Abstract：
:The classical autoimmunity paradigm in rheumatoid arthritis (RA) is strongly supported by immunogenetics suggesting follicular helper T-cell responses driving high titre specific autoantibodies that pre-dates disease onset. Using the immunological disease continuum model of inflammation against self with "pure" adaptive and innate immune disease at opposite boundaries, we propose a novel immune mechanistic classification describing the heterogeneity within RA. Mutations or SNPs in autoinflammatory genes including MEFV and NOD2 are linked to seronegative RA phenotypes including some so called palindromic RA cases. However, just as innate and adaptive immunity are closely functionally integrated, some ACPA+ RA cases have superimposed "autoinflammatory" features including abrupt onset attacks, severe attacks, self-limiting attacks, relevant autoinflammatory mutations or SNPs and therapeutic responses to autoinflammatory pathway therapies including colchicine and IL-1 pathway blockade. An emergent feature from this classification that non-destructive RA phenotypes, both innate and adaptive, have disease epicentres situated in the extracapsular tissues. This mixed innate and adaptive immunopathogenesis may be the key to understanding severe disease flares, resistant disease subsets that are unresponsive to standard therapy and for therapies that target the autoinflammatory component of disease that are not currently considered by expert therapeutic recommendations.
journal_name
Autoimmun Revjournal_title
Autoimmunity reviewsauthors
McGonagle D,Watad A,Savic Sdoi
10.1016/j.autrev.2018.06.001subject
Has Abstractpub_date
2018-11-01 00:00:00pages
1115-1123issue
11eissn
1568-9972issn
1873-0183pii
S1568-9972(18)30203-9journal_volume
17pub_type
杂志文章,评审abstract：:Dermatomyositis (DM), polymyositis (PM), and sporadic inclusion-body myositis (sIBM) constitute a heterogeneous group of subacute or chronic acquired skeletal muscle diseases. Known as idiopathic inflammatory myopathies (IIM), they all share the presence of considerable weakness due to muscle inflammation and necrosis...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2009.11.006
更新日期：2010-03-01 00:00:00
abstract：:Systemic sclerosis (SSc) or scleroderma is a disorder of the connective tissue affecting the skin, and it is often associated with visceral involvement. The predominant pathological features of SSc are autoimmunity, vasculopathy, and fibrosis. Progressive fibrosis is associated with changes in the microcirculation of ...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2017.07.018
更新日期：2017-10-01 00:00:00
abstract：:TNF-alpha is a crucial cytokine in the establishment and maintenance of inflammation in multiple autoimmune and non-autoimmune disorders. A number of large placebo-controlled trials have shown that infliximab, a chimeric monoclonal antibody against TNF-alpha, is effective and well-tolerated in patients with Crohn's di...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2004.08.004
更新日期：2005-03-01 00:00:00
abstract：:Myasthenia gravis is caused by antibodies to the acetylcholine receptor, muscle-specific kinase, low-density lipoprotein receptor-related protein 4, or possibly yet unidentified antibodies. The mechanisms by which these antibodies interfere with the function of postsynaptic proteins include complement activation, anti...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2013.03.001
更新日期：2013-07-01 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：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：:The complement system is profoundly involved in the pathogenesis of acetylcholine receptor (AChR) antibody (Ab) related myasthenia gravis (MG) and its animal model experimental autoimmune myasthenia gravis (EAMG). The most characteristic finding of muscle pathology in both MG and EAMG is the abundance of IgG and compl...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2013.03.003
更新日期：2013-07-01 00:00:00
abstract：:Systemic rheumatic diseases (SRDs) are associated with accelerated atherosclerosis. It has recently been recognised that chronic inflammation is an important factor in the development of atherosclerotic plaque and endothelial dysfunction. The levels of biomarkers such as serum pentraxin 3 (PTX3), an innate immunity pr...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2010.08.001
更新日期：2010-10-01 00:00:00
abstract：:Beta2-glycoprotein I (beta2-GPI) is a major antigen for antiphospholipid antibodies (aPL) present in patients with antiphospholipid syndrome (APS). Oxidized low-density lipoprotein (oxLDL) is subsequently targeted by beta2-GPI and anti-beta2-GPI autoantibodies. Ligands specific for beta2-GPI derived from oxLDL have be...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/s1568-9972(02)00084-8
更新日期：2002-12-01 00:00:00
abstract：:The severe form of COVID-19 share several clinical and laboratory features with four entities gathered under the term "hyperferritinemic syndromes" and including macrophage activation syndrome (MAS), adult-onset Still's disease (AOSD), catastrophic anti-phospholipid syndrome (CAPS) and septic shock. COVID-19 systemic ...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2020.102573
更新日期：2020-07-01 00:00:00
abstract：:Menopause represents a time of significant clinical and hormonal change. Given the incompletely understood interrelationship between gonadal hormones and the immune system, it is possible that menopause may affect, or be affected by, the presence of autoimmune disease. Menopause has significant effects on a number of ...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2011.11.006
更新日期：2012-05-01 00:00:00
abstract：:Kawasaki disease (KD) is a vasculitis that affects mainly children of 6 months to 4 years old. It is important to be early recognised so as to limit the inflammatory cascade that may lead to aneurysmatic dilatations of coronary arteries. The causative agent of KD has not been still indentified and the aetiopathogeneti...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2011.04.005
更新日期：2011-07-01 00:00:00
abstract：:T cells from patients with SLE produce decreased amounts of interleukin-2 (IL-2), a central cytokine in the regulation of the immune response. We discuss herein the abnormalities underlying IL-2 deficiency in SLE T cells. ...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2005.08.009
更新日期：2006-02-01 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：:Differentiation of epithelial cells is required to define tissue architecture and appropriate function of these cells is associated with a specific pattern of gene expression. DNA methylation, post-translational modification of histones and chromatin remodeling are nuclear mechanisms implicated in epigenetic control o...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2010.09.022
更新日期：2011-01-01 00:00:00
abstract：:Neuropsychiatric syndromes are prevalent in pediatric patients with systemic lupus erythematosus (SLE) and often manifest early in disease course and with significant associated morbidity. Postulated pathogenic mechanisms of peripheral and central nervous system events include vasculopathy, autoantibody effects and sy...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2006.08.003
更新日期：2007-03-01 00:00:00
abstract：:A few scores predicting the short-term risk of mortality in Systemic sclerosis (SSc) have been reported to date. Our study aimed to create a predictive 15-year all-cause mortality score at the time of the diagnosis of SSc. The study was based on the Spanish Scleroderma Registry (RESCLE). The cohort was split up in der...
journal_title：Autoimmunity reviews
pub_type： 杂志文章
doi：10.1016/j.autrev.2020.102507
更新日期：2020-05-01 00:00:00
abstract：BACKGROUND:Ferritin and prolactin have been associated with active autoimmune diseases as systemic lupus erythematosus and autoantibody production, but have been little studied in viral infections that present autoimmunity. OBJECTIVE:To investigate the association of these two autoimmune mediators with the presence of...
journal_title：Autoimmunity reviews
pub_type： 杂志文章
doi：10.1016/j.autrev.2010.10.003
更新日期：2011-02-01 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：:The presence of anti-nuclear antibodies (ANA) is a hallmark of systemic autoimmune rheumatic diseases (SARD). The indirect immunofluorescence (IIF) assay on HEp-2 cells is a commonly used test for the detection of ANA and was recently recommended as the screening test of choice by a task force of the American College ...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2011.11.005
更新日期：2012-07-01 00:00:00
abstract：:Henoch-Schönlein purpura is the most common systemic vasculitis in childhood, characterized by the presence of immunoglobulin A deposits in the small vessels of skin, gastrointestinal tube, joints and kidneys. Although there have been great efforts made in elucidating its pathogenic mechanisms, Henoch-Schönlein purpur...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2013.04.003
更新日期：2013-08-01 00:00:00
abstract：OBJECTIVE:To assess the effectiveness and safety of a protocol using medium doses of prednisone to treat lupus nephritis. METHODS:Patients receiving the 'Cruces-protocol cohort' (CPC) were paired 1:2 with patients from the 'historic cohort' (HC). The CPC received medium doses of prednisone combined with methyl-prednis...
journal_title：Autoimmunity reviews
pub_type： 杂志文章
doi：10.1016/j.autrev.2013.10.013
更新日期：2014-02-01 00:00:00
abstract：:As autoantibodies bind to target tissues, Fc-region dependent inflammation can induce pain via mediators exciting nociceptors. But recently another possibility has emerged, where autoantibody binding to nociceptors can directly cause pain, without inflammation. This is thought to occur as a result of Fab-region mediat...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2016.02.011
更新日期：2016-06-01 00:00:00
abstract：:Dendritic cells (DCs) constitute a heterogeneous population of professional antigen presenting cells which are the initiators and key regulators for both immunity and tolerance induction. The significance and impact of DC biology in contemporary immunology and medical research is heightened by the award of the 2011 No...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2012.03.004
更新日期：2012-10-01 00:00:00
abstract：:Viral infections are involved in the pathogenesis of blood autoimmune diseases such as hemolytic anemia and thrombocytopenia. Although antigenic mimicry has been proposed as a major mechanism by which viruses could trigger the development of such diseases, it is not easy to understand how widely different viruses migh...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2004.11.010
更新日期：2005-04-01 00:00:00
abstract：:In the past decade significant advantages have been made in the treatment of rheumatoid arthritis (RA) and therapeutic strategies have changed a lot. These days, highly effective disease modifying anti-rheumatic drugs enable intervention early in the disease process, in order to prevent major joint damage. For years, ...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2005.02.001
更新日期：2005-07-01 00:00:00
abstract：:Autoimmunity is influenced by multiple factors including gender and sex hormones. A definite female predominance is found in many autoimmune diseases. Gender is also associated with differences in clinical presentation, onset, progression and outcome of autoimmune diseases. Sex hormones might influence the target orga...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2011.11.001
更新日期：2012-05-01 00:00:00
abstract：:The concept of undifferentiated spondyloarthritis has been introduced recently to describe a clinical setting where the classical features of spondyloarthritis (SpA) are not fully present. Whether this is a discrete entity was the basis of a debate during the 4th International Congress on Controversies in Rheumatology...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2017.11.006
更新日期：2018-01-01 00:00:00
abstract：:Some thyroid, rheumatic and hepatic diseases consistently have high female:male ratios, but many autoimmune diseases do not. Gonadal hormones, if they play a role in determining sex ratios, likely do so through a threshold or permissive mechanism. Sex differences related to X-inactivation, imprinting, X or Y chromosom...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/s1568-9972(02)00034-4
更新日期：2002-05-01 00:00:00
abstract：:Experimental analyses and literature survey reveal low-redundancy to the host proteins as a common denominator of immunogenic sequences mapped along tumor-, autoimmune-, and infectious disease-associated-proteins. The hypothesis that immunogenicity of peptide sequences is linked to proteomic redundancy is discussed. ...
journal_title：Autoimmunity reviews
pub_type： 杂志文章,评审
doi：10.1016/j.autrev.2006.09.004
更新日期：2007-04-01 00:00:00
