Transitional B cells in quiescent SLE: An early checkpoint imprinted by IFN.

Abstract:

:Systemic lupus (SLE) is characterized by a break of B cell tolerance that plays a central role in disease pathophysiology. An early checkpoint defect occurs at the transitional stage leading to the survival of autoreactive B cells and consequently the production of pathogenic autoantibodies. The main purpose of our work was to determine whether transitional B cells, as the most immature naïve B cell subset upstream of pathogenic B cells, display specific features compared to healthy non SLE subjects. Through extensive analysis of transitional B cells from untreated or low treated, mostly Caucasian, SLE patients, we demonstrated that transitional (T1 and T2) B cell frequencies were increased in SLE and positively correlated with disease activity. SLE transitional B cells displayed defects in two closely inter-related molecules (i.e. TLR9 defective responses and CD19 downregulation). RNA sequencing of sorted transitional B cells from untreated patients revealed a predominant overexpression of interferon stimulated genes (ISGs) even out of flares. In addition, early transitional B cells from the bone marrow displayed the highest interferon score, reflecting a B cell interferon burden of central origin. Hence, the IFN signature in transitional B cells is not confined to African American SLE patients and exists in quiescent disease since the medullary stage. These results suggest that in SLE these 3 factors (i.e. IFN imprintment, CD19 downregulation and TLR9 responses impairment) could take part at the early transitional B cell stage in B cell tolerance by-pass, ultimately leading in periphery to the expansion of autoantibodies-secreting cells.

journal_name

J Autoimmun

journal_title

Journal of autoimmunity

authors

Dieudonné Y,Gies V,Guffroy A,Keime C,Bird AK,Liesveld J,Barnas JL,Poindron V,Douiri N,Soulas-Sprauel P,Martin T,Meffre E,Anolik JH,Korganow AS

doi

10.1016/j.jaut.2019.05.002

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

150-158

eissn

0896-8411

issn

1095-9157

pii

S0896-8411(19)30183-0

journal_volume

102

pub_type

杂志文章
  • Polymyalgia rheumatica--diagnosis and classification.

    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

    authors: Nesher G

    更新日期:2014-02-01 00:00:00

  • Complete suppression of insulitis and diabetes in NOD mice lacking interferon regulatory factor-1.

    abstract::Interferon regulatory factor-1 (IRF-1), a transcriptional factor, regulates type I interferon and interferon-induced genes. It was reported that IRF-1 regulates important molecules required for inflammation and immune reactions. To investigate the role of IRF-1 in the development of autoimmune diabetes, we established...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章

    doi:10.1006/jaut.2001.0531

    authors: Nakazawa T,Satoh J,Takahashi K,Sakata Y,Ikehata F,Takizawa Y,Bando SI,Housai T,Li Y,Chen C,Masuda T,Kure S,Kato I,Takasawa S,Taniguchi T,Okamoto H,Toyota T

    更新日期:2001-09-01 00:00:00

  • Autoantibody repertoire to Ro/SSA and La/SSB antigens in patients with primary and secondary Sjögren's syndrome.

    abstract::Autoimmune diseases are characterized serologically by the presence of antibodies to specific autoantigens. Antibodies to the two antigens Ro/SSA and La/SSB are found in patients with primary (pSS) and secondary Sjögren's syndrome (sSS). To explore if differences in the fine specificity of these autoantibodies could b...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章

    doi:10.1006/jaut.1996.0072

    authors: Wahren M,Solomin L,Pettersson I,Isenberg D

    更新日期:1996-08-01 00:00:00

  • Type 1 cytokines polarize thymocytes during T cell development in adult thymus organ cultures.

    abstract::Peripheral T cells can be polarized towards type 1 or type 2 cytokine immune responses during TCR engagement. Because T cell selection by peptide plus self-MHC in the thymus requires TCR engagement, we hypothesized that type 1 cytokines may polarize developing T cells. We cultured thymi from BBDR rats in adult thymus ...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章

    doi:10.1016/s0896-8411(02)00091-4

    authors: Whalen BJ,Marounek J,Mordes JP,Rossini AA,Greiner DL

    更新日期:2003-02-01 00:00:00

  • Targeting CD6 for the treatment of experimental autoimmune uveitis.

    abstract:OBJECTIVE:CD6 is emerging as a new target for treating many pathological conditions in which T cells are integrally involved, but even the latest data from studies of CD6 gene engineered mice were still contradictory. To address this issue, we studied experimental autoimmune uveitis (EAU), a model of autoimmune uveitis...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章

    doi:10.1016/j.jaut.2018.02.004

    authors: Zhang L,Li Y,Qiu W,Bell BA,Dvorina N,Baldwin WM 3rd,Singer N,Kern T,Caspi RR,Fox DA,Lin F

    更新日期:2018-06-01 00:00:00

  • Systemic lupus erythematosus: Diagnosis and clinical management.

    abstract::Systemic lupus erythematosus (SLE) is a worldwide chronic autoimmune disease which may affect every organ and tissue. Genetic predisposition, environmental triggers, and the hormonal milieu, interplay in disease development and activity. Clinical manifestations and the pattern of organ involvement are widely heterogen...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章,评审

    doi:10.1016/j.jaut.2018.11.001

    authors: Fava A,Petri M

    更新日期:2019-01-01 00:00:00

  • 'Anergic' T cells modulate the T-cell activating capacity of antigen-presenting cells.

    abstract::Nowadays there is compelling evidence for immunoregulation by T cells. Recently, we showed that so-called 'anergic' T cells are not functionally inert but can act as regulatory cells by actively suppressing other T cell responses. We now show that 'anergic' T cells mediate this suppressive effect via modulation of the...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章

    doi:10.1006/jaut.2000.0372

    authors: Taams LS,Boot EP,van Eden W,Wauben MH

    更新日期:2000-06-01 00:00:00

  • Cell and gene therapy using mesenchymal stem cells (MSCs).

    abstract::Mesenchymal stem cells (MSCs) are considered to be a promising platform for cell and gene therapy for a variety of diseases. First, in the field of hematopoietic stem cell transplantation, there are two applications of MSCs: 1) the improvement of stem cell engrafting and the acceleration of hematopoietic reconstitutio...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章,评审

    doi:10.1016/j.jaut.2007.12.008

    authors: Ozawa K,Sato K,Oh I,Ozaki K,Uchibori R,Obara Y,Kikuchi Y,Ito T,Okada T,Urabe M,Mizukami H,Kume A

    更新日期:2008-05-01 00:00:00

  • Low levels of IgM antibodies to phosphorylcholine predict cardiovascular disease in 60-year old men: effects on uptake of oxidized LDL in macrophages as a potential mechanism.

    abstract:OBJECTIVE:We here determine the role of IgM antibodies against phosphorylcholine (anti-PC) in prediction of cardiovascular disease (CVD) and on macrophage uptake of Oxidized LDL (OxLDL). METHODS:From a screening of 4232 subjects, 60-year-old (2039 men and 2193 women), 211 incident cases of CVD (myocardial infarction, ...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章

    doi:10.1016/j.jaut.2009.05.003

    authors: de Faire U,Su J,Hua X,Frostegård A,Halldin M,Hellenius ML,Wikström M,Dahlbom I,Grönlund H,Frostegård J

    更新日期:2010-03-01 00:00:00

  • Clinical features and biochemical data of Caucasian children at diagnosis of autoimmune hepatitis.

    abstract:OBJECTIVE:Evaluation of systematic epidemiological data regarding clinical characteristics, sex distribution and autoantibody pattern in Caucasian children with autoimmune hepatitis (AIH). STUDY DESIGN:Data of 142 children presenting with AIH (97 girls and 45 boys) have been analysed for their clinical, serological, a...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章

    doi:10.1016/j.jaut.2004.11.009

    authors: Oettinger R,Brunnberg A,Gerner P,Wintermeyer P,Jenke A,Wirth S

    更新日期:2005-02-01 00:00:00

  • The mimicry of human glycolipids and glycosphingolipids by the lipooligosaccharides of pathogenic neisseria and haemophilus.

    abstract::It has been known for many years that bacteria can induce autoimmune responses in humans resulting in serious disease. Recent work has shown that a number of bacteria that colonize human mucosal surfaces exclusively express antigens on their surfaces which are molecular mimics of glycosphingolipids found on human cell...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章,评审

    doi:10.1006/jaut.2000.0477

    authors: Harvey HA,Swords WE,Apicella MA

    更新日期:2001-05-01 00:00:00

  • Lack of relationship between the Epstein-Barr virus and the antiperinuclear factor/'perinuclear antigen' system in rheumatoid arthritis.

    abstract::Our purpose was to evaluate the role of Epstein-Barr virus (EBV) in the production of antiperinuclear factor (APF), a rheumatoid arthritis (RA)-specific marker, and the autoimmunogenicity of 'perinuclear antigens' (PNA) found within the buccal mucosa epithelial cells used as a substrate in the APF assay. Fifty APF-pos...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章

    doi:10.1006/jaut.1994.1035

    authors: Buisson M,Berthelot JM,Le Goff P,Chastel C,Lamour A,Seigneurin JM,Youinou P

    更新日期:1994-08-01 00:00:00

  • Prevention of diabetes and insulitis by neonatal intrathymic islet administration in NOD mice.

    abstract::The murine model of human insulin dependent diabetes mellitus (IDDM), the non-obese diabetic (NOD) mouse, develops a T cell-dependent destruction of pancreatic islets. While the target antigens are unknown, there is clearly a lack of tolerance to them. Neonatal intrathymic (i.t.) antigen injection has been successfull...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章

    doi:10.1006/jaut.1994.1040

    authors: Charlton B,Taylor-Edwards C,Tisch R,Fathman CG

    更新日期:1994-10-01 00:00:00

  • Emergence of long-lived autoreactive plasma cells in the spleen of primary warm auto-immune hemolytic anemia patients treated with rituximab.

    abstract::Primary warm autoimmune hemolytic anemia (wAIHA) is a rare autoimmune disease in which red blood cells are eliminated by IgG autoantibodies. We analyzed the antibody-secreting cells in the spleen and the peripheral blood of wAIHA patients in various contexts of treatment. Plasmablasts were observed in peripheral blood...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章

    doi:10.1016/j.jaut.2015.05.006

    authors: Mahévas M,Michel M,Vingert B,Moroch J,Boutboul D,Audia S,Cagnard N,Ripa J,Menard C,Tarte K,Mégret J,Le Gallou S,Patin P,Thai L,Galicier L,Bonnotte B,Godeau B,Noizat-Pirenne F,Weill JC,Reynaud CA

    更新日期:2015-08-01 00:00:00

  • IgA-containing immune complexes in the circulation of patients with primary Sjögren's syndrome.

    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

    authors: Bendaoud B,Pennec YL,Lelong A,Le Noac'h JF,Magadur G,Jouquan J,Youinou P

    更新日期:1991-02-01 00:00:00

  • The clinical features, diagnosis and classification of dermatomyositis.

    abstract::Dermatomyositis (DM) is an idiopathic inflammatory myopathy (IIM) characterized by an inflammatory infiltrate primarily affecting the skeletal muscle and skin. Most common and peculiar cutaneous lesions include Gottron's papules, Gottron's sign and heliotrope rash. Different DM subsets have been identified until now e...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章,评审

    doi:10.1016/j.jaut.2013.11.005

    authors: Iaccarino L,Ghirardello A,Bettio S,Zen M,Gatto M,Punzi L,Doria A

    更新日期:2014-02-01 00:00:00

  • Metagenomic profiling of the pro-inflammatory gut microbiota in ankylosing spondylitis.

    abstract:OBJECTIVE:Gut dysbiosis has been reported implicated in ankylosing spondylitis (AS), a common chronic inflammatory disease mainly affects sacroiliac joints and spine. Utilizing deep sequencing on the feces of untreated AS patients, our study aimed at providing an in-depth understanding of AS gut microbiota. METHODS:We...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章

    doi:10.1016/j.jaut.2019.102360

    authors: Zhou C,Zhao H,Xiao XY,Chen BD,Guo RJ,Wang Q,Chen H,Zhao LD,Zhang CC,Jiao YH,Ju YM,Yang HX,Fei YY,Wang L,Shen M,Li H,Wang XH,Lu X,Yang B,Liu JJ,Li J,Peng LY,Zheng WJ,Zhang CY,Zhou JX,Wu QJ,Yang YJ,Su

    更新日期:2020-02-01 00:00:00

  • Autoantibodies from Sjögren's syndrome induce activation of both the intrinsic and extrinsic apoptotic pathways in human salivary gland cell line A-253.

    abstract::Sjögren's syndrome (SS) is an autoimmune rheumatic disease that targets salivary and lachrymal glands, characterized by a high concentration of serum autoantibodies directed against nuclear and cytoplasmic antigens. It is known that autoantibodies can enter viable cells and this phenomenon has functional consequences ...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章

    doi:10.1016/j.jaut.2006.05.001

    authors: Sisto M,Lisi S,Castellana D,Scagliusi P,D'Amore M,Caprio S,Scagliusi A,Acquafredda A,Panaro MA,Mitolo V

    更新日期:2006-08-01 00:00:00

  • Early events in islets and pancreatic lymph nodes in autoimmune diabetes.

    abstract::The specific contributions of islet cell microenvironment during the development of autoimmune type 1 diabetes remain unclear. The aims of this study were to identify early immune-driven abnormalities in islets and pancreatic lymph nodes of NOD mice by cDNA arrays. We compared gene expression profiles of purified isle...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章

    doi:10.1016/j.jaut.2004.03.007

    authors: Aspord C,Rome S,Thivolet C

    更新日期:2004-08-01 00:00:00

  • Clinical characteristics and predictors of survival in adults with coronavirus disease 2019 receiving tocilizumab.

    abstract::Coronavirus disease 2019 (COVID-19) can progress to cytokine storm that is associated with organ dysfunction and death. The purpose of the present study is to determine clinical characteristics associated with 28 day in-hospital survival in patients with coronavirus disease 2019 (COVID-19) that received tocilizumab. T...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章,多中心研究

    doi:10.1016/j.jaut.2020.102512

    authors: Morrison AR,Johnson JM,Griebe KM,Jones MC,Stine JJ,Hencken LN,To L,Bianchini ML,Vahia AT,Swiderek J,Ramesh MS,Peters MA,Smith ZR

    更新日期:2020-11-01 00:00:00

  • Isolation and characterization of two human monoclonal anti-phospholipid IgG from patients with autoimmune disease.

    abstract::The antigenic specificity of anti-phospholipid antibodies (APA) is a matter of intensive investigation. To further characterize these antibodies, we attempted to isolate human monoclonal APA. B-cells of patients with at least one positive test for antibodies against cardiolipin, phosphatidylserine, beta2-glycoprotein ...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章

    doi:10.1006/jaut.1999.0316

    authors: von Landenberg C,Lackner KJ,von Landenberg P,Lang B,Schmitz G

    更新日期:1999-09-01 00:00:00

  • Autoantibodies with enzymatic properties in human autoimmune diseases.

    abstract::Immunoglobulins (Ig) or antibodies are heavy plasma proteins, with sugar chains added to amino acid residues by N-linked glycosylation and occasionally by O-linked glycosylation. The versatility of antibodies is demonstrated by the various functions that they mediate such as neutralization, agglutination, fixation wit...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章,评审

    doi:10.1016/j.jaut.2011.05.007

    authors: Wootla B,Lacroix-Desmazes S,Warrington AE,Bieber AJ,Kaveri SV,Rodriguez M

    更新日期:2011-09-01 00:00:00

  • Breaking peripheral immune tolerance to CNS antigens in neurodegenerative diseases: boosting autoimmunity to fight-off chronic neuroinflammation.

    abstract::Immune cell infiltration to the brain's territory was considered for decades to reflect a pathological process in which immune cells attack the central nervous system (CNS); such a process is observed in the inflammatory autoimmune disease, multiple sclerosis (MS). As neuroinflammatory processes within the CNS parench...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章,评审

    doi:10.1016/j.jaut.2014.08.002

    authors: Schwartz M,Baruch K

    更新日期:2014-11-01 00:00:00

  • Bystander activation and autoimmunity.

    abstract::The interaction over time of genetic, epigenetic and environmental factors (i.e., autoimmune ecology) increases or decreases the liability an individual would have to develop an autoimmune disease (AD) depending on the misbalance between risk and protective effects. Pathogens have been the most common antecedent event...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章,评审

    doi:10.1016/j.jaut.2019.06.012

    authors: Pacheco Y,Acosta-Ampudia Y,Monsalve DM,Chang C,Gershwin ME,Anaya JM

    更新日期:2019-09-01 00:00:00

  • Dendritic cells tip the balance towards induction of regulatory T cells upon priming in experimental autoimmune encephalomyelitis.

    abstract::Counter-balancing regulatory mechanisms, such as the induction of regulatory T cells (Treg), limit the effects of autoimmune attack in neuroinflammation. However, the role of dendritic cells (DCs) as the most powerful antigen-presenting cells, which are intriguing therapeutic targets in this context, is not fully unde...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章

    doi:10.1016/j.jaut.2016.09.008

    authors: Paterka M,Voss JO,Werr J,Reuter E,Franck S,Leuenberger T,Herz J,Radbruch H,Bopp T,Siffrin V,Zipp F

    更新日期:2017-01-01 00:00:00

  • Comparative study of GAD65-specific CD4+ T cells in healthy and type 1 diabetic subjects.

    abstract::Glutamic acid decarboxylase 65 (GAD65) is a putative autoantigen associated with the pathogenesis of type 1 diabetes (T1D). The prevalence of autoreactive CD4+ T cells towards the immunodominant GAD65(555-567) epitope in DR4 healthy and T1D subjects was investigated with class II tetramers. A slightly higher percentag...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章

    doi:10.1016/j.jaut.2005.08.007

    authors: Danke NA,Yang J,Greenbaum C,Kwok WW

    更新日期:2005-12-01 00:00:00

  • Immunogenetics of juvenile idiopathic arthritis: A comprehensive review.

    abstract::Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory arthropathy of childhood. Juvenile idiopathic arthritis is believed to be a complex genetic trait influenced by both genetic and environmental factors. Twin and family studies suggest a substantial role for genetic factors in the predispositio...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章,评审

    doi:10.1016/j.jaut.2015.08.002

    authors: Hersh AO,Prahalad S

    更新日期:2015-11-01 00:00:00

  • Low-dose interleukin-2 fosters a dose-dependent regulatory T cell tuned milieu in T1D patients.

    abstract::Most autoimmune diseases (AID) are linked to an imbalance between autoreactive effector T cells (Teffs) and regulatory T cells (Tregs). While blocking Teffs with immunosuppression has long been the only therapeutic option, activating/expanding Tregs may achieve the same objective without the toxicity of immunosuppress...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.jaut.2015.01.001

    authors: Rosenzwajg M,Churlaud G,Mallone R,Six A,Dérian N,Chaara W,Lorenzon R,Long SA,Buckner JH,Afonso G,Pham HP,Hartemann A,Yu A,Pugliese A,Malek TR,Klatzmann D

    更新日期:2015-04-01 00:00:00

  • The mystery of Sneddon syndrome: relationship with antiphospholipid syndrome and systemic lupus erythematosus.

    abstract::Since its description in 1965, Sneddon syndrome (SNS) is usually characterized by the association of an ischemic cerebrovascular disease and a widespread livedo reticularis. The presence of many other manifestations suggests that it is a systemic syndrome. The prevalence of anti-phospholipid antibodies (aPL) is highly...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章,评审

    doi:10.1006/jaut.2000.0418

    authors: Francès C,Piette JC

    更新日期:2000-09-01 00:00:00

  • 1,25 dihydroxyvitamin-D3 regulation of immunoglobulin production in peripheral blood mononuclear cells of patients with systemic lupus erythematosus.

    abstract::Systemic Lupus Erythematosus (SLE) is a multisystem disease characterized by an increase in the secretion of autoantibodies. The mechanisms of autoantibody-induced disease have not been clarified. 1,25-Dihydroxy-vitamin D3 (1,25-D3) is known to be important in the regulation of normal human lymphocyte functions. Among...

    journal_title:Journal of autoimmunity

    pub_type: 杂志文章

    doi:10.1016/0896-8411(89)90012-7

    authors: Chong PJ,Matzner WL,Wallace DJ,Klinenberg JR,Toyoda M,Jordan SC

    更新日期:1989-12-01 00:00:00