类风湿关节炎生物学指标:血清与关节液来源抗体的效能分析
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摘要
背景:目前常规类风湿因子检测对类风湿性关节炎诊断的敏感性和特异性均不高,抗环瓜氨酸肽抗体(anti-cyclic citrullinated peptide antibody,抗CCP抗体)和抗突变型瓜氨酸波形蛋白抗体(anti-modified citrullinated vimentin antibody,抗MCV抗体)日渐被使用,但其血清浓度与关节液浓度的关系仍不清楚。目的:探讨抗CCP抗体、抗MCV抗体对类风湿关节炎早期诊断的临床应用价值。方法:采用ELISA法定量检测16例早期类风湿关节炎患者和6例其他疾病(排除类风湿关节炎诊断)患者血清和关节液中抗CCP抗体、抗MCV抗体浓度,同时收集患者血清类风湿因子等临床资料。分别计算血清和关节液中抗CCP抗体、抗MCV抗体的敏感性和特异性,并分析二者之间的相关性。结果与结论:①抗CCP抗体对早期类风湿关节炎诊断具有良好的敏感性和特异性,可作为类风湿关节炎早期诊断的血清学指标。血清和关节液抗CCP抗体有相同的诊断效用;②抗MCV抗体对早期类风湿关节炎诊断有良好的敏感性和特异性,与抗CCP抗体具有类似的诊断价值;③血清类风湿因子对早期类风湿关节炎的敏感性和特异性均较抗CCP抗体及抗MCV抗体降低;④抗CCP抗体与抗MCV抗体联合检测可提高诊断结果,二者之间存在正相关。
BACKGROUND: The sensitivity and specificity of common rheumatoid factor are not high in the diagnosis of rheumatoid arthritis. Anti-cyclic citrullinated peptide antibody and anti-modified citrullinated vimentin antibody are gradually used, but their serum contents associated with synovial fluid concentration remain unclear. OBJECTIVE: To evaluate the application value of anti-cyclic citrullinated peptide antibody and anti-modified citrullinated vimentin antibody in the early diagnosis of rheumatoid arthritis. METHODS: Anti-cyclic citrullinated peptide antibody and anti-modified citrullinated vimentin antibody levels in serum and synovial fluid in 16 patients with early rheumatoid arthritis and 6 cases of other diseases(excluding rheumatoid arthritis) were detected by ELISA, and other clinical data were collected. The sensitivity and specificity of serum anti-cyclic citrullinated peptide antibody in serum and synovial fluid were calculated, respectively to explore its correlation. RESULTS AND CONCLUSION:(1) The sensitivity and specificity of serum anti-cyclic citrullinated peptide antibody were good in the diagnosis of early rheumatoid arthritis, which could be used as a serum indicator. The sensitivity and specificity of synovial fluid anti-cyclic citrullinated peptide antibody was the same with the serum anti-cyclic citrullinated peptide antibody.(2) The sensitivity and specificity of serum anti-modified citrullinated vimentin antibody were good in the diagnosis of early rheumatoid arthritis, which had the similar value with anti-cyclic citrullinated peptide antibody.(3) The sensitivity and specificity of serum rheumatoid factor in diagnosis of early rheumatoid arthritis were lower than those of anti-cyclic citrullinated peptide antibody and anti-modified citrullinated vimentin antibody.(4) In summary, the combined detection of anti-cyclic citrullinated peptide antibody and anti-modified citrullinated vimentin antibody can improve the diagnosis results. There is positive correlation between anti-cyclic citrullinated peptide antibody and anti-modified citrullinated vimentin antibody.
BACKGROUND: The sensitivity and specificity of common rheumatoid factor are not high in the diagnosis of rheumatoid arthritis. Anti-cyclic citrullinated peptide antibody and anti-modified citrullinated vimentin antibody are gradually used, but their serum contents associated with synovial fluid concentration remain unclear. OBJECTIVE: To evaluate the application value of anti-cyclic citrullinated peptide antibody and anti-modified citrullinated vimentin antibody in the early diagnosis of rheumatoid arthritis. METHODS: Anti-cyclic citrullinated peptide antibody and anti-modified citrullinated vimentin antibody levels in serum and synovial fluid in 16 patients with early rheumatoid arthritis and 6 cases of other diseases(excluding rheumatoid arthritis) were detected by ELISA, and other clinical data were collected. The sensitivity and specificity of serum anti-cyclic citrullinated peptide antibody in serum and synovial fluid were calculated, respectively to explore its correlation. RESULTS AND CONCLUSION:(1) The sensitivity and specificity of serum anti-cyclic citrullinated peptide antibody were good in the diagnosis of early rheumatoid arthritis, which could be used as a serum indicator. The sensitivity and specificity of synovial fluid anti-cyclic citrullinated peptide antibody was the same with the serum anti-cyclic citrullinated peptide antibody.(2) The sensitivity and specificity of serum anti-modified citrullinated vimentin antibody were good in the diagnosis of early rheumatoid arthritis, which had the similar value with anti-cyclic citrullinated peptide antibody.(3) The sensitivity and specificity of serum rheumatoid factor in diagnosis of early rheumatoid arthritis were lower than those of anti-cyclic citrullinated peptide antibody and anti-modified citrullinated vimentin antibody.(4) In summary, the combined detection of anti-cyclic citrullinated peptide antibody and anti-modified citrullinated vimentin antibody can improve the diagnosis results. There is positive correlation between anti-cyclic citrullinated peptide antibody and anti-modified citrullinated vimentin antibody.
引文
[1]Ford JA, Solomon DH. Challenges in Implementing Treat-to-Target Strategies in Rheumatology. Rheum Dis Clin North Am. 2019;45(1):101-112.
[2]Zhang X, Mu R, Wang X, et al. The impact of rheumatoid arthritis on work capacity in Chinese patients:a cross-sectional study. Rheumatology(Oxford). 2015;54(8):1478-1487.
[3]McArdle A, Pennington S, FitzGerald O. Clinical Features of Psoriatic Arthritis:a Comprehensive Review of Unmet Clinical Needs. Clin Rev Allergy Immunol. 2018;55(3):271-294.
[4]Angelotti F, Parma A, Cafaro G, et al. One year in review 2017:pathogenesis of rheumatoid arthritis. Clin Exp Rheumatol.2017;35(3):368-378.
[5]Cozzi F, Ciprian L, Carrara M, et al. Balneotherapy in chronic inflammatory rheumatic diseases-a narrative review. Int J Biometeorol. 2018;62(12):2065-2071.
[6]De Moel EC, Derksen VFAM, Trouw LA, et al. In RA,becoming seronegative over the first year of treatment does not translate to better chances of drug-free remission. Ann Rheum Dis. 2018;77(12):1836-1838.
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[8]Alamanos Y, Drosos AA. Epidemiology of adult rheumatoid arthritis. Autoimmun Rev. 2005;4(3):130-136.
[9]Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis.Lancet. 2016;388(10055):2023-2038.
[10]Schellekens GA, Visser H, de Jong BA, et al. The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum. 2000;43(1):155-163.
[11]Kastbom A, Roos Ljungberg K, Ziegelasch M, et al. Changes in anti-citrullinated protein antibody isotype levels in relation to disease activity and response to treatment in early rheumatoid arthritis. Clin Exp Immunol. 2018;194(3):391-399.
[12]Mathsson Alm L, Fountain DL, Cadwell KK, et al. The performance of anti-cyclic citrullinated peptide assays in diagnosing rheumatoid arthritis:a systematic review and meta-analysis. Clin Exp Rheumatol. 2018;36(1):144-152.
[13]Bang H, Egerer K, Gauliard A, et al. Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis. Arthritis Rheum. 2007;56(8):2503-2511.
[14]Díaz-Toscano ML, Olivas-Flores EM, Zavaleta-Mu?iz SA, et al. Comparison of two assays to determine anti-citrullinated peptide antibodies in rheumatoid arthritis in relation to other chronic inflammatory rheumatic diseases:assaying anti-modified citrullinated vimentin antibodies adds value to second-generation anti-citrullinated cyclic peptides testing.Biomed Res Int. 2014;2014:198198.
[15]Nass FR, Skare TL, Goeldner I, et al. Analysis of four serum biomarkers in rheumatoid arthritis:association with extra articular manifestations in patients and arthralgia in relatives.Rev Bras Reumatol Engl Ed. 2017;57(4):286-293.
[16]Meyer PWA, Ally MTM, Hodkinson B, et al. Comparison of the diagnostic potential of three anti-citrullinated protein antibodies as adjuncts to rheumatoid factor and CCP in a cohort of South African rheumatoid arthritis patients.Rheumatol Int. 2018;38(6):993-1001.
[17]Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria:an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569-2581.
[18]Sun P, Wang W, Chen L, et al. Diagnostic value of autoantibodies combined detection for rheumatoid arthritis. J Clin Lab Anal. 2017;31(5):e22086.
[19]Luime JJ, Colin EM, Hazes JM, et al. Does anti-mutated citrullinated vimentin have additional value as a serological marker in the diagnostic and prognostic investigation of patients with rheumatoid arthritis? A systematic review. Ann Rheum Dis. 2010;69(2):337-344.
[20]Hitchon CA, El-Gabalawy HS. Immune features of seronegative and seropositive arthritis in early synovitis studies. Curr Opin Rheumatol. 2002;14(4):348-353.
[21]Gavril?BI, Ciofu C, Stoica V. Biomarkers in Rheumatoid Arthritis, what is new. J Med Life. 2016;9(2):144-148.
[22]Maksymowych WP, Naides SJ, Bykerk V, et al. Serum14-3-3η is a novel marker that complements current serological measurements to enhance detection of patients with rheumatoid arthritis. J Rheumatol. 2014;41(11):2104-2113.
[23]Shi J, van Steenbergen HW, van Nies JA, et al. The specificity of anti-carbamylated protein antibodies for rheumatoid arthritis in a setting of early arthritis. Arthritis Res Ther. 2015;17:339.
[24]Al-Shukaili A, Al-Ghafri S, Al-Marhoobi S, et al. Evaluation of anti-mutated citrullinated vimentin antibodies, anti-cyclic citrullinated peptide antibodies and rheumatoid factor in omani patients with rheumatoid arthritis. Int J Rheumatol.2012;2012:285854.
[25]Li L, Wen W, Jia R, et al. GITRL is associated with increased autoantibody production in patients with rheumatoid arthritis.Clin Rheumatol. 2016;35(9):2195-2202.
[26]Quismorio FP Jr, Kaufman RL, Beardmore T, et al. Reactivity of serum antibodies to the keratin layer of rat esophagus in patients with rheumatoid arthritis. Arthritis Rheum. 2008;58(2Suppl):S69-74.
[27]Hernández-Molina G, Nu?ez-Alvarez C, Avila-Casado C, et al.Usefulness of IgA Anti-α-fodrin Antibodies in Combination with Rheumatoid Factor and/or Antinuclear Antibodies as Substitute Immunological Criterion in Sj?gren Syndrome with Negative Anti-SSA/SSB Antibodies. J Rheumatol. 2016;43(10):1852-1857.
[28]Roodenrijs NMT, de Hair MJH, van der Goes MC, et al.Characteristics of difficult-to-treat rheumatoid arthritis:results of an international survey. Ann Rheum Dis. 2018;77(12):1705-1709.
[29]Alessandri C, Agmon-Levin N, Conti F, et al. Anti-mutated citrullinated vimentin antibodies in antiphospholipid syndrome:diagnostic value and relationship with clinical features.Immunol Res. 2017;65(2):524-531.
[30]Musaelyan A, Lapin S, Nazarov V, et al. Vimentin as antigenic target in autoimmunity:A comprehensive review. Autoimmun Rev. 2018;17(9):926-934.
[2]Zhang X, Mu R, Wang X, et al. The impact of rheumatoid arthritis on work capacity in Chinese patients:a cross-sectional study. Rheumatology(Oxford). 2015;54(8):1478-1487.
[3]McArdle A, Pennington S, FitzGerald O. Clinical Features of Psoriatic Arthritis:a Comprehensive Review of Unmet Clinical Needs. Clin Rev Allergy Immunol. 2018;55(3):271-294.
[4]Angelotti F, Parma A, Cafaro G, et al. One year in review 2017:pathogenesis of rheumatoid arthritis. Clin Exp Rheumatol.2017;35(3):368-378.
[5]Cozzi F, Ciprian L, Carrara M, et al. Balneotherapy in chronic inflammatory rheumatic diseases-a narrative review. Int J Biometeorol. 2018;62(12):2065-2071.
[6]De Moel EC, Derksen VFAM, Trouw LA, et al. In RA,becoming seronegative over the first year of treatment does not translate to better chances of drug-free remission. Ann Rheum Dis. 2018;77(12):1836-1838.
[7]Bas S, Perneger TV, Seitz M, et al. Diagnostic tests for rheumatoid arthritis:comparison of anti-cyclic citrullinated peptide antibodies, anti-keratin antibodies and IgM rheumatoid factors. Rheumatology(Oxford). 2002;41(7):809-814.
[8]Alamanos Y, Drosos AA. Epidemiology of adult rheumatoid arthritis. Autoimmun Rev. 2005;4(3):130-136.
[9]Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis.Lancet. 2016;388(10055):2023-2038.
[10]Schellekens GA, Visser H, de Jong BA, et al. The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum. 2000;43(1):155-163.
[11]Kastbom A, Roos Ljungberg K, Ziegelasch M, et al. Changes in anti-citrullinated protein antibody isotype levels in relation to disease activity and response to treatment in early rheumatoid arthritis. Clin Exp Immunol. 2018;194(3):391-399.
[12]Mathsson Alm L, Fountain DL, Cadwell KK, et al. The performance of anti-cyclic citrullinated peptide assays in diagnosing rheumatoid arthritis:a systematic review and meta-analysis. Clin Exp Rheumatol. 2018;36(1):144-152.
[13]Bang H, Egerer K, Gauliard A, et al. Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis. Arthritis Rheum. 2007;56(8):2503-2511.
[14]Díaz-Toscano ML, Olivas-Flores EM, Zavaleta-Mu?iz SA, et al. Comparison of two assays to determine anti-citrullinated peptide antibodies in rheumatoid arthritis in relation to other chronic inflammatory rheumatic diseases:assaying anti-modified citrullinated vimentin antibodies adds value to second-generation anti-citrullinated cyclic peptides testing.Biomed Res Int. 2014;2014:198198.
[15]Nass FR, Skare TL, Goeldner I, et al. Analysis of four serum biomarkers in rheumatoid arthritis:association with extra articular manifestations in patients and arthralgia in relatives.Rev Bras Reumatol Engl Ed. 2017;57(4):286-293.
[16]Meyer PWA, Ally MTM, Hodkinson B, et al. Comparison of the diagnostic potential of three anti-citrullinated protein antibodies as adjuncts to rheumatoid factor and CCP in a cohort of South African rheumatoid arthritis patients.Rheumatol Int. 2018;38(6):993-1001.
[17]Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria:an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569-2581.
[18]Sun P, Wang W, Chen L, et al. Diagnostic value of autoantibodies combined detection for rheumatoid arthritis. J Clin Lab Anal. 2017;31(5):e22086.
[19]Luime JJ, Colin EM, Hazes JM, et al. Does anti-mutated citrullinated vimentin have additional value as a serological marker in the diagnostic and prognostic investigation of patients with rheumatoid arthritis? A systematic review. Ann Rheum Dis. 2010;69(2):337-344.
[20]Hitchon CA, El-Gabalawy HS. Immune features of seronegative and seropositive arthritis in early synovitis studies. Curr Opin Rheumatol. 2002;14(4):348-353.
[21]Gavril?BI, Ciofu C, Stoica V. Biomarkers in Rheumatoid Arthritis, what is new. J Med Life. 2016;9(2):144-148.
[22]Maksymowych WP, Naides SJ, Bykerk V, et al. Serum14-3-3η is a novel marker that complements current serological measurements to enhance detection of patients with rheumatoid arthritis. J Rheumatol. 2014;41(11):2104-2113.
[23]Shi J, van Steenbergen HW, van Nies JA, et al. The specificity of anti-carbamylated protein antibodies for rheumatoid arthritis in a setting of early arthritis. Arthritis Res Ther. 2015;17:339.
[24]Al-Shukaili A, Al-Ghafri S, Al-Marhoobi S, et al. Evaluation of anti-mutated citrullinated vimentin antibodies, anti-cyclic citrullinated peptide antibodies and rheumatoid factor in omani patients with rheumatoid arthritis. Int J Rheumatol.2012;2012:285854.
[25]Li L, Wen W, Jia R, et al. GITRL is associated with increased autoantibody production in patients with rheumatoid arthritis.Clin Rheumatol. 2016;35(9):2195-2202.
[26]Quismorio FP Jr, Kaufman RL, Beardmore T, et al. Reactivity of serum antibodies to the keratin layer of rat esophagus in patients with rheumatoid arthritis. Arthritis Rheum. 2008;58(2Suppl):S69-74.
[27]Hernández-Molina G, Nu?ez-Alvarez C, Avila-Casado C, et al.Usefulness of IgA Anti-α-fodrin Antibodies in Combination with Rheumatoid Factor and/or Antinuclear Antibodies as Substitute Immunological Criterion in Sj?gren Syndrome with Negative Anti-SSA/SSB Antibodies. J Rheumatol. 2016;43(10):1852-1857.
[28]Roodenrijs NMT, de Hair MJH, van der Goes MC, et al.Characteristics of difficult-to-treat rheumatoid arthritis:results of an international survey. Ann Rheum Dis. 2018;77(12):1705-1709.
[29]Alessandri C, Agmon-Levin N, Conti F, et al. Anti-mutated citrullinated vimentin antibodies in antiphospholipid syndrome:diagnostic value and relationship with clinical features.Immunol Res. 2017;65(2):524-531.
[30]Musaelyan A, Lapin S, Nazarov V, et al. Vimentin as antigenic target in autoimmunity:A comprehensive review. Autoimmun Rev. 2018;17(9):926-934.