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Specific Autoantibodies Precede The Symptoms Of Rheumatoid Arthritis: A Study Of Serial Measurements In Blood Donors.

M. Nielen, D. van Schaardenburg, H. Reesink, R. J. van de Stadt, I. E. van der Horst-Bruinsma, M. de Koning, M. Habibuw, J. Vandenbroucke, B. Dijkmans
Published 2004 · Medicine

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OBJECTIVE Autoantibodies have been demonstrated in single serum samples from healthy subjects up to 10 years before they developed rheumatoid arthritis (RA). However, the time course for the development of antibodies before onset of clinical RA is unknown, nor is it known which antibody, or combinations of antibodies, might be most sensitive or specific for predicting future development of the disease. The present study was undertaken to investigate this. METHODS Patients with RA who had been blood donors before the onset of disease symptoms were enrolled. Frozen serum samples from each donor were retrieved, together with 2 serum samples from controls matched for age, sex, and date of donation. All samples were tested for IgM rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies. RESULTS Seventy-nine patients with RA (62% female; mean age at onset of symptoms 51 years) were included. A median of 13 samples (range 1-51) per patient were available; the earliest samples had been collected a median of 7.5 years (range 0.1-14.5) before the onset of symptoms. Thirty-nine patients (49%) were positive for IgM-RF and/or anti-CCP on at least one occasion before the development of RA symptoms, a median of 4.5 years (range 0.1-13.8) before symptom onset. Of the 2,138 control samples, 1.1% were positive for IgM-RF, and 0.6% were positive for anti-CCP. CONCLUSION Approximately half of patients with RA have specific serologic abnormalities several years before the onset of symptoms. A finding of an elevated serum level of IgM-RF or anti-CCP in a healthy individual implies a high risk for the development of RA. We conclude that IgM-RF and anti-CCP testing with appropriately high specificity may assist in the early detection of RA in high-risk populations.
This paper references
10.1136/ard.44.8.519
Association of MHC antigens with susceptibility to and severity of rheumatoid arthritis in multicase families.
D. Walker (1985)
Rheumatoid factors antedating clinical rheumatoid arthritis.
K. Aho (1991)
10.1006/JAUT.1996.0096
Cyclosporine delays but does not prevent clinical onset in glucose intolerant pre-type 1 diabetic children.
J. Carel (1996)
Effects of insulin in relatives of patients with type 1 diabetes mellitus
DJ Walker (2002)
10.1093/RHEUMATOLOGY/31.6.365
Incidence of rheumatoid arthritis in a genetically predisposed population.
A. Silman (1992)
10.1002/ART.1780350810
Immunopathology of rheumatoid arthritis
P. Kurki (1992)
Reuma in Nederland: de cijfers; Actualisering 2000
A. Chorus (2001)
10.1093/RHEUMATOLOGY/39.7.742
Levels of markers of bone resorption are moderately increased in patients with inactive rheumatoid arthritis.
E. Molenaar (2000)
10.1016/S0140-6736(87)91672-2
LONG-TERM OUTCOME OF TREATING RHEUMATOID ARTHRITIS: RESULTS AFTER 20 YEARS
D. Scott (1987)
10.1002/1529-0131(199808)41:8<1481::AID-ART19>3.0.CO;2-O
Asymptomatic synovitis precedes clinically manifest arthritis.
M. Kraan (1998)
10.1136/ard.46.9.674
Standardisation of serological tests for rheumatoid factor measurement.
F. Klein (1987)
10.1002/1529-0131(200001)43:1<155::AID-ANR20>3.0.CO;2-3
The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide.
G. A. Schellekens (2000)
10.1016/S0140-6736(98)08513-4
Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial
T. Möttönen (1999)
10.1136/ard.59.2.149
A prospective study on the incidence of rheumatoid arthritis among people with persistent increase of rheumatoid factor
H. Halldórsdóttir (2000)
10.1172/JCI1316
Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies.
G. A. Schellekens (1998)
10.1002/1529-0131(200009)43:9<1927::AID-ANR3>3.0.CO;2-B
The course of radiologic damage during the first six years of rheumatoid arthritis.
H. Hulsmans (2000)
10.1016/S0140-6736(97)01300-7
Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis
M. Boers (1997)
Immunopathology of rheumatoid arthritis. Antikeratin antibodies precede the clinical disease.
P. Kurki (1992)
10.1136/ard.59.6.468
Aggressive treatment in early rheumatoid arthritis: a randomised controlled trial
C. H. van Jaarsveld (2000)
10.1002/ART.1780310302
The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.
F. Arnett (1988)
Rheumatoid factor and antibodies to cyclic citrullinated Peptide differentiate rheumatoid arthritis from undifferentiated polyarthritis in patients with early arthritis.
A. Jansen (2002)
10.1016/S0140-6736(94)92521-6
Antibodies to glutamic acid decarboxylase as predictors of insulin-dependent diabetes mellitus before clinical onset of disease
J. Tuomilehto (1994)
Effects of insulin in relatives of patients with type 1 diabetes mellitus
Jay S. Skyler (2002)
10.1136/ard.45.8.684
Rheumatoid factor tests in the diagnosis and prediction of rheumatoid arthritis.
D. Walker (1986)
10.1002/ART.1780270805
Severe functional declines, work disability, and increased mortality in seventy-five rheumatoid arthritis patients studied over nine years.
T. Pincus (1984)
10.4081/reumatismo.2001.156
Use of antikeratin antibodies to distinguish between rheumatoid arthritis and polyarthritis associated with hepatitis C infection.
A. Kessel (2000)
10.1002/1529-0131(200106)44:6<1248::AID-ART215>3.0.CO;2-8
Time to first occurrence of erosions in inflammatory polyarthritis: results from a prospective community-based study.
M. Bukhari (2001)
10.1002/ART.1780311004
The incidence of rheumatoid arthritis is predicted by rheumatoid factor titer in a longitudinal population study.
A. del Puente (1988)
Antinuclear antibodies heralding the onset of systemic lupus erythematosus.
K. Aho (1992)
10.1002/1529-0131(200108)44:8<1736::AID-ART308>3.0.CO;2-I
Prognostic factors for radiographic damage in early rheumatoid arthritis: a multiparameter prospective study.
B. Combe (2001)
10.1186/AR93
Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset
R. Goldbach-Mansky (2000)
10.1097/00006416-199003000-00011
Revised criteria for the classification of rheumatoid arthritis.
F. Arnett (1990)



This paper is referenced by
10.1002/art.33489
Avidity maturation of anti-citrullinated protein antibodies in rheumatoid arthritis.
P. Suwannalai (2012)
10.1002/art.33472
Increased frequency of complement C4B deficiency in rheumatoid arthritis.
W. Rigby (2012)
10.1136/postgradmedj-2011-130364
A B cell explanation for autoimmune disease: the forbidden clone returns
F. McQueen (2012)
10.1093/qjmed/hcu008
The risk of asthma in rheumatoid arthritis: a population-based cohort study.
T-C. Shen (2014)
10.3109/03009742.2012.723744
Smoking, low formal level of education, alcohol consumption, and the risk of rheumatoid arthritis
U. Bergström (2013)
10.1016/j.clim.2012.10.005
The role of B lymphocytes in the progression from autoimmunity to autoimmune disease.
G. Salinas (2013)
10.5772/20908
Validation of Protein Biomarkers to Advance the Management of Autoimmune Disorders
David Gibson (2011)
Somatic mutations in autoimmunity
P. Savola (2019)
The predictive significance of autoantibodies in autoimmune diseases
M. Cojocaru (2008)
10.3389/fimmu.2018.02352
Rheumatoid Arthritis-Associated Autoimmunity Due to Aggregatibacter actinomycetemcomitans and Its Resolution With Antibiotic Therapy
Amarshi Mukherjee (2018)
10.1093/rheumatology/kex506
Can an increase in autoantibody levels predict arthritis in arthralgia patients?
Marian H. van Beers-Tas (2018)
10.1016/J.RCREUE.2019.01.001
Interpretation of autoantibodies in rheumatological diseases
Tatiana Méndez-Rayo (2018)
10.1038/s41405-020-0034-8
Temporomandibular joint function, periodontal health, and oral microbiome in early rheumatoid arthritis and at-risk individuals: a prospective cohort study protocol
J. M. Kroese (2020)
10.1111/imr.12842
Lung inflammation in the pathogenesis of rheumatoid arthritis
M. K. Demoruelle (2020)
10.1093/rheumatology/kex340
The risk of individual autoantibodies, autoantibody combinations and levels for arthritis development in clinically suspect arthralgia
R. M. ten Brinck (2017)
10.1016/j.clinthera.2019.04.034
Understanding and Prevention of the Evolution Toward Autoimmune Rheumatoid Arthritis: The New Challenge.
L. Klareskog (2019)
10.1186/s13075-015-0638-x
Associations of antibodies against citrullinated peptides with human leukocyte antigen-shared epitope and smoking prior to the development of rheumatoid arthritis
H. Kokkonen (2015)
10.2174/1874312901206010303
The Effect of Stopping Smoking on Disease Activity in Rheumatoid Arthritis (RA). Data from BARFOT, a Multicenter Study of Early RA
M. Andersson (2012)
Autoantibodies and genetic variation in rheumatoid arthritis
A. Kastbom (2007)
Clinical and molecular characterization of the type I interferon signature in rheumatic diseases
Theunis De Jong (2016)
10.1038/ncomms15869
Somatic mutations in clonally expanded cytotoxic T lymphocytes in patients with newly diagnosed rheumatoid arthritis
P. Savola (2017)
Window of opportunity.
D. Furst (2004)
10.1038/s41598-019-48176-3
Citrullination facilitates cross-reactivity of rheumatoid factor with non-IgG1 Fc epitopes in rheumatoid arthritis
M. Trela (2019)
10.1007/s10875-012-9841-6
Anti-citrullinated Protein Antibodies Activated ERK1/2 and JNK Mitogen-activated Protein Kinases via Binding to Surface-expressed Citrullinated GRP78 on Mononuclear Cells
Ming-Chi Lu (2012)
10.1515/CCLM.2010.152
Diagnostic performance of anti-citrullinated peptide antibodies for the diagnosis of rheumatoid arthritis: the relevance of likelihood ratios
D. Pietrapertosa (2010)
Novel Roles for Arginine Modifying Enzymes in Immune Regulation
Saskia Hemmers (2010)
Autoimmune Responses in the Rheumatoid
M. Toes (2009)
10.2217/pmt.16.4
Pain in rheumatoid arthritis: models and mechanisms.
D. Baş (2016)
10.1136/annrheumdis-2013-204543
IgM rheumatoid factor amplifies the inflammatory response of macrophages induced by the rheumatoid arthritis-specific immune complexes containing anticitrullinated protein antibodies
L. Laurent (2015)
10.1016/j.jprot.2016.03.031
Comparative analysis of novel autoantibody isotypes against citrullinated-inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3)(542-556) peptide in serum from Taiwanese females with rheumatoid arthritis, primary Sjögren's syndrome and secondary Sjögren's syndrome in rheumatoid arthritis.
C. Liao (2016)
10.1136/annrheumdis-2012-202349
Autoimmunity in rheumatoid arthritis: different antigens—common principles
L. Trouw (2013)
Targeting human synovium using homing peptides identified by in vivo phage display
T. Garrood (2009)
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