한국인 류마티스관절염 환자에서 항CCP항체와 류마티스인자의 진단정확성에 대한 메타분석연구 = Diagnostic Accuracies of Anti-cyclic Citrullinated Peptide Antibody and Rheumatoid Factor in Korean Patients with Rheumatoid Arthritis: A Meta-analysis

국문 초록 (Abstract)

목적: 한국인 류마티스관절염 환자에서 항CCP항체와 류마티스인자의 민감도와 특이도, 진단정확성에 대해 연구하였다. 방법: 문헌검색은 Medline과 Koreamed, 대한류마티스학회지를 이용하였고 논문들의 참고문헌도 조사하였다. Random-effects 모델을 이용하여 메타분석을 시행하였으며 항CCP항체와 류마티스인자의 민감도, 특이도, positive와 negative likelihood ratios (PLR, NLR), diagnostic odds ratio (DOR)와 summary receiver-operating characteristic curve (SROC 커브)를 구하였다. 결과: 항CCP항체와 류마티스인자의 민감도와 특이도를 연구한 7개의 논문의 류마티스관절염환자 1,041명과 대조군 970명이 메타분석에 포함되었다. 항CCP항체의 민감도와 특이도, PLR, NLR, DOR은 76.7% (95% confidence interval [CI] 74.0∼79.2), 95.1% (93.8∼96.3), 14.837 (11.567∼19.031), 0.244 (0.202∼0.294)과 59.235 (43.806∼80.097)이었고 류마티스인자의 수치는 78.2% (0.756∼0.807), 80.5% (78.1∼82,6), 3.687 (3.027∼4.492), 0.298 (0.218∼0.406)과 12.915 (8.427∼19.771)이었다. 항CCP항체의 area under the curve (AUC)와 Q* index는 0.9453과 0.8842이었고 류마티스인자의 수치들은 0,8583과 0.7891이었다. 항CCP항체는 류마티스인자와 비교하여 특이도와 PLR, DOR, AUC, Q* index가 높았으며 민감도와 NLR은 유사하였다. 항CCP항체와 류마티스인자가 모두 양성인 경우 특이도와 AUC가 류마티스인자에 비해 현저히 증가하였다(특이도 96.5% vs. 80.5%, AUC 0.9864 vs. 0.8583). 결론: 한국인에서 항CCP항체는 류마티스인자와 비슷한 민감도를 보이나 특이도와 진단 정확성은 더 높았고 항CCP항체와 류마티스인자를 같이 검사하는 경우 항CCP항체나 류마티스인자보다 진단정확성이 증가하여 한국인 류마티스관절염 진단에 유용할 것으로 보인다.

참고문헌 (Reference)

1 박성훈, "한국인 조기 류마티스관절염에서 항CCP항체의 진단적 의의" 대한류마티스학회 14 (14): 227-234, 2007

2 강희정, "류마티스 관절염에서 항Cyclic Citrullinated Peptide 항체의 진단적 유용성" 대한류마티스학회 10 (10): 117-125, 2003

3 Masson-Bessiere, C., "The major synovial targets of the rheumatoid arthritisspecific antifilaggrin autoantibodies are deiminated forms of the alpha- and beta-chains of fibrin" 166 : 4177-4184, 2001

4 Schellekens, G.A., "The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide" 43 : 155-163, 2000

5 Glas, A.S., "The diagnostic odds ratio: a single indicator of test performance" 56 : 1129-1135, 2003

6 Arnett, F.C., "The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis" 31 : 315-324, 1988

7 Nielen, M.M., "Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors" 50 : 380-386, 2004

8 Dorner, T., "Rheumatoid factor revisited" 16 : 246-253, 2004

9 Lee, D.M., "Rheumatoid arthritis" 358 : 903-911, 2001

10 Higgins, J.P., "Quantifying heterogeneity in a meta-analysis" 21 : 1539-1558, 2002

11 Walter, S.D., "Properties of the summary receiver operating characteristic (SROC) curve for diagnostic test data" 21 : 1237-1256, 2002

12 Lee, Y.H., "PADI4 polymorphisms and rheumatoid arthritis susceptibility: a meta-analysis" 27 : 827-833, 2007

13 Vossenaar, E.R., "PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease" 25 : 1106-1118, 2003

14 Egger, M., "Meta-analysis: principles and procedures" 3157 : 1533-1537, 1997

15 Nishimura, K., "Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis" 146 : 797-808, 2007

16 Davey, S.G., "Meta-analyses of randomised controlled trials" 350 : 1182-, 1997

17 Zamora, J., "Meta-DiSc: a software for metaanalysis of test accuracy data" 6 : 31-, 2006

18 Lijmer, J.G., "Exploring sources of heterogeneity in systematic reviews of diagnostic tests" 21 : 1525-1537, 2002

19 Kim, H.R., "Evaluation of the usefulness of anti-cyclic citrullinated peptide antibodies measured by an automated enzyme immunoassay" 27 : 183-188, 2005

20 Lard, L.R., "Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies" 111 : 446-451, 2001

21 Choi, S.W., "Diagnostic performances of anti-cyclic citrullinated peptides antibody and antifilaggrin antibody in Korean patients with rheumatoid arthritis" 20 : 473-478, 2005

22 Kim, K.H., "Diagnostic performance of the anti-cyclic citrullinated peptide antibodies and rheumatoid factor isotypes in rheumatoid arthritis" 27 : 195-202, 2005

23 Avouac, J., "Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review" 65 : 845-851, 2006

24 Song, J.S., "Comparison of anti-mutated citrullinated vimentin with anti-cyclic citrullinated peptide and rheumatoid factors for the diagnostic value of rheumatoid arthritis. Assessment" 14 : 235-241, 2007

25 Schellekens, G.A., "Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies" 101 : 273-281, 1998

26 van Boekel, M.A., "Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value" 4 : 87-93, 2002

27 Kim, K.H., "Association of anti-cyclic citrullinated peptide antibodies and functional status in rheumatoid arthritis" 13 : 46-51, 2006

28 Saraux, A., "Ability of the American College of Rheumatology 1987 criteria to predict rheumatoid arthritis in patients with early arthritis and classification of these patients two years later" 44 : 2485-2491, 2001

29 Berglin, E., "A combination of autoantibodies to cyclic citrullinated peptide (CCP) and HLA-DRB1 locus antigens is strongly associated with future onset of rheumatoid arthritis" 6 : R303-R308, 2004