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1 대한내과학회지 : 제 76 권제 2 호 2009 재발성류마티즘의예후인자로서의항 CCP 항체의유용성 대구가톨릭대학교의과대학 1 내과학교실, 2 진단검사의학교실, 3 의학통계학교실 김지영 1 박성훈 1 김성규 1 김상경 2 신임희 3 최정윤 1 Anti-CCP antibodies predict progression of palindromic rheumatism to rheumatoid arthritis Ji-Young Kim, M.D. 1, Sung-Hoon Park, M.D. 1, Seong-Kyu Kim, M.D. 1 Sang-Gyung Kim, M.D. 2, Im-Hee Shin, PhD. 3 and Jung-Yoon Choe, M.D. 1 Departments of 1 Internal Medicine, 2 Laboratory diagnostics and 3 Biostatistics, Catholic University of Daegu School of Medicine, Daegu, Korea Background/Aims: Palindromic rheumatism (PR) is an episodic arthropathy that may precede typical rheumatoid arthritis (RA). The objective of this study was to determine whether anti-cyclic citrullinated peptide (anti-ccp) antibodies in patients with PR contribute to the progression to RA. Methods: The study group included 115 patients who were initially diagnosed with PR. Baseline serum samples were stored and analyzed for the presence of anti-ccp antibodies, APF, and RF or for anti-ccp antibodies and HLA-DR4. A multiple logistic regression analysis was used to identify predictive factors for progression to RA. Results: The anti-ccp antibodies APF and RF were found in 33.3%, 28.9%, and 35.7% of the 115 patients with PR, and 36 (31.3%) of these patients eventually progressed to RA. Comparing the risk factors for patients who progressed to RA (31.3%) and those who did not (68.7%), only the presence of anti-ccp antibodies was found to affect progression to RA (95% CI for OR, ; p). HLA-DR4-positivity was noted in 40% of the patients with PR, although it did not affect progression to RA and was not significantly associated with the presence of anti-ccp antibodies. Conclusions: Anti-CCP antibodies are found more frequently in patients with PR who eventually progress to RA. Therefore, anti-ccp antibody testing of patients with PR may facilitate prediction of progression to RA. (Korean J Med 76: , 2009) Key Words: Palindromic Rheumatism; Anti-CCP antibody 서론재발성류마티즘은일시적인단관절염혹은소수관절염의형태를띄는반복성의염증성관절염이다 1, 2). 재발성류마티즘의중요한임상적의의는질병이경과함에따라류마 티스관절염으로진행할수있다는데있다. 일반적으로재발성류마티즘의장기적인경과는세가지로나뉘어지는데 1) 임상적인관해 2) 영구적인관절침범은없으나반복적으로발생되는일시적관절염 3) 만성적인영구적관절염으로의진행등이그것이다. 대개전체재발성류마티즘환자의 1/3, Received: Accepted: Correspondence to: Jung-Yoon Choe, M.D., Department of Internal Medicine, Catholic University of Daegu School of Medicine, , Daemyung 4-dong, Nam-gu, Daegu , Korea jychoe@cu.ac.kr

2 - The Korean Journal of Medicine: Vol. 76, No. 2, 혹은 1/2의수에서만성적인류마티스관절염으로진행한다고알려져있으며, 진행까지의기간은일정하지가않아서, 수주에서부터 10년까지로다양하게보고되고있다 3). 최근몇몇저자들에의하여재발성류마티즘에서류마티스관절염으로의진행을예측할수있는임상적, 면역학적, 혹은유전학적지표들에대한제한된연구가시행되었다 4-10). 이중에서류마티스인자양성은만성화로진행하는가장중요한지표로인지되었으며, 그밖에높은적혈구침강속도 (ESR), 질병발생시두개이상의관절을동시에침범하는경우, 손가락이나손목관절의침범, 여성, 고령환자등이또다른지표가될수있음을제시하였다 11-15). 그러나류마티스인자가류마티스관절염의진단에있어서특이도가높지못하다는한계가있어, 최근에류마티스관절염진단특이도를매우높이는몇몇종류의항체가개발되었다. 특히최근에는 cyclic citrullinated peptide (CCP) 를사용하여 ELISA법으로항 CCP 항체를검출하는방법이개발되었으며, 류마티스관절염에대하여이항체는 98% 정도의높은특이성이있는것으로보고되고있다 21). 이에저자들은본연구에서항 CCP 항체가재발성류마티즘에서류마티스관절염으로의진행을예측할수있는인자가되는지알아보고자하였다. 대상및방법 1. 연구대상 1998년 1월부터 2005년 12월까지본원류마티스센터에서진료받고있는환자들중첫방문당시재발성류마티즘으로진단받은 115명을대상으로의무기록을중심으로후향적조사를실시하였다. 대상군에포함되는재발성류마티즘은다음의 1)~3) 의기준을모두만족하는경우로정의한다 : 1) 류마티스전문의에의해재발성류마티즘으로진단받은환자 2) 단관절염혹은소수관절염이급성으로발생한후자연적으로소실되는특징이있고, 이런관절증상이반복적으로재발되는경우 3) 그리고다음의기준중에서두가지이상이만족되는경우 : i) 연구자에의하여한번이상관절염발생이관찰된경우, ii) 2년내에 5번이상의관절염발생, iii) 각각다른발작동안 3 부위이상의관절을침범, iv) 정상방사선소견, v) 다른종류의재발성관절염, 즉통풍, 연골석회증, 감염성관절염등을배제할수있는경우. 재발성류마티즘의유병기간은첫관절염발생후가장최근의방문까지의기간으로정의하되, 류마티스관절염으 로진행한경우는류마티스관절염진행까지의기간으로정의하며, 대상군을류마티스관절염으로진행한군과계속재발성류마티즘으로남아있는군으로나누어결과를비교하였다. 2. 연구방법대상군의일반적인특성및진단당시의류마티스인자, antiperinuclear factor (APF, ImmunoThink, Korea), 항CCP항체검사결과를조사하였다. 진단당시시행하지못한검사는 -80 에서보관된대상군의검체를이용하여조사하였다. 류마티스인자는면역혼탁도측정법 (immunoturbidometry) 에의해 Cobas integra RFII (Roche Diagnostics GmbH, Germany) 로검사하였고, APF는면역형광법 (indirect immunofluorescence method) 으로, 항 CCP 항체는 2세대로 DIASTAT TM (Axis-Shield Diagnostics, UK) 을사용하였으며 ELISA 법으로검사하였다. 류마티스인자와항 CCP 항체검사의결과는제조사의권고에따라각각 10 IU/mL, 5 U/mL 이상을양성으로판정하였다. 환자군의진단에있어류마티스인자와항 CCP 항체의민감도와특이도, 진단의정확도를알아보고이환기간에따라조기관절염의진단에있어류마티스인자와항 CCP 항체의민감도와특이도의차이를비교해보았다. 류마티스인자와항 CCP 항체는 115명모두에서조사되었고, APF 검사결과는 83명에서조사되었다. 또한대상군들중무작위로추출된 50명에대해유전자검체를이용한중합체연쇄반응검사로 HLA-DR4 유무를검사하였다. 3. 통계분석결과는 SPSS ver 10.0 통계프로그램을이용하여분석하고, 항 CCP 항체양성군과음성군간의차이는필요에따라카이제곱검정을이용하여비교하였다. 교차비 (odds ratio) 와 95% 신뢰도는회귀분석을이용하였고, 류마티스관절염으로의진행과연관된변수의조사는 Cox 회귀모형을이용하였다. 유의수준은 p 값이 0.05 이하로정의하였다. 결과총환자수는 115명으로남자 48명, 여자 67명이었고, 남녀의비는 1:1.4이었다. 류마티스인자와 APF, 항 CCP 항체의양성율은 35.7% (41명), 28.9% (24명), 33.3% (38명) 이며, 추적관찰기간동안전형적인재발성류마티즘의양상을유지하였던환자는 79명 (68.7%) 이었고, 1987년미국류마티스학회진단기준에합당한류마티스관절염으로진행된환자는

3 - Ji-Young Kim, et al. Prognostic significance of anti-ccp antibody in palindromic rheumatism - Table 1. Baseline characteristics of the patients in the progression of PR to RA groups PR RA (-) PR RA (+) (n=79) (n=36) p-value Age (years, mean±s.e.) 43.7± ± Sex * Male 39 (81.3%) 9 (18.8%) Female 40 (59.7%) 27 (40.3%) RF * Anti-CCP Ab * APF * HLA-DR4 SE 64 (86.5%) 15 (36.6%) 72 (93.5%) 7 (18.4%) 48 (81.4%) 8 (33.3%) 21 (70.0%) 12 (60.0%) 10 (13.5%) 26 (63.4%) 5 (6.5%) 31 (81.6%) 11 (18.6%) 16 (66.7%) 9 (30.0%) 8 (40.0%) Missing cases were excluded; * p-value<0.05; PR, palindromic rheumatism; RA, rheumatoid arthritis; RF, rheumatoid factor; anti-ccp, anti-cyclic citrullinated peptide; APF, antiperinuclear factor; SE, shared epitope 명 (31.3%) 이었다. 재발성류마티즘에서류마티스관절염으로진행된 36명에서그렇지않은 79명과비교시류마티스인자와 APF, 항 CCP 항체의양성율이 63.4% (26명), 66.7% (16명), 81.6% (31 명 ) 으로높은상관관계를나타냈으며 (p), 연령과성별도유의한상관관계를보였으나 (p=0.012, 0.014), HLA-DR4 는상관관계가없는것으로나타났다 (p=0.465)( 표 1). 그리고대상군을항 CCP 항체양성인군 (67%, 38명 ) 과음성인군 (33%, 77명 ) 으로나누어항 CCP 항체와다른인자와의관계를비교한결과성별과류마티스인자, APF 와유의한양의상관관계를보였고 (p=value), 연령과 HLA-DR4는상관관계가없는것으로나타났다 (p=0.072, 1000)( 표 2). 류마티스관절염으로의진행을예측할수있는인자를알아보기위해다변량분석을실시한결과항 CCP 항체만이유의한상관관계를나타내었고 (p-value ), 성별, 나이, 류마티스인자, APF는의미있는결과를보이지않았다 ( 표 3). 고찰재발성류마티즘은일시적인단관절염혹은소수관절염의형태를띄는반복성의염증성관절염으로독립된특이 질환인지, 류마티스관절염의다양한질병형태의한변형인지는논란의여지가있다. 재발성류마티즘은류마티스관절염과는뚜렷이다른임상적특징들이있는데, 류마티스관절염은여성환자에서유병률이훨씬더높은반면재발성류마티즘은남녀발생비가비슷하고, 류마티스관절염은방사선학적골파괴를보이는경우가흔하지만재발성류마티즘은상대적으로매우경한임상경과를보여류마티스관절염으로진행하기전까지는골파괴가거의발생하지않는다. 이러한특징들을바탕으로, 재발성류마티즘이류마티스관절염과는발생원인이다른독립적인질환이라고주장되기도한다 8, 9). 한편, 재발성류마티즘이독립된질환이아니라, 류마티스관절염의다양한임상양상중, 경한형태에불과하며, 병인이동일한한가지질환이라고주장되기도하는데, 이들은류마티스관절염과재발성류마티즘환자에서발견되는자가항체나특정유전인자의종류나발생빈도가비슷하다는것을근거로제시한다 4, 5). 또한재발성류마티즘의치료에관하여는대규모의무작위환자대조군연구가없으며, 대개류마티스의사의경험에의존하는경우가많다. 관절염발생시에만항염증약물을필요에따라복용하기도하고, 관절염이없는시기에도

4 - 대한내과학회지 : 제 76 권제 2 호통권제 582 호 Table 2. Baseline characteristics of the patients in anti-ccp antibody-positive and -negative groups Anti-CCP Ab (-) Anti-CCP Ab (+) (n=77) (n=38) p-value Age (years) 44.2± ± Sex * Male 41 (53.2%) 7 (18.4%) Female 36 (46.8%) 31 (81.6%) RF * 67 (87.0%) 7 (18.4%) 10 (13.0%) 31 (81.6%) APF * 49 (83.1%) 10 (16.9%) 6 (25.0%) 18 (75.0%) HLA-DR4 SE 18 (60.0%) 12 (40.0%) (60.0%) 8 (40.0%) Missing cases were excluded; *p-value<0.05; RF, rheumatoid factor; anti-ccp, anti-cyclic citrullinated peptide; APF, antiperinuclear factor; SE, shared epitope. Table 3. Predictive value of baseline characteristics for the progression of PR to RA by multivariate logistic regression analysis (n=83) Variable b OR (95% CI) p-value Anti-CCP Ab * (=1/=0) Sex (Female=1/Male=0) Age (Years) RF (=1/=0) APF (=1/=0) * p-value<0.05; b, regression coefficient; OR, odds ratio; RF, rheumatoid factor; anti-ccp, anti-cyclic citrullinated peptide; APF, antiperinuclear factor. 지속적으로항류마티스제재를사용하여관절염재발을예방하기위한시도를하기도한다. 이는재발성류마티즘의질병발생원인이명확히밝혀져있지않을뿐아니라, 류마티스관절염으로의진행과같은불량한예후를예측할수있는인자가확실히알려져있지않기때문인것으로생각된다 3). 이상의결과로볼때재발성류마티즘의중요한임상적의의는질병이경과함에따라류마티스관절염으로진행할수있다는데있고, 따라서류마티스관절염으로진행하는재발성류마티즘을미리예측할수있는인자를발견할수있다면재발성류마티즘의적극적인치료에큰도움이될것으로여겨진다. 서론에서언급했듯이몇몇저자들에의하여재발성류마티즘에서류마티스관절염으로의진행을예측할수있는면 역학적, 혹은유전학적지표들에대한제한된연구가시행되었다. 류마티스인자는류마티스관절염의진단에있어서특이도가높지못하다는한계가있어서, 최근에류마티스관절염진단특이도를매우높이는몇종류의항체가개발되었다. 인간구강점막상피세포의핵주위과립에대한 APF와인간표피세포의 filagrin에대한항체인항 keratin 항체가이용될수있고, 류마티스관절염의진단에높은특이도를보이는것으로보고되었으나검사방법상의문제등으로일반적으로이용하기에는어려움이있다. 최근 filaggrin의 arginine기가 peptidylarginine deiminase (PADI) 에의해 citrulline 기로변화가일어나고이런 citrullinated 기를포함한기질에반응하는항체가밝혀지면서, 여기서변형된 cyclic citrullinated peptide에대한항체가류마티스관절염환자의진단에이용

5 - 김지영외 5 인. 재발성류마티즘에서항 CCP 항체의의의 - 되고있다 16-19). 최근까지발표된연구결과들에따르면류마티스관절염의진단에있어항 CCP 항체의민감도는 39 94%, 특이도는 % 까지보고되고있고, 발병 24개월미만의조기류마티스관절염에서도진단적가치가있는것으로발표되었고 20), 미분화관절염으로부터류마티스관절염으로의변화와도유의하게관련되어있으며건강대조군의류마티스관절염의발병의예측하는데도류마티스인자보다높은민감도를나타내는것으로보고되었다 9, 21). 재발성류마티즘에서항 CCP 항체나 APF의양성률에대한연구는매우드물게이루어졌지만, Salvador 등은 63명의재발성류마티즘환자에서항 CCP 항체의양성률이류마티스관절염과비슷하며, 이두가지는면역학적으로동일한질환이라고주장하였다. 이들은향후재발성류마티즘에서항 CCP 항체의임상적인의의즉, 관절염의중증도나류마티스관절염으로의진행과같은예후적중요성에관하여더많은환자들을대상으로충분한기간동안의관찰이필요할것으로제시하였다 4). 그리고최근 Nielen 등은류마티스관절염환자들이임상증상이발현이뚜렷이나타나기수년전부터 IgM 류마티스인자나혹은항 CCP 항체가혈액내에서발견이되므로, 이들항체의검사를통해류마티스관절염발생을예측할수있다고주장하였다 7). 또한 Gaalen 등도류마티스관절염의진단기준을만족하지않는미분류관절염 (undifferentiated arthritis) 환자의경우에항 CCP 항체검사가류마티스관절염발생을예측할수있는인자가된다고보고하였다 6). 이에저자는본연구를통해항 CCP 항체가재발성류마티즘에서류마티스관절염으로의진행을예측할수있는인자가되는지알아보고자했고, 동시에류마티스인자, APF, 연령, 성별의예측인자로써의관련성도알아보았다. 그결과다변량분석을통해항 CCP 항체만이유의한결과를나타내었고, 다른인자들과의관련성은발견되지않았다. 따라서현재까지보고된기존의연구들과본연구결과를바탕으로판단해볼때, 항 CCP 항체가재발성류마티즘의독립적인예후인자로역할을할가능성이높고, 류마티스관절염으로의진행을예측하는매우높은표지자가될것으로판단된다. 이외에도류마티스관절염으로의진행을예측하는유전적인자에대해서도논의되고있다. 류마티스관절염에서 HLA 복합체의역할에대하여는다양한인종에서매우넓게연구가되어왔으며, 류마티스관절염발생에서유전적요인의약 1/3은 HLA 복합체와연관이있는것으로판단이되고있다. HLA-DR class II allele이관절염발생항원을 T 임파구 로전달하는역할을할것이라고하는일명 shared epitope (SE) 가설이일반적으로받아들여지고있는데, 이SE 대립유전자는류마티스관절염발생위험을증가시킬뿐아니라더증증의임상경과를나타낸다는것이밝혀져있다. 재발성류마티즘에서 SE의연구는최근 147명의재발성류마티즘환자에서조사된한연구가있다. 이보고에의하면 HLA-DRB1*0401과 *0404의빈도가정상대조군에비하여높지만, 류마티스관절염환자와는비슷하였다 8). 류마티스관절염의중증도를결정하고예후를반영하는인자들이특정항체나 SE단독만으로는설명할수없다는한계에대한인식이널리있던중항 CCP 항체와 SE을동시에연구한흥미로운보고가있었다. 이연구에서는 HLA- DRB1 SE 대립유전자의발현은항 CCP 항체양성과유의한연관성이있었으며, 또한 SE양성, 항 CCP 항체양성환자들이, SE 음성, 항 CCP 항체양성인환자나 SE 양성, 항 CCP 항체음성인환자혹은 SE와항 CCP 항체둘다음성인환자들보다방사선학적관절파괴가더뚜렷한것이확인되었다. 이를통하여, HLA class II 감수성대립유전자가항 CCP 항체생산과밀접한연관이있다는것과 SE 대립유전자와항 CCP 항체를동시에가지는환자에서더심한임상양상을나타내는것이밝혀졌다 5). 이에근거해본연구에서도 115명중무작위로추출한 50 명을대상으로 SE의예후예측인자로써의관련성을보았으나의미있는연관성을발견할수없었다. 이에대해서는차후에좀더대규모의연구가필요할것으로생각된다. 본연구의제한점으로단일센터에서모집된환자를대상군으로했으므로선택편견 (selection bias) 의가능성이있다. 또한의무기록을중심으로한후향적조사이므로침범관절의개수, 침범부위, 증상의빈도등예후에영향이미칠것이라여겨지는임상적지표들의기록이미비하여통계분석에포함되지않은제한점이있다. 또한 APF와 HLA-DR4 검사도보관된검체의부족으로 83명, 50명으로전체대상군보다적게조사되었다. 만약이를보정하면실제로는항 CCP 항체의예측인자관련성이본연구의결과보다조금낮아지거나, 재발성류마티즘에서류마티스관절염으로의진행예측에다른인자들과의관련성이나타날수도있을것으로생각된다. 요약항 CCP 항체가재발성류마티즘에서류마티스관절염으로의진행을예측할수있는인자가될수있고, 기존에주

6 - The Korean Journal of Medicine: Vol. 76, No. 2, 장된것처럼재발성류마티즘이류마티스관절염과동일한면역학적기초를가지는지를추측할수있을것으로기대되며, 향후재발성류마티즘의치료에있어서, 불량한예후인자를가진환자를선별적으로적극적인약물치료를시행하는새로운치료기준이정립될수도있을것으로생각된다. 중심단어 : 재발성류마티즘 ; 항 CCP 항체 REFERENCES 1) Hench P, Rosenberg E. A new oft-recurring disease of joints (arthritis, periarthritis, para-arthritis) apparently producing no articular residues: report of thirty-four cases. Arch Intern Med 73: , ) Daniel L. Intermittent and periodic arthritis syndrome. In: Koopman WJ, ed. Arthritis and allied conditions. 14 ed. p , Philadelphia, Lippincott Williams and Wilkins, ) Sanmarti R, Canete JD, Salvador G. Palindromic rheumatism and other relapsing arthritis. Best Pract Res Clin Rheumatol 18: , ) Salvador G, Gomez A, Vinas O, Ercilla G, Canete JD, Munoz- Gomez J, Sanmarti R. Prevalence and clinical significance of anti-cyclic citrullinated peptide and antikeratin antibodies in palindromic rheumatism: an abortive form of rheumatoid arthritis? Rheumatology 42: , ) van Gaalen FA, van Aken J, Huizinga TW, Schreuder GM, Breedveld FC, Zanelli E, van Venrooij WJ, Verweij CL, Toes RE, de Vries RR. Association between HLA class II genes and autoantibodies to cyclic citrullinated peptides (CCPs) influences the severity of rheumatoid arthritis. Arthritis Rheum 50: , ) van Gaalen FA, Linn-Rasker SP, van Venrooij WJ, de Jong BA, Breedveld FC, Verweij CL, Toes RE, Huizinga TW. Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study. Arthritis Rheum 50: , ) Nielen MM, van Schaardenburg D, Reesink HW, van de Stadt RJ, van der Horst-Bruinsma IE, de Koning MH, Habibuw MR, Vandenbroucke JP, Dijkmans BA. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum 50: , ) Maksymowych WP, Suarez-Almazor ME, Buenviaje H, Cooper BL, Degeus C, Thompson M, Russell AS. HLA and cytokine gene polymorphisms in relation to occurrence of palindromic rheumatism and its progression to rheumatoid arthritis. J Rheumatol 29: , ) Rantapaa-Dahlqvist S, de Jong BA, Berglin E, Hallmans G, Wadell G, Stenlund H, Sundin U, van Venrooij WJ. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum 48: , ) Reitblat T, Litinsky I, Caspi D, Elkayam O. Antiphospholipid syndrome and palindromic rheumatism: a new possible association. Rheumatol Int 25: , ) Guerne PA, Weisman MH. Palindromic rheumatism: part of or apart from the spectrum of rheumatoid arthritis. Am J Med 93: , ) Gonzalez-Lopez L, Gamez-Nava JI, Jhangri GS, Ramos-Remus C, Russell AS, Suarez-Almazor ME. Prognostic factors for the development of rheumatoid arthritis and other connective tissue diseases in patients with palindromic rheumatism. J Rheumatol 26: , ) Wajed MA, Brown DL, Currey HL. Palindromic rheumatism: clinical and serum complement study. Ann Rheum Dis 36:56-61, ) Byun JW. Clinical presentation of palindromic rheumatism. J Korean Rheum Assoc 10: , ) Hannonen P, Mottonen T, Oka M. Palindromic rheumatism: a clinical survey of sixty patients. Scand J Rheumatol 16: , ) Nienhuis RL, Mandema E. A new serum factor in patients with rheumatoid arthritis: the antiperinuclear factor. Ann Rheum Dis 23: , ) Young BJ, Mallya RK, Leslie RD, Clark CJ, Hamblin TJ. Antikeratin antibodies in rheumatoid arthritis. Br Med J 2:97-99, ) Vincent C, de Keyser F, Masson-Bessiere C, Sebbag M, Veys EM, Serre G. Anti-perinuclear factor compared with the so called antikeratin antibodies and antibodies to human epidermis filaggrin, in the diagnosis of arthritides. Ann Rheum Dis 58:42-48, ) Schellekens GA, de Jong BA, van den Hoogen FH, van de Putte LB, van Venrooij WJ. Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest 101: , ) Park SH, Kim JY, Kim SK, Choe JY, Kim SK, Shin IH. Diagnostic significance of anti-ccp antibody in Korean early rheumatoid arthritis. J Korean Rheum Assoc 14: , ) Avouac J, Gossec L, Dougados M. Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review. Ann Rheum Dis 65: ,

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( ) 06.jkra043.hwp 대한류마티스학회지 Vol. 14, No. 3, September, 2007 원저 한국인조기류마티스관절염에서항 CCP 항체의진단적의의 대구가톨릭대학교의과대학내과학교실, 진단검사의학교실 *, 의학통계학교실 ** 박성훈ㆍ김지영ㆍ김성규ㆍ최정윤ㆍ김상경 * ㆍ신임희 ** =Abstract= Diagnostic Significance of Anti-CCP Antibody