抗环瓜氨酸肽抗体在类风湿关节炎诊断中的意义及对关节侵蚀的预测价值
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摘要
目的：本实验旨在研究一种新的血清抗体(抗环瓜氨酸肽抗体，抗CCP抗体)在RA诊断中的意义，以及它与RA关节侵蚀发生的关系，并结合其它的RA相关指标，对RA关节侵蚀的多个危险因子进行综合评价。
方法：利用ELISA法检测抗CCP抗体，间接免疫荧光法(ⅡF)检测抗角蛋白抗体(AKA)，速率散射比浊法(Rate Nephelometry)检测类风湿因子(RF)，评价三者诊断RA的价值。以Larsen关节评分法将RA患者分为无(轻微)关节侵蚀组(group1)和严重关节侵蚀组(group2)，分析抗CCP抗体、AKA、RF在两组中的分布。对抗CCP抗体、AKA、RF、ANA(ⅡF法测得)、血沉(ESR)、C-反应蛋白(CRP)、类风湿结节进行单因素分析，考察它们与RA关节侵蚀的关系。将上述因子逐一引入Logistic回归方程中，建立针对RA关节侵蚀的危险预测系统，研究各个因子在该系统中的权重。
结果：1)三种抗体诊断RA的敏感性和特异性分别为：抗CCP抗体(49％，94％)、AKA(50％，93％)、RF(79％，67％)；三种抗体两两组合后诊断RA的敏感性和特异性分别为：抗CCP抗体+AKA(21％，99％)，抗CCP抗体+RF(35％，97％)，AKA+RF(33％，97％)。2)三种抗体在group2中的阳性率明显高于group1(P＜0.05)。3)在三种抗体中，抗CCP抗体针对RA关节侵蚀的阳性预测值(PPV)
最高(0.68)，其t匕值比(OR)为6.71。4)Logistie回归分析表明，抗CCp抗体、
AKA、CRP、类风湿结节与RA的关节侵蚀有关，其中C即所占权重最大(OR
12.07)。
结论:l)抗CCP抗体是RA良好的诊断指标，可以广泛应用于临床。2)
抗CCP抗体与AKA、即联合使用可以进一步提高诊断的准确性。3)抗CCP
抗体与RA关节侵蚀密切相关，是RA关节侵蚀的危险因素之一。4)对RA关节
侵蚀的多种危险因素进行综合考察有助于临床医师判断RA的预后。
OBJECTIVE We explored the diagnostic significance of anti-cyclic citrullinated peptide(CCP) antibody(anti-CCP) and the role it plays in the articular erosion in patients with rheumatoid arthritis(RA). Furthermore, We evaluate several risk factors comprehensively combining with other laboratory and clinical markers.
METHOD We evaluated the diagnostic significance of anti-CCP, AKA and RF using ELISA, IIF and rate nephelometry respectively.75 RA patients were devided into 2 groups(none or limited radiographic damege group(group 1) and severe radiographic damage group (group 2) ) based on Larsen's score system. We investigated the distribution of anti-CCP, AKA and RF in patients of the two groups. A univariate analysis was used to determine whether anti-CCP, AKA, RF, ANA, ESR, CRP or cutaneous nodules plays a role on articular erosion in RA. To determine which had the best predictive value for severe radiographic damage, all variables were entered into a logistic regression model. RESULT 1) The sensitivity and specificity of Anti-CCP, AKA and RF were
49%,94% ; 50%,93% ; 79%,67% respectively. When assayed together, these parameters would be changed if both markers were positive(anti-CCP and AKA, anti-CCP and RF, AKA and RF). 2) The positive rate of these three markers were much higher in group 2 than that in group 1. 3) Among these three markers, anti-CCP had the highest positive predictive value(0.68) and OR(6.71) for articular erosion in RA. 4) Logistic regression analysis showed a strong correlation between anti-CCP , AKA, CRP or cutaneous nodules and less favourable disease outcomes. Anti-CCP had the strongest correlation with severe radiographic damage.
CONCLUSION 1) Anti-CCP is a satisfactory marker for RA and can be used in clinical practice extensively. 2) Diagnostic accuracy would be raised when anti-CCP combined with AKA and RF. 3) Anti-CCP has a strong correlation with severe radiographic damage. 4) To investigate multiple risk factors of articular erosion will be helpful to pridict the outcome of RA.
方法：利用ELISA法检测抗CCP抗体，间接免疫荧光法(ⅡF)检测抗角蛋白抗体(AKA)，速率散射比浊法(Rate Nephelometry)检测类风湿因子(RF)，评价三者诊断RA的价值。以Larsen关节评分法将RA患者分为无(轻微)关节侵蚀组(group1)和严重关节侵蚀组(group2)，分析抗CCP抗体、AKA、RF在两组中的分布。对抗CCP抗体、AKA、RF、ANA(ⅡF法测得)、血沉(ESR)、C-反应蛋白(CRP)、类风湿结节进行单因素分析，考察它们与RA关节侵蚀的关系。将上述因子逐一引入Logistic回归方程中，建立针对RA关节侵蚀的危险预测系统，研究各个因子在该系统中的权重。
结果：1)三种抗体诊断RA的敏感性和特异性分别为：抗CCP抗体(49％，94％)、AKA(50％，93％)、RF(79％，67％)；三种抗体两两组合后诊断RA的敏感性和特异性分别为：抗CCP抗体+AKA(21％，99％)，抗CCP抗体+RF(35％，97％)，AKA+RF(33％，97％)。2)三种抗体在group2中的阳性率明显高于group1(P＜0.05)。3)在三种抗体中，抗CCP抗体针对RA关节侵蚀的阳性预测值(PPV)
最高(0.68)，其t匕值比(OR)为6.71。4)Logistie回归分析表明，抗CCp抗体、
AKA、CRP、类风湿结节与RA的关节侵蚀有关，其中C即所占权重最大(OR
12.07)。
结论:l)抗CCP抗体是RA良好的诊断指标，可以广泛应用于临床。2)
抗CCP抗体与AKA、即联合使用可以进一步提高诊断的准确性。3)抗CCP
抗体与RA关节侵蚀密切相关，是RA关节侵蚀的危险因素之一。4)对RA关节
侵蚀的多种危险因素进行综合考察有助于临床医师判断RA的预后。
OBJECTIVE We explored the diagnostic significance of anti-cyclic citrullinated peptide(CCP) antibody(anti-CCP) and the role it plays in the articular erosion in patients with rheumatoid arthritis(RA). Furthermore, We evaluate several risk factors comprehensively combining with other laboratory and clinical markers.
METHOD We evaluated the diagnostic significance of anti-CCP, AKA and RF using ELISA, IIF and rate nephelometry respectively.75 RA patients were devided into 2 groups(none or limited radiographic damege group(group 1) and severe radiographic damage group (group 2) ) based on Larsen's score system. We investigated the distribution of anti-CCP, AKA and RF in patients of the two groups. A univariate analysis was used to determine whether anti-CCP, AKA, RF, ANA, ESR, CRP or cutaneous nodules plays a role on articular erosion in RA. To determine which had the best predictive value for severe radiographic damage, all variables were entered into a logistic regression model. RESULT 1) The sensitivity and specificity of Anti-CCP, AKA and RF were
49%,94% ; 50%,93% ; 79%,67% respectively. When assayed together, these parameters would be changed if both markers were positive(anti-CCP and AKA, anti-CCP and RF, AKA and RF). 2) The positive rate of these three markers were much higher in group 2 than that in group 1. 3) Among these three markers, anti-CCP had the highest positive predictive value(0.68) and OR(6.71) for articular erosion in RA. 4) Logistic regression analysis showed a strong correlation between anti-CCP , AKA, CRP or cutaneous nodules and less favourable disease outcomes. Anti-CCP had the strongest correlation with severe radiographic damage.
CONCLUSION 1) Anti-CCP is a satisfactory marker for RA and can be used in clinical practice extensively. 2) Diagnostic accuracy would be raised when anti-CCP combined with AKA and RF. 3) Anti-CCP has a strong correlation with severe radiographic damage. 4) To investigate multiple risk factors of articular erosion will be helpful to pridict the outcome of RA.
引文
1 Paimela L, Gripengerg M, Kurki P, et al. Antikeratin antibodies: diagnostic and prognostic markers for early rheumatoid arthritis. Ann Rheum Dis, 1992, 51:743-6.
2 李鸿斌，李小峰，甘晓丹等．抗核周因子等四种抗体联合检测在早期类风湿关节炎诊断中的意义．中华医学杂志，2000，80：20-4．
3 Despres N, Boire G, Lopez-Longo F J, et al. The Sa system: a novel antigen-antibody system specific for rheumatoid arthritis. J Rheumatol, 1994, 21:1027-33.
4 Vincent C, Simon M, Sebbag M, et al. Immunoblotting detection of autoantibodies to human epidermis filaggrin: a new diagnostic test for rheumatoid arthritis. J Rheumatol, 1998, 25:838-46.
5 Menard HA, Lapointe E, Rochdi M, et al. Insights into rheumatoid arthritis derived from a Sa immune system. Arthritis Res, 2000, 2:429-32.
6 Schellekens GA, Visser H, de Jong BAW, et al. The diagnostic properties of rheumatoid arthritis recognizing a cyclic citrullinated peptide. Arthritis Rheum, 2000, 43:155-63.
7 曾小峰，艾脉兴，甘晓丹等．抗环瓜氨酸肽抗体检测在类风湿关节炎中的意义．中华风湿病学杂志，2001，5：281-4．
8 Boini S, Guillemin F. Radiographic scoring methods as outcome measures in rheumatoid arthritis: properties and advantages. Ann Rheum Dis, 2001, 60:817-27.
9 Gerard A, Schellekens GA, Hendrik Visser, et al. The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum, 2000, 43:155-63.
10 Vincent C, Simon M, Sebbag M, et al. Immunoblotting detection of
auto-antibodies to human epidermis filaggrin: a new diagnostic test for rheumatoid arthritis. J Rheumatol, 1998, 25: 838-46.
11 Anil Vasishta. Diagnosing early-onset rheumatoid arthritis: The role of anti-CCP antibodies. American Clinical Laboratory, 2002, 8:34-6.
12 Nicola Bizzaro, Giovanni Mazzanti, Elio Tonutti, et al. Diagnostic accuracy of the anti-citrulline antibody assay for rheumatoid arthritis. Clinical Chemistry, 2001, 47:1089-93.
13 Furst DE. Predictors of worsening clinical variables and outcomes in rheumatoid arthritis. Rheum Dis Clin North Am, 1994,20:309-19.
14 Paimelar L, Gripenberg M, Kurki P, et al. Antikeratin antibodies: Diagnostic and prognostic markers for early rheumatoid arthritis. Ann Rheum Dis, 1992, 51:743-6.
15 Van Zenben D, Hazes JMW, Zwinderman AH, et al. Factors predicting outcome of rheumatoid arthritis: results of a followup study. J Rheumatol, 1993, 20:1288-96.
16 Combe B, Eliaou JF, Daures JP, et,al. Prognostic factors in rheumatoid arthritis. Comparative study of two subsets of patients according to severity of articular damage. Br J Rheumatol, 1995, 34:529-34.
2 李鸿斌，李小峰，甘晓丹等．抗核周因子等四种抗体联合检测在早期类风湿关节炎诊断中的意义．中华医学杂志，2000，80：20-4．
3 Despres N, Boire G, Lopez-Longo F J, et al. The Sa system: a novel antigen-antibody system specific for rheumatoid arthritis. J Rheumatol, 1994, 21:1027-33.
4 Vincent C, Simon M, Sebbag M, et al. Immunoblotting detection of autoantibodies to human epidermis filaggrin: a new diagnostic test for rheumatoid arthritis. J Rheumatol, 1998, 25:838-46.
5 Menard HA, Lapointe E, Rochdi M, et al. Insights into rheumatoid arthritis derived from a Sa immune system. Arthritis Res, 2000, 2:429-32.
6 Schellekens GA, Visser H, de Jong BAW, et al. The diagnostic properties of rheumatoid arthritis recognizing a cyclic citrullinated peptide. Arthritis Rheum, 2000, 43:155-63.
7 曾小峰，艾脉兴，甘晓丹等．抗环瓜氨酸肽抗体检测在类风湿关节炎中的意义．中华风湿病学杂志，2001，5：281-4．
8 Boini S, Guillemin F. Radiographic scoring methods as outcome measures in rheumatoid arthritis: properties and advantages. Ann Rheum Dis, 2001, 60:817-27.
9 Gerard A, Schellekens GA, Hendrik Visser, et al. The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum, 2000, 43:155-63.
10 Vincent C, Simon M, Sebbag M, et al. Immunoblotting detection of
auto-antibodies to human epidermis filaggrin: a new diagnostic test for rheumatoid arthritis. J Rheumatol, 1998, 25: 838-46.
11 Anil Vasishta. Diagnosing early-onset rheumatoid arthritis: The role of anti-CCP antibodies. American Clinical Laboratory, 2002, 8:34-6.
12 Nicola Bizzaro, Giovanni Mazzanti, Elio Tonutti, et al. Diagnostic accuracy of the anti-citrulline antibody assay for rheumatoid arthritis. Clinical Chemistry, 2001, 47:1089-93.
13 Furst DE. Predictors of worsening clinical variables and outcomes in rheumatoid arthritis. Rheum Dis Clin North Am, 1994,20:309-19.
14 Paimelar L, Gripenberg M, Kurki P, et al. Antikeratin antibodies: Diagnostic and prognostic markers for early rheumatoid arthritis. Ann Rheum Dis, 1992, 51:743-6.
15 Van Zenben D, Hazes JMW, Zwinderman AH, et al. Factors predicting outcome of rheumatoid arthritis: results of a followup study. J Rheumatol, 1993, 20:1288-96.
16 Combe B, Eliaou JF, Daures JP, et,al. Prognostic factors in rheumatoid arthritis. Comparative study of two subsets of patients according to severity of articular damage. Br J Rheumatol, 1995, 34:529-34.