Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis
V P K Nell, K P Machold, T A Stamm, G Eberl, H Heinzl, M Uffmann, J S Smolen, G Steiner, V P K Nell, K P Machold, T A Stamm, G Eberl, H Heinzl, M Uffmann, J S Smolen, G Steiner
Abstract
Background: Early treatment prevents progression of joint damage in rheumatoid arthritis (RA), but diagnosis in early disease is impeded by lack of appropriate diagnostic criteria.
Objective: To study the value of rheumatoid factor (RF), anti-cyclic citrullinated peptide autoantibodies (anti-CCP), and anti-RA33 autoantibodies for diagnosis of RA and prediction of outcome in patients with very early arthritis.
Methods: The prospective follow up inception cohort included 200 patients with very early (<3 months) inflammatory joint disease. Autoantibodies were measured at baseline and analysed in a tree based model which aimed at determining the added diagnostic value of testing for anti-CCP and anti-RA33 as compared with RF alone.
Results: RA was diagnosed in 102 patients, while 98 developed other inflammatory arthropathies. Receiver operator curve analysis showed an optimum cut off level for RF at 50 U/ml, above which anti-CCP and anti-RA33 had no additional diagnostic value. Remarkably, RF >or=50 U/ml and anti-CCP showed similar sensitivity and high specificity for RA, but overlapped considerably. Anti-RA33 was less specific and did not correlate with RF or anti-CCP. Among patients with RA, 72% showed at least one of these three autoantibodies, compared with 15% of non-RA patients. RF >or=50 U/ml and anti-CCP were predictors of erosive disease, whereas anti-RA33 was associated with mild disease.
Conclusions: Stepwise autoantibody testing in early inflammatory joint disease, starting with RF, followed by anti-CCP (in patients with RF <50 U/ml), and finally anti-RA33, should be used as a sensitive and effective strategy for distinguishing patients with RA at high risk for poor outcome.
Figures
References
- J Rheumatol. 2000 Jan;27(1):264-8
- Ann Rheum Dis. 2005 Aug;64(8):1199-204
- J Immunol. 2002 Jul 15;169(2):1068-76
- Arthritis Res. 2002;4 Suppl 2:S1-5
- J Rheumatol. 2002 Oct;29(10):2074-6
- J Rheumatol. 2002 Nov;29(11):2278-87
- Ann Rheum Dis. 2003 Feb;62(2):120-6
- Ann Clin Biochem. 2003 Mar;40(Pt 2):131-7
- J Rheumatol. 2003 May;30(5):902-4
- Arthritis Rheum. 2003 Oct;48(10):2741-9
- Ann Rheum Dis. 2004 Mar;63(3):274-9
- Clin Exp Rheumatol. 2003 Sep-Oct;21(5 Suppl 31):S113-7
- Clin Exp Rheumatol. 2003 Sep-Oct;21(5 Suppl 31):S154-7
- Arthritis Rheum. 2004 Mar;50(3):709-15
- Arthritis Res Ther. 2004;6(2):R142-50
- N Engl J Med. 2004 Jun 17;350(25):2591-602
- Rheumatology (Oxford). 2004 Jul;43(7):906-14
- Scand J Rheumatol. 2004;33(3):185-8
- Lancet. 2004 Jul 17-23;364(9430):263-9
- Ann Rheum Dis. 2004 Sep;63(9):1085-9
- Ann Rheum Dis. 2004 Sep;63(9):1090-5
- Acta Radiol Diagn (Stockh). 1977 Jul;18(4):481-91
- Lancet. 1987 May 16;1(8542):1108-11
- Arthritis Rheum. 1988 Mar;31(3):315-24
- BMJ. 1990 Jan 27;300(6719):230-5
- Br J Rheumatol. 1992 Apr;31(4):219-20
- Clin Chem. 1993 Apr;39(4):561-77
- J Rheumatol. 1993 Aug;20(8):1278-81
- Clin Exp Rheumatol. 1993 Nov-Dec;11(6):645-7
- J Clin Invest. 1995 Jun;95(6):2672-9
- Ann Intern Med. 1996 Apr 15;124(8):699-707
- J Clin Invest. 1997 Jul 1;100(1):127-35
- J Clin Invest. 1998 Jan 1;101(1):273-81
- J Rheumatol Suppl. 1998 Jul;53:13-9
- J Rheumatol. 1998 Dec;25(12):2324-30
- Lancet. 1999 May 8;353(9164):1568-73
- Arthritis Rheum. 1999 Oct;42(10):2184-8
- Best Pract Res Clin Rheumatol. 2005 Feb;19(1):163-77
- J Rheumatol. 2005 Feb;32(2):231-8
- Ann Rheum Dis. 2002 Jul;61(7):630-4
Source: PubMed