title: Strategies to predict rheumatoid arthritis development in at-risk populations.
abstract: The development of RA is conceived as a multiple hit process and the more hits that are acquired, the greater the risk of developing clinically apparent RA. Several at-risk phases have been described, including the presence of genetic and environmental factors, RA-related autoantibodies and biomarkers and symptoms. Intervention in these preclinical phases may be more effective compared with intervention in the clinical phase. One prerequisite for preventive strategies is the ability to estimate an individual's risk adequately. This review evaluates the ability to predict the risk of RA in the various preclinical stages. Present data suggest that a combination of genetic and environmental factors is helpful to identify persons at high risk of RA among first-degree relatives. Furthermore, a combination of symptoms, antibody characteristics and environmental factors has been shown to be relevant for risk prediction in seropositive arthralgia patients. Large prospective studies are needed to validate and improve risk prediction in preclinical disease stages.
authors.affiliation: Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA, d.v.schaardenburg@reade.nl.
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Karlson
authors.affiliation: Jan van Breemen Research Institute | Reade, Amsterdam and d.v.schaardenburg@reade.nl.
authors.forename: Dirkjan
authors.initials: D
authors.lastname: van Schaardenburg
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Annette H
authors.initials: AH
authors.lastname: van der Helm-van Mil
mesh_terms: D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D014943:Global Health; D006801:Humans; D009017:Morbidity; D017410:Practice Guidelines as Topic; D012307:Risk Factors
chemical_list: D001323:Autoantibodies
keywords: (genetic) risk; ACPA; arthralgia; autoantibodies; epidemiology; preclinical; prediction; rheumatoid arthritis
references.citation: Ann Rheum Dis. 2013 Dec;72(12):1920-6
references.pmid: 23178208
references.citation: Arthritis Rheum. 2010 Nov;62(11):3161-72
references.pmid: 20597112
references.citation: J Rheumatol. 1991 Sep;18(9):1282-4
references.pmid: 1757925
references.citation: Arthritis Rheum. 2013 Nov;65(11):2773-82
references.pmid: 23897126
references.citation: Ann Rheum Dis. 2014 Jun;73(6):1277-9
references.pmid: 24419332
references.citation: Ann Rheum Dis. 2013 Aug;72(8):1302-7
references.pmid: 22956597
references.citation: Arthritis Rheum. 2010 Mar;62(3):694-704
references.pmid: 20131234
references.citation: Ann Rheum Dis. 2011 Mar;70(3):508-11
references.pmid: 21149499
references.citation: Arthritis Rheum. 2013 Apr;65(4):899-910
references.pmid: 23310951
references.citation: Am J Med. 2002 Apr 15;112(6):465-71
references.pmid: 11959057
references.citation: Arthritis Care Res (Hoboken). 2013 Jul;65(7):1147-56
references.pmid: 23495093
references.citation: Nat Genet. 2012 Jan 29;44(3):291-6
references.pmid: 22286218
references.citation: Arthritis Rheum. 2011 Mar;63(3):633-9
references.pmid: 21360492
references.citation: Ann Rheum Dis. 2015 Aug;74(8):1522-9
references.pmid: 24685909
references.citation: Arthritis Rheum. 2000 Jan;43(1):155-63
references.pmid: 10643712
references.citation: Arthritis Rheum. 1987 Nov;30(11):1205-13
references.pmid: 2446635
references.citation: Ann Rheum Dis. 2010 Jan;69(1):54-60
references.pmid: 19151010
references.citation: Stat Med. 2012 Jan 30;31(2):101-13
references.pmid: 22147389
references.citation: Ann Rheum Dis. 2006 Apr;65(4):535-7
references.pmid: 16079166
references.citation: Nat Rev Genet. 2009 Apr;10(4):264-9
references.pmid: 19238176
references.citation: Nat Genet. 2012 Dec;44(12):1336-40
references.pmid: 23143596
references.citation: Rheumatology (Oxford). 2014 Sep;53(9):1646-53
references.pmid: 24729397
references.citation: Ann Rheum Dis. 2010 Mar;69(3):571-4
references.pmid: 19363022
references.citation: J Rheumatol. 2009 Jun;36(6):1130-5
references.pmid: 19411392
references.citation: Ann Rheum Dis. 2013 Jun;72(6):901-7
references.pmid: 22915618
references.citation: Rheumatology (Oxford). 2011 Jan;50(1):93-100
references.pmid: 20639266
references.citation: Ann Rheum Dis. 2013 May;72(5):776-80
references.pmid: 23434571
references.citation: Stat Med. 2008 Jan 30;27(2):157-72; discussion 207-12
references.pmid: 17569110
references.citation: Ann Rheum Dis. 2015 Sep;74(9):1659-66
references.pmid: 24728331
references.citation: Am J Med. 2006 Jun;119(6):503.e1-9
references.pmid: 16750964
references.citation: Arthritis Rheumatol. 2014 May;66(5):1133-40
references.pmid: 24782178
references.citation: Ann Rheum Dis. 2015 Jan;74(1):170-6
references.pmid: 24092415
references.citation: PLoS One. 2012;7(5):e35296
references.pmid: 22662108
references.citation: Arthritis Rheum. 2009 Dec 15;61(12):1735-42
references.pmid: 19950324
references.citation: Ann Rheum Dis. 2015 Jun;74(6):1225-32
references.pmid: 24718962
references.citation: Rheum Dis Clin North Am. 2012 May;38(2):405-26
references.pmid: 22819092
references.citation: Ann Rheum Dis. 2013 Jan;72(1):13-22
references.pmid: 22532640
references.citation: Arthritis Rheum. 2003 Oct;48(10):2741-9
references.pmid: 14558078
references.citation: Ann Rheum Dis. 2007 Feb;66(2):267-9
references.pmid: 16868018
references.citation: Nature. 2014 Feb 20;506(7488):376-81
references.pmid: 24390342
references.citation: Ann Rheum Dis. 2012 May;71(5):638-41
references.pmid: 22387728
references.citation: Arthritis Rheum. 2012 May;64(5):1323-8
references.pmid: 22130974
references.citation: Ann Rheum Dis. 2010 Jan;69(1):70-81
references.pmid: 19174392
references.citation: Br J Rheumatol. 1993 Oct;32(10):903-7
references.pmid: 8402000
references.citation: Arthritis Rheum. 2009 Mar;60(3):661-8
references.pmid: 19248111
references.citation: Ann Rheum Dis. 2013 Aug;72(8):1295-301
references.pmid: 22952388
references.citation: Arthritis Rheum. 2009 Mar;60(3):641-52
references.pmid: 19248103
references.citation: J Clin Invest. 2006 Apr;116(4):961-73
references.pmid: 16585962
references.citation: Ann Rheum Dis. 2007 Jan;66(1):121-3
references.pmid: 16740681
references.citation: PLoS Genet. 2013;9(9):e1003808
references.pmid: 24068971
references.citation: Arthritis Rheum. 2010 Sep;62(9):2633-9
references.pmid: 20496417
references.citation: Arthritis Rheum. 2010 Dec;62(12):3560-8
references.pmid: 20722010
references.citation: Arthritis Rheum. 2004 Aug;50(8):2423-7
references.pmid: 15334453
references.citation: Arthritis Rheum. 2012 Jun;64(6):1720-9
references.pmid: 22354869
references.citation: Arthritis Rheum. 2004 Feb;50(2):380-6
references.pmid: 14872479
references.citation: Ann Rheum Dis. 2008 Jun;67(6):860-6
references.pmid: 17644543
references.citation: Arthritis Rheum. 2006 Jan;54(1):38-46
references.pmid: 16385494
references.citation: Arthritis Rheum. 1992 Aug;35(8):914-7
references.pmid: 1379430
references.citation: Ann Rheum Dis. 2010 Mar;69(3):490-4
references.pmid: 19363023
references.citation: Ann Rheum Dis. 2012 Mar;71(3):363-8
references.pmid: 21989539
references.citation: J Rheumatol. 2010 Jun;37(6):1105-12
references.pmid: 20436074
references.citation: Arthritis Rheum. 2011 Nov;63(11):3226-33
references.pmid: 21792832
references.citation: Arthritis Rheum. 2013 Aug;65(8):1995-2004
references.pmid: 23754702
references.citation: Ann Rheum Dis. 2013 Oct;72(10):1654-8
references.pmid: 23104761
references.citation: Ann Rheum Dis. 2015 Jan;74(1):234-41
references.pmid: 24106048
references.citation: Arthritis Rheum. 2010 Feb;62(2):383-91
references.pmid: 20112361
references.citation: Ann Rheum Dis. 2012 Jun;71(6):825-9
references.pmid: 22128080
references.citation: Ann Rheum Dis. 2014 Apr;73(4):780-3
references.pmid: 24336334
references.citation: Rheumatology (Oxford). 2012 Mar;51(3):499-512
references.pmid: 22120459
references.citation: Ann Rheum Dis. 2010 Jun;69(6):1077-85
references.pmid: 20233754
references.citation: Ann Rheum Dis. 2006 Sep;65(9):1163-7
references.pmid: 16887863
references.citation: Stat Med. 2011 Jan 15;30(1):11-21
references.pmid: 21204120
references.citation: J Rheumatol. 2012 Dec;39(12):2253-60
references.pmid: 23070994
references.citation: Stat Med. 1997 May 15;16(9):965-80
references.pmid: 9160492
references.citation: J Rheumatol. 2013 Sep;40(9):1523-8
references.pmid: 23908443
references.citation: Arthritis Rheum. 2009 Dec 15;61(12):1642-9
references.pmid: 19950306
references.citation: Arthritis Rheum. 2008 Nov 15;59(11):1589-95
references.pmid: 18975365
references.citation: Arthritis Res Ther. 2013 Oct 23;15(5):R159
references.pmid: 24286474
references.citation: J Clin Invest. 1998 Jan 1;101(1):273-81
references.pmid: 9421490
references.citation: Br J Rheumatol. 1992 Jun;31(6):365-8
references.pmid: 1596697
references.citation: Am J Hum Genet. 2011 Jan 7;88(1):57-69
references.pmid: 21211616