Abstract：
:The pathophysiology of autoimmune diseases such as Multiple Sclerosis (MS) involves a complex interaction between genetic and environmental factors. Studies of monozygotic twins suggest a significant role for environmental factors in susceptibility to MS. Numerous studies, driven by the "Hygiene Hypothesis," have focused on the role of environmental factors in allergic and autoimmune diseases. The hygiene hypothesis postulates that individuals living in environments that are too "clean" lack the requisite exposure to "immune-tolerizing" microbial products, resulting in poorly regulated immune systems and increased immune-mediated diseases. Interestingly, few studies have linked MS with the hygiene hypothesis. Similarly, although numerous studies have examined the role of the microbiome in autoimmune diseases, there has been no consistent documentation of disease-specific alterations in the MS microbiome. In this review, we present evidence that integrating the hygiene hypothesis and the microbiome allows for the identification of novel pathophysiologic mechanisms in MS. Our central hypothesis is that the microbiome in MS represents a "defective environment" that fails to provide normal levels of "TLR2-tolerizing" bacterial products to the systemic immune system. Consistent with the hygiene hypothesis, we posit that this defective microbiome function results in abnormally regulated systemic innate immune TLR2 responses that play a critical role in both the inflammatory and defective remyelinative aspects of MS. We have completed proof of concept studies that support the inflammatory, remyelinating, and human immune response components of this paradigm. Our studies suggest that induction of TLR2 tolerance may represent a novel approach to treating MS, inhibiting autoimmune inflammation while simultaneously facilitating remyelination.
journal_name
Autoimmun Revjournal_title
Autoimmunity reviewsauthors
Wasko NJ,Nichols F,Clark RBdoi
10.1016/j.autrev.2019.102430subject
Has Abstractpub_date
2020-01-01 00:00:00pages
102430issue
1eissn
1568-9972issn
1873-0183pii
S1568-9972(19)30240-Xjournal_volume
19pub_type
杂志文章,评审abstract：:In Multiple Sclerosis (MS) patients, conventional magnetic resonance imaging (MRI) shows a pattern of white matter (WM) disruption but may also overlook some WM damage. Diffusion tensor MRI (DT-MRI) can provide important in-vivo information about fiber direction that is not provided by conventional MRI. The geometry o...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2006.06.003
更新日期：2006-10-01 00:00:00
abstract：:Posterior reversible encephalopathy syndrome is a rare clinicoradiological entity characterized by typical MRI findings located in the occipital and parietal lobes, caused by subcortical vasogenic edema. It was first described as a distinctive syndrome by Hinchey in 1996. Etiopathogenesis is not clear, although it is ...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2015.05.006
更新日期：2015-09-01 00:00:00
abstract：:Primary biliary cirrhosis (PBC) has been coined a model autoimmune disease. In fact, it does share many similarities with other autoimmune diseases, but there are striking differences that illustrate the uniqueness of the immunopathology. Firstly, similar to other autoimmune diseases, there is an intense humoral and c...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2004.04.001
更新日期：2004-06-01 00:00:00
abstract：:Coexisting morbidities in CVID include bronchiectasis, autoimmunity and malignancies. The incidence of autoimmune disease in CVID patients may approach 20% of cases. The most common autoimmune disease found in CVID patients is autoimmune cytopenia, but rheumatoid arthritis, lupus, and now primary biliary cirrhosis hav...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2014.04.006
更新日期：2014-08-01 00:00:00
abstract：:Early studies on vitamin D showed promise that various forms of the "vitamin" may be protective against chronic disease, yet systematic reviews and longer-term studies have failed to confirm these findings. A number of studies have suggested that patients with autoimmune diagnoses are deficient in 25-hydroxyvitamin D ...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2009.02.011
更新日期：2009-07-01 00:00:00
abstract：OBJECTIVE:To assess the effectiveness of anti-TNFalpha agents by analysing the principal clinical outcomes in patients with active rheumatoid arthritis (RA). METHODS:1010 patients who received no clinical benefit from previous treatment with methotrexate and/or other DMARDs, were subsequently treated with one or more ...
journal_title：Autoimmunity reviews
pub_type： 临床试验,杂志文章
doi：10.1016/j.autrev.2008.11.001
更新日期：2009-01-01 00:00:00
abstract：:The loss of immune tolerance to self antigens leads to the development of autoimmune responses. Since self antigens are often multiple and/or their sequences may be known, one approach to restore immune tolerance uses synthetic artificial peptides that interfere or compete with self peptides in the networks of cellula...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2010.08.017
更新日期：2010-11-01 00:00:00
abstract：:Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis predominantly targeting medium-sized arteries. PAN is a rare form of vasculitis, and the precise frequency of this disease is difficult to determine. The major environmental factor associated with PAN is HBV infection. The pathogenesis of "idiopathic PAN"...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2016.02.015
更新日期：2016-06-01 00:00:00
abstract：BACKGROUND:Adrenal insufficiency (AI) is associated with high morbidity and mortality. The aim of this systematic review was to enhance diagnostic approaches and summarize therapeutic strategies in the management of AI in patients with systematic lupus erythematosus (SLE) or antiphospholipid syndrome (APS). METHODS:A ...
journal_title：Autoimmunity reviews
pub_type： 杂志文章
doi：10.1016/j.autrev.2018.06.014
更新日期：2019-01-01 00:00:00
abstract：:Blau syndrome (BS) is a rare familial disease transmitted as an autosomal dominant trait, characterized by arthritis, uveitis, skin rash and granulomatous inflammation. Until now BS has been observed in 136 persons belonging to 28 families as well as in 4 sporadic cases. The gene responsible for BS has recently been i...
journal_title：Autoimmunity reviews
pub_type： 杂志文章
doi：10.1016/j.autrev.2008.07.034
更新日期：2009-01-01 00:00:00
abstract：:Analysis of autoantibodies (AAB) by indirect immunofluorescence (IIF) remains the hallmark of diagnosing autoimmune diseases despite the introduction of multiplex techniques. Non-organ specific AAB are screened in routine diagnostics by IIF on HEp-2 cells. However, IIF results vary due to objective (e.g., cell fixatio...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2009.02.033
更新日期：2009-09-01 00:00:00
abstract：:The aim of this work was to review the inflammatory factors involved in central nervous system (CNS) inflammation and the damage associated to their participation in an inflammatory disease of CNS, multiple sclerosis in humans and experimental allergic encephalomyelitis in the murine model. Inflammation has an importa...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2003.09.006
更新日期：2004-06-01 00:00:00
abstract：OBJECTIVE:Toll-like receptor (TLR) 4 (+896 A/G) gene polymorphism has been reported to be associated with susceptibility to giant cell arteritis (GCA) with inconsistent results. To provide a more definitive conclusion, a cumulative meta-analysis of the association of TLR4 (+896 A/G) polymorphism with GCA susceptibility...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,meta分析
doi：10.1016/j.autrev.2011.06.002
更新日期：2011-10-01 00:00:00
abstract：:Autoimmune rheumatic diseases (ARD) are prevalent in women during their childbearing age. For their treatment, high doses of corticosteroid (CS) for long-term periods are often required, increasing the risk of bone loss. According to recent guidelines, bisphosphonates (BP) should be used as first line treatment to pre...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2010.03.002
更新日期：2010-06-01 00:00:00
abstract：:The impact of dietary interventions such as specific types of diet or nutritional supplements in rheumatoid arthritis (RA) has been subject to increased attention in recent years. The recognition of the unmet need to better understand the effects of specific dietary interventions on disease outcomes in RA, along with ...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2018.06.007
更新日期：2018-11-01 00:00:00
abstract：:Mesenchymal stem cells (MSCs) are non-hematopoietic, multipotent progenitor cells which can be isolated from various human adult tissues. In recent years, MSCs have been shown to possess broad immunoregulatory capabilities, modulating both adaptive and innate immunity. This review discusses the documented immunomodula...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2011.01.005
更新日期：2011-05-01 00:00:00
abstract：:Survivin is a protein functionally important for cell division, apoptosis, and possibly, for micro-RNA biogenesis. It is an established marker of malignant cell transformation. In non-malignant conditions, the unique properties of survivin make it indispensable for homeostasis of the immune system. Indeed, it is requi...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2017.05.016
更新日期：2017-08-01 00:00:00
abstract：:Multidrug resistance-1 (MDR-1) is characterized by overfunction of P-glycoprotein (P-gp), a pump molecule that decreases intracellular drug concentration by effluxing them from the intracellular space. Broad ranges of structurally unrelated compounds are transported by P-gp, including antineoplastic agents, HIV protea...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2003.08.002
更新日期：2004-03-01 00:00:00
abstract：:Vascular endothelial injury in Systemic Sclerosis (SSc) leads to pathological changes in the blood vessels that adversely impact the physiology of many organs, resulting in chronic tissue ischemia. The response to hypoxia induces complex cellular and molecular mechanisms in the attempt to recover endothelial cell func...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2011.04.016
更新日期：2011-08-01 00:00:00
abstract：:NMO-IgG, the auto-antibody specific to the aquaporin-4 (AQP4) water channel associated with the autoimmune inflammatory disease neuromyelitis optica (NMO), is considered to be an accurate serum biomarker and is thought to be an important contributor to NMO pathology. In this review, we summarize recent evidences from ...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2009.04.004
更新日期：2009-12-01 00:00:00
abstract：:Antineutrophil cytoplasmic autoantibodies (ANCA) directed to proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) are closely associated with the idiopathic systemic necrotizing vasculitides, in particular Wegener's granulomatosis, microscopic polyangiitis and its renal limited manifestation, and Churg Strauss Syndro...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/s1568-9972(01)00008-8
更新日期：2002-02-01 00:00:00
abstract：:Microscopic polyangiitis (MPA) is a member of the family of ANCA-associated vasculitides. Its characteristic histology shows a necrotizing small vessel vasculitis with little or absent immune deposits (pauci-immune vasculitis). In Western countries MPA shows a lower prevalence than Wegener's disease, it affects more m...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2010.07.009
更新日期：2010-10-01 00:00:00
abstract：OBJECTIVE:We investigated the effectiveness of rituximab (an anti-CD20 monoclonal antibody) in patients with eosinophilic granulomatosis with polyangiitis (EGPA). METHODS:We performed a systematic literature review from the inception dates until July 20, 2020 for articles reporting rituximab administration to treat EG...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2020.102737
更新日期：2021-02-01 00:00:00
abstract：:Autoimmune diseases are a complex set of diseases characterized by immune system activation and, although many progresses have been done in the last 15years, several unmet needs in the management of these patients may be still identified. Recently, a panel of international Experts, divided in different working groups ...
journal_title：Autoimmunity reviews
pub_type： 共识发展会议,杂志文章,评审
doi：10.1016/j.autrev.2017.07.012
更新日期：2017-09-01 00:00:00
abstract：INTRODUCTION:Spondyloarthrits (SpA) share clinical, genetic and immunological features with Inflammatory Bowel Diseases (IBD), and enteropathic SpA (eSpA) represent the clinical evidence of the association between gut and joint diseases. This cross-sectional study aimed to report data of eSpA patients collected from th...
journal_title：Autoimmunity reviews
pub_type： 杂志文章
doi：10.1016/j.autrev.2019.102457
更新日期：2020-02-01 00:00:00
abstract：:To enable clinicians to use autoantibody tests sensibly and economically, laboratories providing the test service have a responsibility to supply the test 'specifications'. This should include information about the test's validity and reliability, its normal range or range within a control population, its sensitivity ...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/s1568-9972(02)00061-7
更新日期：2002-10-01 00:00:00
abstract：:Systemic lupus erythematosus (SLE) is prototypic autoimmune disease characterized by the production of autoantibodies to DNA among other nuclear molecules. These antibodies can form immune complexes that promote pathogenesis by stimulating cytokine production and depositing in the kidney to instigate nephritis. The an...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2010.07.007
更新日期：2010-11-01 00:00:00
abstract：BACKGROUND:Myositis is a heterogeneous group of muscular auto-immune diseases with clinical and pathological criteria that allow the classification of patients into different sub-groups. Inclusion body myositis is the most frequent myositis above fifty years of age. Diagnosing inclusion body myositis requires expertise...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2019.02.003
更新日期：2019-04-01 00:00:00
abstract：:Pernicious anemia (PA) is a complex disorder consisting of hematological, gastric and immunological alterations. Diagnosis of PA relies on histologically proven atrophic body gastritis, peripheral blood examination showing megaloblastic anemia with hypersegmented neutrophils, cobalamin deficiency and antibodies to int...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2014.01.042
更新日期：2014-04-01 00:00:00
abstract：:New biologic agents have changed the paradigm of rheumatoid arthritis treatment, leading to improvement in managing patients' refractory to classical DMARDs. Anti-TNF-alpha is used as first-line treatment in patients failing to respond to classical DMARDs. However, up to 50% of patients fail to respond to these drugs ...
journal_title：Autoimmunity reviews
pub_type： 杂志文章
doi：10.1016/j.autrev.2009.12.010
更新日期：2010-04-01 00:00:00
