Abstract:
:Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a poorly understood preclinical stage of immune dysregulation and symptom accrual. Accumulation of antinuclear autoantibody (ANA) specificities is a hallmark of impending clinical disease. Yet, many ANA-positive individuals remain healthy, suggesting that additional immune dysregulation underlies SLE pathogenesis. Indeed, we have recently demonstrated that interferon (IFN) pathways are dysregulated in preclinical SLE. To determine if other forms of immune dysregulation contribute to preclinical SLE pathogenesis, we measured SLE-associated autoantibodies and soluble mediators in samples from 84 individuals collected prior to SLE classification (average timespan = 5.98 years), compared to unaffected, healthy control samples matched by race, gender, age (±5 years), and time of sample procurement. We found that multiple soluble mediators, including interleukin (IL)-5, IL-6, and IFN-γ, were significantly elevated in cases compared to controls more than 3.5 years pre-classification, prior to or concurrent with autoantibody positivity. Additional mediators, including innate cytokines, IFN-associated chemokines, and soluble tumor necrosis factor (TNF) superfamily mediators increased longitudinally in cases approaching SLE classification, but not in controls. In particular, levels of B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) were comparable in cases and controls until less than 10 months pre-classification. Over the entire pre-classification period, random forest models incorporating ANA and anti-Ro/SSA positivity with levels of IL-5, IL-6, and the IFN-γ-induced chemokine, MIG, distinguished future SLE patients with 92% (±1.8%) accuracy, compared to 78% accuracy utilizing ANA positivity alone. These data suggest that immune dysregulation involving multiple pathways contributes to SLE pathogenesis. Importantly, distinct immunological profiles are predictive for individuals who will develop clinical SLE and may be useful for delineating early pathogenesis, discovering therapeutic targets, and designing prevention trials.
journal_name
J Autoimmunjournal_title
Journal of autoimmunityauthors
Lu R,Munroe ME,Guthridge JM,Bean KM,Fife DA,Chen H,Slight-Webb SR,Keith MP,Harley JB,James JAdoi
10.1016/j.jaut.2016.06.001subject
Has Abstractpub_date
2016-11-01 00:00:00pages
182-193eissn
0896-8411issn
1095-9157journal_volume
74pub_type
杂志文章abstract::Salivary gland (SG) acinar-cells are susceptible to endoplasmic reticulum (ER) stress related to their secretory activity and the complexity of synthesized secretory products. SGs of Sjögren's syndrome patients (SS)-patients show signs of inflammation and altered proteostasis, associated with low IRE1α/XBP-1 pathway a...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2016.07.006
更新日期:2016-12-01 00:00:00
abstract::IgA-, IgM- and IgG-containing immune complexes (CIC) were detected in 48, 19 and 12% of 52 patients with primary Sjögren's syndrome (SS), in 36, 38 and 56% of 45 patients with rheumatoid arthritis, and in 8, 5 and 3% of 40 normal controls. A high proportion of primary SS patients also had considerable amounts of serum...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(91)90016-6
更新日期:1991-02-01 00:00:00
abstract::B cells are involved in immune thrombocytopenia (ITP) pathophysiology by producing antiplatelet auto-antibodies. However more than a half of ITP patients do not respond to B cell depletion induced by rituximab (RTX). The persistence of splenic T follicular helper cells (TFH) that we demonstrated to be expanded during ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2016.11.002
更新日期:2017-02-01 00:00:00
abstract::Peptidyl arginine deiminases (PADs) catalyze a post-translational protein modification reaction called citrullination, where arginine is converted to citrulline. This modification has been linked to the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA). More recently, several studies have suggest...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2012.03.004
更新日期:2012-06-01 00:00:00
abstract::IL-10 has been shown to be an important anti-inflammatory mediator that has both down-regulatory and immunomodulatory effects. Utilizing IL-10(-/-) mice we demonstrate the induction of low dose oral tolerance characterized by the up-regulation of TGF-beta and IL-4 and the suppression of Ag specific proliferation with ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2004.08.001
更新日期:2004-11-01 00:00:00
abstract::NZB mice demonstrate common and consistent abnormalities in B-cell activation and signalling. One of the hallmark characteristics of lupus disease is the prevalent hypergammaglobulinaemia, composed primarily of anti-nuclear antibodies. In addition to the hyperproliferation seen in mice exhibiting disease, the B cells ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2002.0607
更新日期:2002-11-01 00:00:00
abstract::Antiphospholipid syndrome (APS) is characterized by thrombosis and pregnancy loss in the presence of antiphospholipid antibodies (aPL), mainly anticardiolipin, anti-beta2-glycoprotein I and lupus anticoagulant. However, similar to systemic lupus erythematosus, APS is also characterized by multiple other autoantibodies...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2007.11.011
更新日期:2008-02-01 00:00:00
abstract::The removal of beta(1)-adrenergic receptor (beta(1)AR) autoantibodies by immunoadsorption (IA) has been proposed as a potential mechanism for the improvement of the left ventricular function in dilated cardiomyopathy (DCM). In the present study, the possible association between removal of the autoantibodies against th...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/s0896-8411(03)00042-8
更新日期:2003-06-01 00:00:00
abstract::Wegener's autoantigen (WA), a 29 kD multifunctional protein, is the principal target antigen of autoantibodies associated with Wegener's granulomatosis (WG). WA was first identified as proteinase 3 (PR3), which is now known to be identical with myeloblastin and AGP7. Like other lysosomal proteins, WA/PR3 displays enzy...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1006/jaut.1993.1015
更新日期:1993-04-01 00:00:00
abstract::Following the mass vaccinations against pandemic influenza A/H1N1 virus in 2009, a sudden increase in juvenile onset narcolepsy with cataplexy (NC) was detected in several European countries where AS03-adjuvanted Pandemrix vaccine had been used. NC is a chronic neurological disorder characterized by excessive daytime ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2015.07.006
更新日期:2015-09-01 00:00:00
abstract::Type 1 diabetes is the result of an ongoing autoimmune response to specific proteins expressed by the insulin producing beta cells. Recently, a number of beta cell autoantigens have been identified. However, their role in mediating the diabetogenic response is not known. Here we assess the relative importance of a pan...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1994.1067
更新日期:1994-12-01 00:00:00
abstract::Many mechanisms can explain the mode of action of IVIg in immune disorders. Macrophage blockade and interference in the idiotypic network are supported by some experimental data. Among the other mechanisms, two are considered in greater detail. Firstly, in some disorders, the patients could improve simply because the ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1006/jaut.1993.1057
更新日期:1993-12-01 00:00:00
abstract::Very little is known about the cellular immune response in c-ANCA (classical anti-neutrophil cytoplasm antibodies) positive vasculitides or Wegener's granulomatosis (WG). The present review is mainly based on published and unpublished observations of the Cattegat Study Group of Wegener's Granulomatosis. Immunohistoche...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1006/jaut.1993.1020
更新日期:1993-04-01 00:00:00
abstract::Polymyositis is classified as a separate entity among idiopathic inflammatory myopathies but it is considered as the least common since it is an exclusion diagnosis. This myopathy usually presents with subacute-chronic symmetric proximal limb weakness, although some extramuscular manifestations are common. Creatine ki...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2014.01.025
更新日期:2014-02-01 00:00:00
abstract::A large number of autoimmune diseases (ADs) are more prevalent in women. The more frequent the AD and the later it appears, the more women are affected. Many ideas mainly based on hormonal and genetic factors that influence the autoimmune systems of females and males differently, have been proposed to explain this pre...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2011.10.003
更新日期:2012-05-01 00:00:00
abstract::Sex hormones, including estrogens, influence the immune system in a complex manner, playing an important role in the pathophysiology of autoimmune diseases. Estrogen receptors can be found in almost all cells, including those of the adaptive and innate immune systems. Depending on the relative preponderance and stimul...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2011.11.002
更新日期:2012-05-01 00:00:00
abstract::A recent report identified two islet cell cytoplasmic antibody subclasses using an immunohistochemical method. The islet cell cytoplasmic antibody subclass which reacts with only Beta-cells was termed 'Beta-cell islet cell cytoplasmic antibodies' and another islet cell cytoplasmic antibody subclass which reacts with B...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1994.1028
更新日期:1994-06-01 00:00:00
abstract::Murine monoclonal antibodies (mAb) reacting with affinity-purified antihistone antibodies (AHA) from serum of a patient with systemic lupus erythematosus (SLE) were obtained. One of them, 8B3, was initially considered to recognize idiotypic (Id) determinants in AHA since (a) it reacted with AHA but not with control Ig...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(92)90149-k
更新日期:1992-06-01 00:00:00
abstract::Many years of work, multiplex family collection and endless genotyping finally give fruit. The original aim cannot be lost. The aim is not only to identify mutations involved in susceptibility for systemic lupus erythematosus (SLE) but to elucidate the disease pathogenesis as well. After genetics comes the biology. We...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/s0896-8411(03)00093-3
更新日期:2003-09-01 00:00:00
abstract::Myasthenia gravis (MG) is a prototypical antibody-mediated disease characterized by muscle weakness and fatigability. Serum antibodies to the acetylcholine receptor and muscle-specific tyrosine kinase receptor (MuSK) are found in about 85% and 8% of patients respectively. We have previously shown that more than 70% of...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2013.12.007
更新日期:2014-08-01 00:00:00
abstract::Polymyalgia rheumatica is the most common inflammatory rheumatic disease of the elderly, and shares many pathogenetic and epidemiological features with giant cell arteritis. The typical symptoms are bilateral aching of the shoulder girdle, associated with morning stiffness. The neck and hip girdle may also be involved...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2014.01.016
更新日期:2014-02-01 00:00:00
abstract::The pathogeny of ulcerative colitis (UC) is not yet elucidated, but some arguments suggest the implication of genetic factors. Among the candidate genes, those encoding for HLA class II genotypes have been extensively studied in UC; however, discordant data may be imputable to heterogeneity, characterized by immunolog...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1996.0100
更新日期:1996-12-01 00:00:00
abstract::The adrenocortical response is central to recovery from experimental allergic encephalomyelitis (EAE) in the Lewis rat, as reflected by the increased severity of the disease in adrenalectomized animals. The protection conferred by glucocorticoids is related to the immunosuppressive effects of the steroid, which may in...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1996.0020
更新日期:1996-04-01 00:00:00
abstract::Previous studies have indicated that blood mononuclear cells from 15-20% of patients with systemic lupus erythematosus (SLE) carry elevated levels of hsp90, a heat shock protein associated with steroid receptors in cells. We analysed surface expression of hsp90 on mononuclear cells (lymphocytes and monocytes) from pat...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(92)90194-u
更新日期:1992-12-01 00:00:00
abstract::Autoimmune hepatitis (AIH) is defined as a chronic liver inflammation with loss of tolerance against hepatocytes. The etiology and pathophysiology of AIH are still poorly understood because reliable animal models are limited. Therefore, we recently introduced a model of experimental murine AIH by a self-limited adenov...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2016.12.001
更新日期:2017-03-01 00:00:00
abstract::Proper T cell activation and function are regulated by the innate immune system, importantly through positive and negative costimulatory molecules in the B7 superfamily. Inducible costimulator (ICOS), the receptor for B7h (also known as B7RP-1), is expressed on T cells after T cell activation. Recently, using ICOS-def...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/s0896-8411(03)00119-7
更新日期:2003-11-01 00:00:00
abstract::CD4(+) T cells specific for immunologic non-self determinants on self-IgG, idiotopes (Id), can be raised from cerebrospinal fluid (CSF) and blood of patients with multiple sclerosis (MS). To test if Id-specific CD4(+) T cells have the potential to destroy oligodendrocytes (ODCs), we analyzed their ability to induce ap...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2009.01.004
更新日期:2009-03-01 00:00:00
abstract::New Zealand (NZ) mouse strains comprise both autoimmune and non-autoimmune animals: NZ black (NZB) mice and the F1 hybrid (NZB/W) of NZB and NZ white (NZW) mice show spontaneous autoimmune disease by 6 months of age and die before the first year of age from renal disease, while NZW mice do not show autoimmune disorder...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(92)90160-r
更新日期:1992-10-01 00:00:00
abstract::Dysregulation of autophagy has been implicated in the development of various disease indications including autoimmune diseases. Here we identified hitherto unsuspected molecular alterations of autophagy occurring at an early stage of the macroautophagy pathway in the salivary glands and spleen of NOD.H-2h4 mice that d...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2020.102418
更新日期:2020-03-01 00:00:00
abstract:OBJECTIVE:To compare the efficacy and safety of Disease-modifying antirheumatic drugs (DMARDs) and anti-TNF-α agents in patients with non-infectious non-anterior uveitis. METHODS:Single center retrospective study including adult patients with non-infectious intermediate, posterior or pan-uveitis. Outcomes were compare...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2020.102481
更新日期:2020-09-01 00:00:00