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ID PMID Title PublicationDate abstract
33093895 Influence of a combination of triptolide and ferulic acid on the activities of CYP450 enzy 2020 Dec Topical administration of triptolide (TP) is effective in the treatment of rheumatoid arthritis (RA), but it can also induce skin irritation. Previous studies have used data mining strategies to analyze the application of Tripterygium wilfordii in the treatment of RA and have shown that TP and ferulic acid (FA) can be used in combination due to their component compatibility. The aims of the present study were to investigate the mechanisms underlying the effects of TP treatment and to identify its effects on metabolism and oxidative damage in the skin. MTT assay results suggested that the HaCaT cell survival rate was significantly increased when the compatibility ratio of TP to FA was 1:100. Moreover, the combination of TP with FA (TP + FA) did not significantly affect the activities of the cytochrome P40 (CYP) enzymes CYP family 1 subfamily A member 2 (CYP1A2), CYP2E1 and CYP3A4, when used as a 'cocktail'. It was found that TP + FA significantly decreased the production levels of reactive oxygen species (ROS), superoxide dismutase and malondialdehyde in HaCaT cells, while significantly increasing levels of glutathione and catalase. In addition, TP + FA significantly increased nuclear factor erythroid 2-related factor 2 protein expression, compared with TP alone. Thus, the present results indicated that the underlying mechanism of TP + FA efficacy may be related to decreased ROS production level in HaCaT cells, increased production levels of key antioxidant factors and increased antioxidant activity of the epidermis, all of which were correlated with a protective effect against oxidative damage.
32849515 The AHR Signaling Attenuates Autoimmune Responses During the Development of Type 1 Diabete 2020 The aryl hydrocarbon receptor (AHR) is a ligand-activated transcriptional factor widely expressed in immune cells. Its ligands range from xenobiotics and natural substances to metabolites, which renders it capable of sensing and responding to a variety of environmental cues. Although AHR signaling has long been recognized to be implicated in the pathogenesis of autoimmune disorders, such as rheumatoid arthritis (RA), colitis, and systemic lupus erythematosus (SLE), its effect on the pathogenesis of type 1 diabetes (T1D) remains less understood. In this review, we intend to summarize its potential implication in T1D pathogenesis and to sort out the related regulatory mechanisms in different types of immune cells. Emerging evidence supports that β cell destruction caused by autoimmune responses can be rectified by AHR signaling. Upon activation by its ligands, AHR not only modulates the development and functionality of immune cells, but also suppresses the expression of inflammatory cytokines, through which AHR attenuates autoimmune responses during the course of T1D development. Since AHR-initiated biological effects vary between different types of ligands, additional studies would be necessary to characterize or de novo synthesize effective and safe ligands aimed to replenish our arsenal in fighting autoimmune responses and β mass loss in a T1D setting.
32810557 A comprehensive review on miR-146a molecular mechanisms in a wide spectrum of immune and n 2020 Nov MicroRNAs (miRNAs) are single-strand endogenous and non-coding RNA molecules with a length of about 22 nucleotides, which regulate genes expression, through modulating the translation and stability of their target mRNAs. miR-146a is one of the most studied miRNAs, due to its central role in immune system homeostasis and control of the innate and acquired immune responses. Accordingly, abnormal expression or function of miR-146a results in the incidence and progression of immune and non-immune inflammatory diseases. Its deregulated expression pattern and inefficient function have been reported in a wide spectrum of these illnesses. Based on the existing evidence, this miRNA qualifies as an ideal biomarker for diagnosis, prognosis, and activity evaluation of immune and non-immune inflammatory disorders. Moreover, much attention has recently been paid to therapeutic potential of miR-146a and several researchers have assessed the effects of different drugs on expression and function of this miRNA at diverse experimental, animal, besides human levels, reporting motivating results in the treatment of the diseases. Here, in this comprehensive review, we provide an overview of miR-146a role in the pathogenesis and progression of several immune and non-immune inflammatory diseases such as Rheumatoid arthritis, Systemic lupus erythematosus, Inflammatory bowel disease, Multiple sclerosis, Psoriasis, Graves' disease, Atherosclerosis, Hepatitis, Chronic obstructive pulmonary disease, etc., discuss about its eligibility for being a desirable biomarker for these disorders, and also highlight its therapeutic potential. Understanding these mechanisms underlies the selecting and designing the proper therapeutic targets and medications, which eventually facilitate the treatment process.
32785936 Management of cardiac arrhythmias in patients with autoimmune disease-Insights from EHRA Y 2020 Oct BACKGROUND: Since arrhythmia treatment in patients with autoimmune disease (AD) is challenging, we aimed to assess the common "real-world" practice in the electrophysiology centers. METHODS: Twenty-four young electrophysiologists being part of European Heart Rhythm Association filled questionnaire regarding arrhythmia management in AD. RESULTS: Rheumatoid arthritis was the most commonly reported AD accompanied by cardiac arrhythmias. The most frequent observed arrhythmias were atrial fibrillation and premature atrial/ventricular contractions. Most often electrocardiographic abnormalities observed were increased heart rate variability, QT interval prolongation, and P-wave dispersion, whereas echocardiographic abnormalities included left atrial enlargement, pericardial infusion, and left ventricular dysfunction. The most useful tool for arrhythmia management was guidelines and evidence-based medicine, while training courses and websites were at least useful. A close collaboration with other specialists in arrhythmia management was reported in 58.3% of respondents. Glucocorticoids and cytostatic were the most reported arrhythmia-induced drugs, whereas amiodarone and beta-blockers were most effective antiarrhythmic drugs. The main reason that discouraged respondents from cardiac implantable devices implantation and catheter ablation was high infection complications risk and recurrences during long-term follow-up, respectively. CONCLUSIONS: Scant data and guidelines enforce exchange of experience to improve the arrhythmia treatment in AD.
32772198 Intrafamilial phenotypic distinction of hypophosphatasia with identical tissue nonspecific 2020 Nov Hypophosphatasia (HPP) is caused by mutations in the tissue nonspecific alkaline phosphatase (TNSALP) gene in an autosomal recessive or dominant manner and characterized by defective mineralization of bone and low serum ALP levels. In this report, we present a family with HPP mother (case 1) and HPP child (case 2) who have identical TNSALP gene mutation (c.1015G>A p.Gly339Arg heterozygous mutation) but distinct clinical phenotypes. Whereas case 1 appeared to be asymptomatic despite extremely low levels of serum ALP, case 2 had several HPP-related symptoms, such as tooth loss, fractures, short stature, with slightly decreased ALP levels. Upon the diagnosis of HPP, case 1 discontinued denosumab, which was used to treat her rheumatoid arthritis, concerning the risk of atypical femoral fractures. The clinical course of this family was suggestive in a genotype-phenotype imbalance in HPP, the underdiagnosis of HPP in adults, and the risk of atypical femoral fractures using bone resorption inhibitors.
32622513 The roles of PPARγ and its agonists in autoimmune diseases: A comprehensive review. 2020 Sep Autoimmune diseases are common diseases of the immune system that are characterized by the loss of self-tolerance and the production of autoantibodies; the breakdown of immune tolerance and the prolonged inflammatory reaction are undisputedly core steps in the initiation and maintenance of autoimmunity. Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that belong to the nuclear hormone receptor family and act as ligand-activated transcription factors. There are three different isotypes of PPARs: PPARα, PPARγ, and PPARβ/δ. PPARγ is an established regulator of glucose homeostasis and lipid metabolism. Recent studies have demonstrated that PPARγ exhibits anti-inflammatory and anti-fibrotic effects in multiple disease models. PPARγ can also modulate the activation and polarization of macrophages, regulate the function of dendritic cells and mediate T cell survival, activation, and differentiation. In this review, we summarize the signaling pathways and biological functions of PPARγ and focus on how PPARγ and its agonists play protective roles in autoimmune diseases, including autoimmune thyroid diseases, multiple sclerosis, rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, primary Sjogren syndrome and primary biliary cirrhosis.
32616337 Decreased levels of interleukin 27 in the serum of vitiligo patients. 2020 Sep BACKGROUND: Vitiligo is a common skin disorder in which melanocytes are destroyed by auto-reactive immune responses. The loss of melanocytes results in the appearance of depigmented areas in different parts of the body. Cytokines have remarkable roles in the pathogenesis of vitiligo, such as IL-1, IL-6, and TNF-α; interleukin 27 (IL-27) is a new member of the IL-6/IL-12 family, mainly released by activated antigen-presenting cells. IL-27 has been suggested to function as a pro-inflammatory as well as an anti-inflammatory cytokine. Altered concentrations of IL-27 have been shown in various auto-immune diseases such as multiple sclerosis, rheumatoid arthritis, and psoriasis. No studies have been conducted to determine the expression of this cytokine in vitiligo patients. OBJECTIVE: The objective of this study was to determine the serum concentration of IL-27 in vitiligo patients and compare it with normal individuals. METHODS: The serum concentration of IL-27 in 79 vitiligo patients was evaluated in comparison to 45 healthy controls using ELISA assay. RESULTS: Results showed decreased concentration of IL-27 in vitiligo patients as compared with healthy subjects (p=0.026). Furthermore, no correlation between IL-27 concentrations and disease parameters such as vitiligo severity and the extension of the depigmented area was observed. STUDY LIMITATION: A larger sample size would be more recommended for this study. CONCLUSION: The reduction in the serum levels of IL-27 in vitiligo patients compared to normal subjects suggested the possible anti-inflammatory role of this cytokine in vitiligo. Thus, IL-27 may be considered as a new target for the manipulation of the immune system in vitiligo patients.
32579188 Role of bioactive sphingolipids in physiology and pathology. 2020 Sep 23 Sphingolipids are a class of complex lipids containing a backbone of sphingoid bases, namely the organic aliphatic amino alcohol sphingosine (Sph), that are essential constituents of eukaryotic cells. They were first described as major components of cell membrane architecture, but it is now well established that some sphingolipids are bioactive and can regulate key biological functions. These include cell growth and survival, cell differentiation, angiogenesis, autophagy, cell migration, or organogenesis. Furthermore, some bioactive sphingolipids are implicated in pathological processes including inflammation-associated illnesses such as atherosclerosis, rheumatoid arthritis, inflammatory bowel disease (namely Crohn's disease and ulcerative colitis), type II diabetes, obesity, and cancer. A major sphingolipid metabolite is ceramide, which is the core of sphingolipid metabolism and can act as second messenger, especially when it is produced at the plasma membrane of cells. Ceramides promote cell cycle arrest and apoptosis. However, ceramide 1-phosphate (C1P), the product of ceramide kinase (CerK), and Sph 1-phosphate (S1P), which is generated by the action of Sph kinases (SphK), stimulate cell proliferation and inhibit apoptosis. Recently, C1P has been implicated in the spontaneous migration of cells from some types of cancer, and can enhance cell migration/invasion of malignant cells through interaction with a Gi protein-coupled receptor. In addition, CerK and SphK are implicated in inflammatory responses, some of which are associated with cancer progression and metastasis. Hence, targeting these sphingolipid kinases to inhibit C1P or S1P production, or blockade of their receptors might contribute to the development of novel therapeutic strategies to reduce metabolic alterations and disease.
32564041 Implementation and analysis of Babesia immunoassay testing. 2020 Jun 17 Lifelong withdrawal from the donor population of those who have been diagnosed with babesiosis must be used for transmission prevention. AIM: The aim of the study was a detection of Babesia antibodies level with the usage of experimental Babesia divergens whole-cell slide antigen and commercial B. microti immunofluorescence assay substrate slide (Fuller Laboratories, USA). MATERIALS AND METHODS: Experimental B. divergens whole-cell slide antigen in addition to commercial B. microti IFA substrate slide was used to create a diagnostic kit for serum Babesia antibodies level detecting, as well as for a babesiosis serodiagnosis clinical trial of different origins blood samples (patients with Lyme disease, rheumatoid arthritis and toxoplasmosis; human blood donors; cattle). RESULTS: Antibodies to B. divergens (5.4%) and B. microti (2.3%) were detected with higher (p <0.05) frequency at Lyme disease patients (16.7%) than at blood donors (1.7%). Diagnostically significant IgG titres (= 1:128) were found in 13.3% of blood samples from Lyme disease patients and 1.7% from blood donors. Specific IgM were also found in 13.3% blood samples from Lyme disease patients. Among blood samples from Lyme disease patients, in which diagnostically significant titres of Babesia antibodies were detected (16.7%), 60% of them were represented by IgG and IgM (rA= 0.63), and in 40% only one of them reached diagnostically significant titre. Conclusions. Advantages of babesiosis IFA diagnostics. CONCLUSIONS: Advantages of babesiosis IFA diagnostics are combined with its significant disadvantages (principle of evaluation, low sensitivity in the initial period of the disease, probability of false positives, absence of validated test systems and research protocols for B. divergens and B. divergens-like species).
32562158 Disorders of the Aorta and Aortic Valve in Connective Tissue Diseases. 2020 Jun 19 PURPOSE OF REVIEW: The incidence of aortic valve disease in inherited connective tissue disorders is well documented; however, recent studies have only begun to unravel the pathology behind this association. In this review, we aim to describe the etiology, clinical manifestations, management, and prognosis of aortic and aortic valvular disorders that co-exist in a variety of connective tissue diseases. An extensive literature review was performed in PubMed. Articles from 2008 to 2018 were included for review. Predetermined search terms used in PubMed include "aortic manifestation of connective tissue diseases" and "aortic valve disorders in rheumatologic disease." RECENT FINDINGS: Manifestations of aortic valve disease in the context of connective tissue disorders include valvular stenosis, regurgitation, and/or thoracic aortic aneurysms. Both inherited and inflammatory connective tissue disorders contribute to aortic valve damage with increased susceptibility associated with specific gene variants. Anti-inflammatory and immunosuppressive therapies have demonstrated beneficial results in Marfan's syndrome, Behcet disease, rheumatoid arthritis, ankylosing spondylitis, and systemic sclerosis, often leading to remission. Yet, such therapy is less effective in other disorders compared to alternative treatments such as surgical intervention. Additionally, regular echocardiographic studies should be recommended to those suffering from these disorders, especially those at higher risk for cardiovascular involvement. Given the rates of relapse with immunosuppressants, even following aortic valve replacement, further studies are needed to determine if certain dosing and/or combinations of immunosuppressants could be given to those diagnosed with connective tissue diseases to prevent progression of aortic valve involvement.
32372426 miR-506-3p alleviates uncontrolled osteoclastogenesis via repression of RANKL/NFATc1 signa 2020 Dec Bone erosion is the major cause of deformities in autoimmune disease conditions such as osteoporosis and rheumatoid arthritis. Aberrant receptor activator of nuclear factor kappa B ligand (RANKL) secretion in bone disorders have been implicated to promote uncontrolled osteoclast differentiation through the regulation of nuclear factor of activated T cells 1 (NFATc1) transcription factor. This phenomenon is governed by several molecular factors including microRNAs, which are under-expressed during disease progression. This report focuses on elucidating the molecular mechanism of miR-506-3p towards the RANKL/NFATc1 pathway. miR-506-3p showed high binding affinity towards NFATc1 (ΔG = -22.4 kcal/mol). Bone marrow-derived macrophages (BMMs) isolated from rats stimulated with RANKL (100 ng/ml) showed active expression of NFATc1 which differentiated into mature osteoclasts. Moreover, NFATc1 activation resulted in downstream secretion of various bone resorptive enzymes (cathepsin K, carbonic anhydrase II, tartarate acid phosphatase, and matrix metalloproteinase 9) which lead to active bone resorption. However, transfection of miR-506-3p resulted in selective repression of NFATc1 inside the cells. This further resulted in the diminished release of bone resorptive enzymes that were essential for the degradation of the bone. Overall, we predict that miR-506-3p can be used as a molecular intervention for RANKL/NFATc1 mediated osteoclastogenesis.
32157914 Recovery of activity level following total hip arthroplasty in patients less than 60 yea 2021 Sep BACKGROUND: Total hip arthroplasty (THA) is a useful treatment for pain relief and functional improvement. THA indications now include younger, more active patients, with improved implant design and bearing materials. We aimed to investigate daily activity level and return to work after THA, about which limited information is available. Moreover, differences in patient background and clinical parameters including size of femoral head and surgical approach were evaluated. METHODS: A multicentre survey was carried out in patients below 60 years, undergoing THA between 2007 and 2012, at least 1 year after surgery. Primary THA patients with osteoarthritis, avascular necrosis, rheumatoid arthritis, hip dysplasia, and no history of postoperative complications were included. The questionnaire included daily activity and occupation levels before and after surgery. University of California, Los Angeles (UCLA) activity score and occupational classification index were defined, and statistical analysis was performed. RESULTS: The mean preoperative UCLA score in 204 patients was 4.55 which improved to 6.17 after surgery. Pre- as well as postoperative UCLA scores in males were significantly higher than that in females. No differences were observed in other parameters. Return to work rate in males was 94.4%; significantly higher than that in females (52.3%). Younger patients with large head THA were more likely to return to work. CONCLUSIONS: Most patients showed improved activity levels. Satisfaction levels were higher in young males with large femoral head size. Patients with a higher preoperative work level are expected to have a higher return to work rate.
32149199 Phenolic profile and anti-inflammatory activity of four Moroccan date (Phoenix dactylifera 2020 Feb Date (Phoenix dactylifera L.) seeds are seen as good drug to cure rheumatoid arthritis and asthma in Moroccan traditional medicine. The present research aimed to study the anti-inflammatory effect, of methanol extract of different date seed varieties using membrane stabilizing effect, nitric oxide radical scavenging activity, inhibition of protein denaturation, carrageenan-induced paw edema and croton oil induced ear edema. The polyphenolic profile was examined using HPLC-DAD. Rutin, quercetin, p-coumaric and caffeic acids were the main among the analysed phenolic compounds. Concerning the anti-inflammatory activity, the analysed date seed were significantly effective in scavenging nitric oxide free radical, in stabilisation of erythrocyte membrane and possessed a high anti denaturation effect. In agreement with this finding, date seed exhibited a profound ability to reduce paw and ear swelling induced by carrageenan and croton oil respectively. The biochemical parameters showed that date seed are able to reduce the erythrocyte sedimentation rate (ERS) and C-reactive protein (CRP) concentration in rats used in Carrageenan-induced paw edema model. The predominant phenolic compounds are the potential candidates that drive these activities and the differences observed among varieties are related to their chemical composition. These data suggest that date seeds can be explored as a therapeutic agent for the treatment of inflammatory diseases.
32039889 An unexpected co-crystal structure of the calpain PEF(S) domain with Hfq reveals a potenti 2020 Feb 1 Calpain is a Ca(2+)-activated, heterodimeric cysteine protease consisting of a large catalytic subunit and a small regulatory subunit. Dysregulation of this enzyme is involved in a range of pathological conditions such as cancer, Alzheimer's disease and rheumatoid arthritis, and thus calpain I is a drug target with potential therapeutic applications. Difficulty in the production of this enzyme has hindered structural and functional investigations in the past, although heterodimeric calpain I can be generated by Escherichia coli expression in low yield. Here, an unexpected structure discovered during crystallization trials of heterodimeric calpain I (CAPN1C115S + CAPNS1ΔGR) is reported. A novel co-crystal structure of the PEF(S) domain from the dissociated regulatory small subunit of calpain I and the RNA-binding chaperone Hfq, which was likely to be overproduced as a stress response to the recombinant expression conditions, was obtained, providing unexpected insight in the chaperone function of Hfq.
32026881 Acquired hemophilia. 2020 Acquired hemophilia (AH) is an autoimmune hemostatic disorder mediated by autoantibodies directed against factor VIII: C. In 52% of cases, the cause is unknown or is not associated with other pathological entities; in the rest, there are concomitant factors: lupus, rheumatoid arthritis, cancer, pregnancy, and medications. In Mexico, there is not a registry of AH, and awareness of the disease among health personnel is low. The groups with the highest incidence are women of childbearing age and individuals older than 70 years. It is characterized by severe bleeding, especially after trauma and normal childbirth or cesarean delivery, and large ecchymoses in the trunk and extremities. The suspicion is simple, it just takes for sudden, severe hemorrhage and a prolonged activated partial thromboplastin time that is not corrected with plasma to concur in an individual. Treatment involves achieving hemostasis and eradicating the antibody. The former is achieved with recombinant activated factor VII or activated prothrombin complex concentrate. Cyclophosphamide, prednisone or rituximab are used to eradicate the antibody. Most cases of AH are not diagnosed, which translates into a high mortality rate. Given that awareness about the disease among physicians is low, it is not suspected, neither diagnosed, and nor is it treated. This document reviews the most recent data on AH and expands on its diagnosis and treatment.
31998982 Validated LC-MS/MS method for quantitation of a selective JAK1 inhibitor, filgotinib in ra 2020 Apr Filgotinib is a selective JAK1 (Janus kinase) inhibitor, filed in Japan for the treatment of rheumatoid arthritis. In this paper, we report a validated liquid chromatography coupled with tandem mass spectrometry for the quantification of filgotinib in rat plasma using tofacitinib as an internal standard (IS) as per the Food and Drug Administration regulatory guidelines. Filgotinib and the IS were extracted from rat plasma using ethyl acetate as an extraction solvent and chromatographed using an isocratic mobile phase (0.2% formic acid:acetonitrile; 20:80, v/v) at a flow rate of 0.9 mL/min on a Gemini C(18) column. Filgotinib and the IS were eluted at ~1.31 and 0.89 min, respectively. The MS/MS ion transitions monitored were m/z 426.3 → 291.3 and m/z 313.2 → 149.2 for filgotinib and the IS, respectively. The calibration range was 0.78-1924 ng/mL. No matrix effect and carryover were observed. Intra- and inter-day accuracies and precisions were within the acceptance range. Filgotinib was stable for three freeze-thaw cycles: on bench-top up to 6 h, in an autosampler up to 21 h, and at -80°C for 1 month. This novel method has been applied to a pharmacokinetic study in rats.
31992476 A panoramic review of IL-6: Structure, pathophysiological roles and inhibitors. 2020 Mar 1 Interleukin-6 (IL-6) is a pleiotropic pro-inflammatory cytokine. Its deregulation is associated with chronic inflammation, and multifactorial auto-immune disorders. It mediates its biological roles through a hexameric complex composed of IL-6 itself, its receptor IL-6R, and glycoprotein 130 (IL-6/IL-6R/gp130). This complex, in turn, activates different signaling mechanisms (classical and trans-signaling) to execute various biochemical functions. The trans-signaling mechanism activates various pathological routes, like JAK/STAT3, Ras/MAPK, PI3K-PKB/Akt, and regulation of CD4+ T cells and VEGF levels, which cause cancer, multiple sclerosis, rheumatoid arthritis, anemia, inflammatory bowel disease, Crohn's disease, and Alzheimer's disease. Involvement of IL-6 in pathophysiology of these complex diseases makes it an important target for the treatment of these diseases. Though some anti-IL-6 monoclonal antibodies are being used clinically, but their high cost, only parenteral administration, and possibility of immunogenicity have limited their use, and warranted the development of novel small non-peptide molecules as IL-6 inhibitors. In the present report, all molecules reported in literature as IL-6 inhibitors have been classified as IL-6 production, IL-6R, and IL-6 signaling inhibitors. Reports available till date are critically studied to identify important and salient structural features common in these molecules. These analyses would assist medicinal chemists to design novel and potent IL-6 production and signaling inhibitors, through knowledge- and/or computer-based approaches, for the treatment of complex multifactorial diseases.
31883831 Innate immunity as the trigger of systemic autoimmune diseases. 2020 Jun The innate immune system consists of a variety of elements controlling and participating in virtually all aspects of inflammation and immunity. It is crucial for host defense, but on the other hand its improper activation is also thought to be responsible for the generation of autoimmunity and therefore diseases such as autoimmune arthritides like rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS) or inflammatory bowel disease. The innate immune system stands both at the beginning as well as the end of autoimmunity. On one hand, it regulates the activation of the adaptive immune system and the breach of self-tolerance, as antigen presenting cells (APCs), especially dendritic cells, are essential for the activation of naïve antigen specific T cells, a crucial step in the development of autoimmunity. Various factors controlling the function of dendritic cells have been identified that directly regulate lymphocyte homeostasis and in some instances the generation of organ specific autoimmunity. Moreover, microbial cues have been identified that are prerequisites for the generation of several specific autoimmune diseases. On the other hand, the innate immune system is also responsible for mediating the resulting organ damage underlying the clinical symptoms of a given autoimmune disease via production of proinflammatory cytokines that amplify local inflammation and further activate other immune or parenchymal cells in the vicinity, the generation of matrix degrading and proteolytic enzymes or reactive oxygen species directly causing tissue damage. In the last decades, molecular characterization of cell types and their subsets as well as both positive and negative regulators of immunity has led to the generation of various scenarios of how autoimmunity develops, which eventually might lead to the development of targeted interventions for autoimmune diseases. In this review, we try to summarize the elements that are contributing to the initiation and perpetuation of autoimmune responses.
31841960 Micronutrients in autoimmune diseases: possible therapeutic benefits of zinc and vitamin D 2020 Mar A functional immune system is essential for healthy life. This is achieved by the coordinate activation and interaction of different immune cells. One should be aware that activation of the immune response is as important as its deactivation when the pathogens are cleared, as otherwise host tissue can be damaged up to life-threatening levels. Autoimmune diseases (AID) represent a phenomenon of immune cells attacking host cells and tissue. Five to eight percent of the world's population are currently affected by 80-100 AID. In recent years, the incidence has been constantly increasing, reaching alarmingly high numbers particularly for type 1 diabetes mellitus, Crohn's disease, rheumatoid arthritis, Sjogren's syndrome and multiple sclerosis. This indicates a higher societal burden of AID for the future. This article provides an overview of general concepts of triggers and underlying mechanisms leading to self-destruction. Lately, several original concepts of disease etiology were revised, and there is a variety of hypotheses on triggers, underlying mechanisms and preventive actions. This article concentrates on the importance of nutrition, especially zinc and vitamin D, for balancing the immune function. Homespun nutritional remedies seem to reenter today's therapeutic strategies. Current treatment approaches are largely symptomatic or suppress the immune system. However, recent studies reveal significant benefits of nutrition-related therapeutic approaches including prevention and treatment of established disease, which offer a cost-efficient and trigger-unspecific alternative addressing balancing rather than suppression of the immune system. Zinc and vitamin D are currently the best studied and most promising candidates for therapeutic intervention.
31498065 Effects of birth months on rheumatic diseases in South Korea: a nationwide case-control st 2020 May OBJECTIVES: Birth month/season impacts the development of certain diseases. However, the effect of birth month/season on the development of rheumatic diseases has not been thoroughly investigated. Thus, the objective of this study was to determine whether birth month/season might affect the development of rheumatic diseases. METHODS: Birth month patterns of patients with various rheumatic diseases were compared with those of the general population. The dataset included 17,247,458 individuals from the health insurance review and assessment service database of Korea. RESULTS: Among 24 rheumatic diseases, the development of Crohn's disease, ulcerative colitis (UC), rheumatoid arthritis, Sjögren's syndrome, polymyalgia rheumatica, ankylosing spondylitis (AS), gout, and fibromyalgia (FM) was significantly associated with birth month/season. UC and AS were more prevalent in individuals born in February/winter. On the contrary, those who were born in June or July/summer were at a higher risk of gout and FM. CONCLUSIONS: Seasonal variations in infectious agents, sun exposure, and food ingestion during gestation or early infancy seem to explain the association between birth month/season and development of rheumatic diseases.