A comparative study of IgG second- and third-generation anti-cyclic citrullinated peptide (CCP) ELISAs and their combination with IgA third-generation CCP ELISA for the diagnosis of rheumatoid arthritis.
To compare IgG anti-cyclic citrullinated peptide (CCP) enzyme-linked immunosorbent assays (ELISAs) of second (anti-CCP2) and third generations (anti-CCP3) for the diagnosis of rheumatoid arthritis (RA), an IgA CCP3 ELISA was also evaluated. Combinations of the use of the three tests were evaluated. Anti-CCP2 IgG, anti-CCP3 IgG, and anti-CCP3 IgA antibody levels were determined by ELISAs in the serum of 70 patients with rheumatoid arthritis, 34 patients with systemic lupus erythematosus (SLE), and 54 normal subjects. We evaluated the serum levels, diagnostic performance, and the use of a combination of tests for RA diagnosis. Statistical analyses include receiver operating curves (ROCs) and others. The serum levels were higher in RA patients. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio (LR), and negative LR were, respectively, 78.6%, 94.3%, 91.7%, 84.7%, 13.8, and 0.23 for anti- CCP2 IgG and 82.9%, 93.2%, 90.6%, 87.2%, 12.2, and 0.18 for anti-CCP3 IgG. These values were better than the same statistical tests for anti-CCP3 IgA. ROC analysis showed that anti-CCP2 IgG and anti-CCP3 IgG had good performance and similar areas. Measuring both IgG and IgA anti-CCP tests increases the specificity if both tests were positive and increases the sensitivity if either test were positive. In our population, anti-CCP2 IgG and anti-CCP3 IgG had good diagnostic performance. Anti-CCP3 IgG had 4.3% more sensitivity than the anti-CCP2 IgG test while sustaining high specificity. This and other studies suggest the development of a dual test--CCP3 IgG and IgA that may be a potential diagnostic tool.
dos Anjos
Lisiane Maria Enriconi
LM
Universidade do Sul de Santa Catarina (UNISUL), Tubarao, Brazil.
Pereira
Ivanio Alves
IA
d 'Orsi
Eleonora
E
Seaman
Andrea Piette
AP
Burlingame
Rufus Watson
RW
Morato
Edelton Flavio
EF
D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D001938:Brazil; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D011237:Predictive Value of Tests; D012372:ROC Curve; D012680:Sensitivity and Specificity
D000888:Antibodies, Anti-Idiotypic; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide
Arthritis Rheum. 2004 Mar;50(3):709-15
15022309
Arthritis Res. 2002;4(2):87-93
11879544
J Immunol. 1999 Jan 1;162(1):585-94
9886436
Autoimmun Rev. 2005 Jul;4(6):389-94
16081030
Clin Rheumatol. 2008 Jan;27(1):77-83
17570008
N Z Med J. 2004 Oct 08;117(1203):U1097
15477921
J Clin Invest. 1995 Jun;95(6):2672-9
7539459
Arthritis Res. 2002;4 Suppl 2:S1-5
12110150
J Rheumatol. 2003 Dec;30(12):2535-9
14719190
Pathol Biol (Paris). 2005 Mar;53(2):63-7
15708648
Arthritis Rheum. 2000 Jan;43(1):155-63
10643712
Arthritis Res Ther. 2004;6(4):R303-8
15225365
Ann Rheum Dis. 1964 Jul;23:302-5
14178016
Ann Rheum Dis. 2004 Dec;63(12):1587-93
15547083
Ann Rheum Dis. 1981 Jun;40(3):263-6
6166255
Ann Rheum Dis. 2004 Sep;63(9):1079-84
15308516
Ann Rheum Dis. 2006 Jul;65(7):845-51
16606649
Clin Exp Rheumatol. 2007 Jan-Feb;25(1):47-53
17417990
Clin Rheumatol. 2007 Nov;26(11):1883-9
17410320
Ann N Y Acad Sci. 2005 Jun;1050:314-8
16014547
Clin Exp Rheumatol. 1999 Nov-Dec;17(6):689-97
10609067
Ann Intern Med. 2007 Jun 5;146(11):797-808
17548411
Arthritis Rheum. 2004 Feb;50(2):380-6
14872479
Eur Ann Allergy Clin Immunol. 2004 Apr;36(4):127-30
15180353
Ann Rheum Dis. 2005 Oct;64(10):1510-2
15800005
Arthritis Rheum. 2002 Feb;46(2):328-46
11840435
Arthritis Rheum. 1997 Sep;40(9):1725
9324032
Br Med J. 1979 Jul 14;2(6182):97-9
111762
Arthritis Rheum. 2006 Dec;54(12):3799-808
17133560
Ann Rheum Dis. 2005 Dec;64(12):1744-9
15843452
Arthritis Rheum. 1996 May;39(5):713-22
8639167
Clin Rev Allergy Immunol. 2007 Feb;32(1):47-56
17426360
J Rheumatol. 1998 May;25(5):838-46
9598877
Clin Exp Immunol. 2004 Jan;135(1):173-80
14678280
J Clin Invest. 1998 Jan 1;101(1):273-81
9421490
Rinsho Byori. 2004 Dec;52(12):966-72
15675342
Joint Bone Spine. 2001 Mar;68(2):103-5
11324923