Peptidylarginine deiminase 2, 3 and 4 have distinct specificities against cellular substrates: novel insights into autoantigen selection in rheumatoid arthritis.

Abstract:

OBJECTIVE:To define the relationship between autoantigen citrullination and different peptidylarginine deiminase (PAD) enzymes in rheumatoid arthritis (RA). METHODS:Citrullinated autoantigens were identified by immunoblotting control and ionomycin-activated human primary neutrophil lysate with RA sera. Autoantigen identity and citrullination sites were defined by mass spectrometry. PAD isoenzyme expression in human neutrophils was determined by immunoblotting. PAD substrate specificity was addressed in HL-60 cell lysates co-incubated with human recombinant PAD2, PAD3 and PAD4. RESULTS:Although prominent protein citrullination is observed in ionomycin-activated neutrophils, RA sera only recognised a limited number of these citrullinated molecules. Among these, the authors identified that β and γ-actins are citrullinated on at least 10 arginine residues, generating a novel 47 kDa species that is frequently recognised by RA autoantibodies. Interestingly, the authors showed that the PAD enzymes expressed in human neutrophils (ie, PAD2, PAD3 and PAD4) have unique substrate specificities, independent of their subcellular distribution. Thus, only PAD2 was able to citrullinate native β/γ-actin, while histone H3 was only citrullinated by PAD4. CONCLUSION:These studies identified β and γ-actins as novel citrullinated autoantigens in RA, allowing enzyme specificity against intracellular substrates to be addressed. The studies provide evidence that PAD enzymes have the intrinsic capacity to select unique protein targets. The authors propose that unique PAD specificity may play a role in autoantigen selection in RA.

journal_name

Ann Rheum Dis

authors

Darrah E,Rosen A,Giles JT,Andrade F

doi

10.1136/ard.2011.151712

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

92-8

issue

1

eissn

0003-4967

issn

1468-2060

pii

ard.2011.151712

journal_volume

71

pub_type

杂志文章
  • Wnt16 attenuates osteoarthritis progression through a PCP/JNK-mTORC1-PTHrP cascade.

    abstract:OBJECTIVES:Wnt16 is implicated in bone fracture and bone mass accrual both in animals and humans. However, its functional roles and molecular mechanism in chondrocyte differentiation and osteoarthritis (OA) pathophysiology remain largely undefined. In this study, we analysed its mechanistic association and functional r...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/annrheumdis-2018-214200

    authors: Tong W,Zeng Y,Chow DHK,Yeung W,Xu J,Deng Y,Chen S,Zhao H,Zhang X,Ho KK,Qin L,Mak KK

    更新日期:2019-04-01 00:00:00

  • Risk of diabetes mellitus associated with disease-modifying antirheumatic drugs and statins in rheumatoid arthritis.

    abstract:OBJECTIVE:To investigate the rate of incident diabetes mellitus (DM) in patients with rheumatoid arthritis (RA) and the impact of disease-modifying antirheumatic drug (DMARD) and statin treatments. METHODS:We studied patients with RA and ≥1 year participation in the National Data Bank for Rheumatic Diseases without ba...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/annrheumdis-2016-209954

    authors: Ozen G,Pedro S,Holmqvist ME,Avery M,Wolfe F,Michaud K

    更新日期:2017-05-01 00:00:00

  • Drug-specific risk of non-tuberculosis opportunistic infections in patients receiving anti-TNF therapy reported to the 3-year prospective French RATIO registry.

    abstract:BACKGROUND:Anti-tumour necrosis factor (TNF) therapy may be associated with opportunistic infections (OIs). OBJECTIVE:To describe the spectrum of non-tuberculosis OIs associated with anti-TNF therapy and identify their risk factors. METHODS:A 3-year national French registry (RATIO) collected all cases of OI in patien...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章,多中心研究

    doi:10.1136/ard.2010.137422

    authors: Salmon-Ceron D,Tubach F,Lortholary O,Chosidow O,Bretagne S,Nicolas N,Cuillerier E,Fautrel B,Michelet C,Morel J,Puéchal X,Wendling D,Lemann M,Ravaud P,Mariette X,RATIO group.

    更新日期:2011-04-01 00:00:00

  • Smoking induces transcription of the heat shock protein system in the joints.

    abstract:OBJECTIVES:Smoking increases the risk of developing rheumatoid arthritis (RA) and worsens the course of the disease. In the current study we analysed whether smoking can affect gene expression directly in the joints. METHODS:Synovial fibroblasts were incubated with 5% cigarette smoke extract and changes in gene expres...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/annrheumdis-2013-204486

    authors: Ospelt C,Camici GG,Engler A,Kolling C,Vogetseder A,Gay RE,Michel BA,Gay S

    更新日期:2014-07-01 00:00:00

  • Radiological progression in rheumatoid arthritis: how many patients are required in a treatment trial to test disease modification?

    abstract:OBJECTIVE:To determine whether the number of patients required in a therapeutic trial that uses progression of radiological abnormalities as the outcome measure would be similar for multiple centres. METHODS:The progression of radiological damage to the fingers and wrists of patients with rheumatoid arthritis in five ...

    journal_title:Annals of the rheumatic diseases

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1136/ard.52.5.332

    authors: Sharp JT,Wolfe F,Corbett M,Isomaki H,Mitchell DM,Furst DE,Sibley J,Shipley M

    更新日期:1993-05-01 00:00:00

  • Role of the MHC2TA gene in autoimmune diseases.

    abstract:OBJECTIVES:Expression of major histocompatibility complex (MHC) class II genes is almost exclusively regulated by the class II transactivator. A promoter polymorphism (-168A/G, rs3087456) in the MHC2TA gene was associated with increased susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarctio...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.2006.059428

    authors: Martínez A,Sánchez-Lopez M,Varadé J,Mas A,Martín MC,de Las Heras V,Arroyo R,Mendoza JL,Díaz-Rubio M,Fernández-Gutiérrez B,de la Concha EG,Urcelay E

    更新日期:2007-03-01 00:00:00

  • Reproductive history, hormonal factors and the incidence of hip and knee replacement for osteoarthritis in middle-aged women.

    abstract:OBJECTIVES:To examine the effect of reproductive history and use of hormonal therapies on the risk of hip and knee joint replacement for osteoarthritis. METHODS:A prospective study of 1.3 million women aged on average 56 years at recruitment and followed-up through linkage to routinely collected hospital admission rec...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章,多中心研究

    doi:10.1136/ard.2008.095653

    authors: Liu B,Balkwill A,Cooper C,Roddam A,Brown A,Beral V,Million Women Study Collaborators.

    更新日期:2009-07-01 00:00:00

  • Abnormal regional cerebral blood flow on 99mTc ECD brain SPECT in patients with primary Sjögren's syndrome and normal findings on brain magnetic resonance imaging.

    abstract:OBJECTIVE:Technetium-99m ethyl cysteinate dimer (99mTc ECD) single photon emission computed tomography (SPECT) of the brain was used to detect abnormal regional cerebral blood flow (rCBF) in patients with primary Sjögren's syndrome (pSS) and normal findings on brain magnetic resonance imaging (MRI). METHODS:(99m)Tc EC...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.61.9.774

    authors: Chang CP,Shiau YC,Wang JJ,Ho ST,Kao A

    更新日期:2002-09-01 00:00:00

  • Clinical and radiological features of osteonecrosis in systemic lupus erythematosus.

    abstract::Symptomatic osteonecrosis occurred in 8 out of 68 patients with systemic lupus erythematosus. Multiple joints were involved in 3 patients, and weight-bearing joints were most frequently affected. Osteonecrosis tended to occur early in the disease, and the patients had all received corticosteroids. Symptoms tended to o...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.38.5.413

    authors: Griffiths ID,Maini RN,Scott JT

    更新日期:1979-10-01 00:00:00

  • Anti-TNF therapies and pregnancy: outcome of 130 pregnancies in the British Society for Rheumatology Biologics Register.

    abstract:OBJECTIVE:The British Society for Rheumatology Biologics Register (BSRBR) has collected data on adverse events including pregnancies in patients with rheumatoid arthritis treated with anti-tumour necrosis factor (anti-TNF) therapy. The purpose of this report is to summarise the pregnancy outcomes in women treated with ...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.2010.140822

    authors: Verstappen SM,King Y,Watson KD,Symmons DP,Hyrich KL,BSRBR Control Centre Consortium, BSR Biologics Register.

    更新日期:2011-05-01 00:00:00

  • IgA nephropathy associated with ankylosing spondylitis: occurrence in women as well as in men.

    abstract::Two patients (one male, one female) with ankylosing spondylitis (AS) and IgA nephropathy are described. The female patient is the first reported case to have AS and IgA nephropathy concurrently. Contrary to previously reported cases, her renal manifestation preceded her rheumatic symptoms. It is suggested that women w...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.48.5.435

    authors: Lai KN,Li PK,Hawkins B,Lai FM

    更新日期:1989-05-01 00:00:00

  • Shoulder-hand syndrome and symmetrical arthralgia in patients with tubo-ovarian carcinoma.

    abstract::Two cases of bilateral shoulder-hand syndrome and symmetrical arthralgia are described in patients with tubo-ovarian carcinoma. Swelling and contracture of the hands continued to develop despite oral corticosteroid therapy, and one patient underwent surgery in an attempt to prevent the development of further deformity...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.43.3.391

    authors: Taggart AJ,Iveson JM,Wright V

    更新日期:1984-06-01 00:00:00

  • The "X-Ray RheumaCoach" software: a novel tool for enhancing the efficacy and accelerating radiological quantification in rheumatoid arthritis.

    abstract:BACKGROUND:Precise diagnosis and follow up treatment of rheumatoid arthritis (RA) requires objective quantification, which is still lacking. For this purpose, radiological analyses are considered to be the most appropriate method. OBJECTIVE:To develop computer assisted quantification software that is particularly appl...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.62.6.579

    authors: Wick M,Peloschek P,Bögl K,Graninger W,Smolen JS,Kainberger F

    更新日期:2003-06-01 00:00:00

  • Munchausen's syndrome simulating reflex sympathetic dystrophy.

    abstract::A 15 year old girl who had pain, oedema of her left hand, and fever of four months' duration is described. Marked demineralisation of her hand was shown by radiography, and increased articular uptake by technetium-99m bone scan. All these changes were indistinguishable from reflex sympathetic dystrophy. After two admi...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.49.12.1010

    authors: Rodriguez-Moreno J,Ruiz-Martin JM,Mateo-Soria L,Rozadilla A,Roig-Escofet D

    更新日期:1990-12-01 00:00:00

  • Back to the future: forget ultrasound and focus on clinical assessment in rheumatoid arthritis management.

    abstract::Ultrasound (US) unquestionably improves many aspects of rheumatoid arthritis (RA) diagnosis and management, but no consensus has been reached regarding the optimal US methodology that should be used, and high levels of standardisation have not yet been attained. Current evidence from two randomised controlled trials d...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章,评审

    doi:10.1136/annrheumdis-2017-211458

    authors: Caporali R,Smolen JS

    更新日期:2018-01-01 00:00:00

  • Rasch analysis of the Western Ontario MacMaster questionnaire (WOMAC) in 2205 patients with osteoarthritis, rheumatoid arthritis, and fibromyalgia.

    abstract:OBJECTIVE:Advances in health measurement have led to the application of Rasch Item Response Theory (IRT) analysis (Rasch analysis) to evaluate instruments measuring health status and quality of life of patients, including the Health Assessment Questionnaire and SF-36. This study investigated the extent to which the Wes...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.58.9.563

    authors: Wolfe F,Kong SX

    更新日期:1999-09-01 00:00:00

  • Incidence and prevalence of juvenile arthritis in an urban population of southern Germany: a prospective study.

    abstract:OBJECTIVE:To ascertain the incidence and prevalence of juvenile arthritis in a German urban population. METHODS:All 766 paediatricians, orthopaedists, and rheumatologists working in practices or outpatient clinics in 12 south German towns were asked to report all patients who consulted them for juvenile arthritis duri...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.60.10.940

    authors: von Koskull S,Truckenbrodt H,Holle R,Hörmann A

    更新日期:2001-10-01 00:00:00

  • Incidences of overall and site specific cancers in TNFα inhibitor treated patients with rheumatoid arthritis and other arthritides - a follow-up study from the DANBIO Registry.

    abstract:OBJECTIVES:To investigate the incidence of cancer in arthritis patients treated with or without TNFα inhibitors (TNF-I). METHODS:Arthritis patients from the DANBIO database were followed-up for cancer in the Danish Cancer Registry during 2000-2008. RESULTS:Hazard ratio for cancer overall was 1.02 (95% confidence inte...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/annrheumdis-2012-201969

    authors: Dreyer L,Mellemkjær L,Andersen AR,Bennett P,Poulsen UE,Juulsgaard Ellingsen T,Hansen TH,Jensen DV,Linde L,Lindegaard HM,Loft AG,Nordin H,Omerovic E,Rasmussen C,Schlemmer A,Tarp U,Hetland ML

    更新日期:2013-01-01 00:00:00

  • Leishmaniasis in rheumatology, haematology and oncology: epidemiological, immunological and clinical aspects and caveats.

    abstract::Leishmaniasis is an intracellular protozoan infection that can lead to cutaneous, mucocutaneous, visceral or systemic manifestations depending on the parasite species and virulence and on the host immune response. It is endemic in countries of Europe (Mediterranean basin), Asia, Africa, Central and South America, but ...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章,评审

    doi:10.1136/annrheumdis-2011-200596

    authors: Bogdan C

    更新日期:2012-04-01 00:00:00

  • Characteristics of patients with antiphospholipid syndrome with major bleeding after oral anticoagulant treatment.

    abstract:OBJECTIVE:To study the demographic and clinical characteristics of patients with antiphospholipid syndrome (APS) with serious haemorrhagic complications of anticoagulant treatment in an attempt to establish risk factors for bleeding. METHODS:Patients with APS who were attending our lupus unit and who presented with se...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.60.5.527

    authors: Castellino G,Cuadrado MJ,Godfrey T,Khamashta MA,Hughes GR

    更新日期:2001-05-01 00:00:00

  • Prevalence of remission and its effect on damage and quality of life in Chinese patients with systemic lupus erythematosus.

    abstract:OBJECTIVES:To study the prevalence of remission and its effect on damage and quality of life (QOL) in Chinese patients with systemic lupus erythematosus (SLE). METHODS:Patients who fulfilled ≥4 American College of Rheumatology criteria for SLE were identified. Their remission status at last clinic visits was determine...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/annrheumdis-2016-210382

    authors: Mok CC,Ho LY,Tse SM,Chan KL

    更新日期:2017-08-01 00:00:00

  • Synovitis associated with serum IgM rheumatoid factor arising spontaneously in 'Old English' rabbits.

    abstract::This paper reports the spontaneous development of synovitis in 'Old English' rabbits concurrent with serum IgM rheumatoid factor. Female rabbits developed lesions at a higher incidence than males (42% compared with 17%) and the pathology was of a more severe nature. In the female rabbits synovitis was associated with ...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.45.4.331

    authors: Hanglow AC,Welsh CJ,Conn P,Thomas DS,Coombs RR

    更新日期:1986-04-01 00:00:00

  • Hard work never hurt anyone: or did it? A review of occupational associations with soft tissue musculoskeletal disorders of the neck and upper limb.

    abstract::Pain in the neck and upper limb is common and contributes considerably to absence from work due to sickness. Evidence suggest that prolonged abnormal posture and repetition contribute to such conditions. Psychosocial risk factors may also play a part in the aetiology of upper limb disorders. ...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章,收录出版,评审

    doi:10.1136/ard.2003.020016

    authors: Walker-Bone K,Cooper C

    更新日期:2005-10-01 00:00:00

  • Evaluating relationships between symptom duration and persistence of rheumatoid arthritis: does a window of opportunity exist? Results on the Leiden early arthritis clinic and ESPOIR cohorts.

    abstract:BACKGROUND:A prolonged symptom or disease duration at treatment initiation is associated with unfavourable outcomes in rheumatoid arthritis (RA). It is unknown whether this relation is linear, referring to a common 'the-earlier-the-better principle', or whether a transient time frame in which the disease is more suscep...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/annrheumdis-2014-206047

    authors: van Nies JA,Tsonaka R,Gaujoux-Viala C,Fautrel B,van der Helm-van Mil AH

    更新日期:2015-05-01 00:00:00

  • Polymyositis as a cause of total gut failure.

    abstract:BACKGROUND:Gastrointestinal manifestations are seen in systemic sclerosis and mixed connective tissue disorders but are rare in pure polymyositis. CASE REPORT:A 44 year old woman with polymyositis who developed total gut failure requiring treatment with total parenteral nutrition is described. RESULTS:The patient's p...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.61.4.305

    authors: Hughes AJ,Ferguson I,Rankin E,Kane K

    更新日期:2002-04-01 00:00:00

  • Interleukin 34 expression is associated with synovitis severity in rheumatoid arthritis patients.

    abstract:OBJECTIVES:Interleukin (IL) 34 is a new cytokine implicated in macrophage differentiation and osteoclastogenesis. This study assessed IL-34 expression in the tissue of patients with rheumatoid arthritis (RA). METHODS:Immunohistochemistry was performed in synovial biopsies from patients with RA (n=20), osteoarthritis (...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/annrheumdis-2011-200096

    authors: Chemel M,Le Goff B,Brion R,Cozic C,Berreur M,Amiaud J,Bougras G,Touchais S,Blanchard F,Heymann MF,Berthelot JM,Verrecchia F,Heymann D

    更新日期:2012-01-01 00:00:00

  • Mortality and risk factors of scleroderma renal crisis: a French retrospective study of 50 patients.

    abstract:OBJECTIVES:To describe presentation and outcome of patients with scleroderma renal crisis (SRC). METHODS:SRC was defined as rapidly progressive oliguric renal insufficiency and/or rapidly progressive arterial hypertension occurring during the course of systemic sclerosis (SSc). Chronic dialysis-free survival was analy...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章,多中心研究

    doi:10.1136/ard.2006.066985

    authors: Teixeira L,Mouthon L,Mahr A,Berezné A,Agard C,Mehrenberger M,Noël LH,Trolliet P,Frances C,Cabane J,Guillevin L,Group Français de Recherche sur le Sclérodermie (GFRS).

    更新日期:2008-01-01 00:00:00

  • Successful reintroduction of methotrexate after pneumonitis in two patients with rheumatoid arthritis.

    abstract::Two patients are described with severe and progressive rheumatoid arthritis in whom methotrexate was reintroduced despite previous methotrexate related pneumonitis. In both patients a marked improvement in disease control occurred without a recurrence of the pneumonitis. ...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.51.2.272

    authors: Cook NJ,Carroll GJ

    更新日期:1992-02-01 00:00:00

  • Thermal stability and structure of cancellous bone mineral from the femoral head of patients with osteoarthritis or osteoporosis.

    abstract:BACKGROUND:Cancellous bone from patients with osteoarthritis (OA) has been reported to be undermineralised and that from patients with osteoporosis (OP) is more liable to fracture. Changes in the mineral component might be implicated in these processes. OBJECTIVES:To investigate the thermal stability and the mineral s...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章

    doi:10.1136/ard.2004.021329

    authors: Mkukuma LD,Imrie CT,Skakle JM,Hukins DW,Aspden RM

    更新日期:2005-02-01 00:00:00

  • Long-term safety of pegloticase in chronic gout refractory to conventional treatment.

    abstract:OBJECTIVE:To evaluate the long-term safety (up to 3 years) of treatment with pegloticase in patients with refractory chronic gout. METHODS:This open-label extension (OLE) study was conducted at 46 sites in the USA, Canada and Mexico. Patients completing either of two replicate randomised placebo-controlled 6-month tri...

    journal_title:Annals of the rheumatic diseases

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1136/annrheumdis-2012-201795

    authors: Becker MA,Baraf HS,Yood RA,Dillon A,Vázquez-Mellado J,Ottery FD,Khanna D,Sundy JS

    更新日期:2013-09-01 00:00:00