients with NSCLC and a history of AID who received monotherapy with either a PD-1 or a PD-L1 (herein referred to as PD-[L]1) inhibitor. Qualifying AIDs included but were not limited to: rheumatologic, neurologic, endocrine, GI, and dermatologic conditions. Results We identified 56 patients with NSCLC and an AID who received a PD-(L)1 inhibitor. At the time of treatment initiation, 18% of patients had active AID symptoms and 20% were receiving immunomodulatory agents for their AID. A total of 55% of patients developed an AID flare and/or an immune-related adverse event (irAE). Exacerbation of the AID occurred in 13 patients (23% of the whole cohort), four of whom required systemic corticosteroids. Immune-related adverse events occurred in 21 patients (38%). Among irAEs, 74% were grade 1 or 2 and 26% were grade 3 or 4; eight patients required corticosteroids for irAE management. PD-(L)1 therapy was permanently discontinued in eight patients (14%) because of irAEs. The overall response rate to immunotherapy in this population was 22%. Conclusion In patients with NSCLC with AID treated with a PD-(L)1 inhibitor, exacerbation of AID occurred in a minority of patients. The incidence of irAEs was similar to reported rates in clinical trials where patients with AID were excluded. Adverse events were generally manageable and infrequently led to permanent discontinuation of immunotherapy.

Abstract P238: Remission/Cure of Autoimmune Diseases by a Lectin Limite Diet Supplemented With Probiotics, Prebiotics, and Polyphenols

All autoimmune diseases are highly associated with increased rates of coronary artery and vascular disease secondary to immune cell attack on epithelial cells. The causes of autoimmune disease (AID) seem to be multifactorial. However, the idea that derangement of the microbiome, breaches of the intestinal barrier (leaky gut) and introduction into the human diet of plant defense molecules such as lectins, which are capable of molecular mimicry, prompted our group to investigate the application of a lectin limited diet, coupled with probiotics and prebiotics (The Pant Paradox Protocol) to impact biomarker proven autoimmune disease activity in humans and their impact on endothelial biomarkers of inflammation. One hundred and two consecutive patients with immunoassay markers of autoimmune disease activity, i.e., RF, anti-CCP, ANA, Histone, etc, and signs and symptoms of RA, Lupus, Sjogrens, Crohns, Colitis, Scleroderma, Mixed Connective Tissue Disease, and biomarkers of endothelial inflammation, were enrolled into a program of elimination of major dietary lectins, consisting of all grains and pseudo grains, beans and legumes, peanuts, cashews, nightshades, squashes, and Casein A1 milk products (The Plant Paradox Program), supplemented with probiotics and prebiotics including resistant starches and polyphenol supplements. All pts initially low Vit D levels and low Omega 3 index and adiponectin levels above 16mg/dl. Biomarkers of inflammation, hs-CRP, TNF-alpha, IL-6, fibrinogen, myeloperoxidase and autoimmune markers were measured every 3 months. 95/102 patients achieved complete resolution of autoimmune markers and inflammatory markers within 9 months. The other 7/102 patients all had reduced markers, but incomplete resolution. 80/102 patients were weaned from all immunosuppressive and/or biologic medications without rebound. We conclude that a lectin limited diet, supplemented with pro and prebiotics, and polyphenols are capable of curing or putting into remission most autoimmune diseases.

The Effects of Dendritic Cell Hypersensitivity on Persistent Viral Infection.

Caspase-8 (CASP8) is known as an executioner of apoptosis, but more recent studies have shown that it participates in the regulation of necroptosis and innate immunity. In this study, we show that CASP8 negatively regulates retinoic acid-inducible gene I (RIG-I) signaling such that, in its absence, stimulation of the RIG-I pathway in dendritic cells (DCs) produced modestly enhanced activation of IFN regulatory factor 3 with correspondingly greater amounts of proinflammatory cytokines. In addition, mice lacking DC-specific CASP8 (dcCasp8-/- mice) develop age-dependent symptoms of autoimmune disease characterized by hyperactive DCs and T cells, spleen and liver immunopathology, and the appearance of Th1-polarized CD4+ T cells. Such mice infected with chronic lymphocytic choriomeningitis virus, an RNA virus detected by RIG-I, mounted an enhanced lymphocytic choriomeningitis virus-specific immune response as measured by increased proportions of Ag-specific CD4+ T cells and multicytokine-producing CD4+ and CD8+ T cells. These results show that CASP8 subtly modulates DC maturation, which controls the spontaneous appearance of autoimmune T cells while simultaneously attenuating the acquired immune system and its potential to control a persistent viral infection.