自身抗体在类风湿关节炎实验室诊断中的研究进展

类风湿关节炎(rheumatoid arthritis,RA)是一种慢性自身免疫性疾病,该病可引起不可逆转的关节畸形,早期诊断和治疗可延缓疾病的进展。瓜氨酸化、氨甲酰化、氧化及乙酰化是蛋白质翻译后修饰产生的新表位,B细胞针对这些新表位发生免疫应答而产生相应的自身抗体。文章就抗瓜氨酸蛋白抗体(anti citrullin...     

血清抗环瓜氨酸肽抗体与类风湿关节炎合并肺间质纤维化的相关性分析

分析类风湿关节炎(rheumatoid arthritis,RA)患者血清中抗环瓜氨酸肽(CCP)抗体水平与类风湿关节炎患者合并肺间质纤维化的关系.选取RA患者87例,其中合并肺间质纤维化(IPF)22例,单纯RA45例,采用酶联免疫吸附实验(ELISA)检测血清抗CCP抗体滴度,免疫比浊法检测类风湿因子(RF)滴度,...     

7865例抗核抗体检测者中致密斑点型核型结果的回顾性分析

目的 探讨致密斑点型抗核抗体(dense fine speckled,DFS)在抗核抗体(antinuclear antibody,ANA)中的检出率及其在类风湿关节炎(rheumatoid arthritis,RA)患者中的临床价值.方法 回顾性分析2017年至2020年本院就诊患者7 865例ANA检测标本,采用间...     

血清抗肽酰基精氨酸脱亚氨酶4抗体检测在类风湿关节炎诊断中的意义

目的比较类风湿关节炎(rheumatoid arthritis,RA)患者血清中抗肽酰基精氨酸脱亚氨酶4(PADI4)抗体水平和其它风湿病组及正常对照组间的差异,以评估其在RA诊断中的价值。方法采用酶联免疫吸附法(enzyme-linked immunosorbentassay,ELISA)检测患者血清中抗PADI4抗体水平,并研究其与RA患者DAS28评分、抗CCP抗体、抗角蛋白抗体(anti-keratinantibody,AKA)、类风湿因子(rheumatoid factor,RF)等指标的相关性。结果RA患者血清中抗PADI4抗体阳性率为47%,明显高于其它风湿性疾病患者和健康对照组(P<0.05)。抗PADI4抗体对RA诊断的敏感性为43%,特异性为92%。相关性分析显示抗PADI4抗体水平与DAS28评分、抗CCP抗体无相关性(r=-0.025,P=0.82;r=-0.058,P=0.60)。RF阴性患者PADI4抗体阳性50%;AKA阴性的患者PADI4抗体阳性43%;抗CCP抗体阴性的患者抗PADI4抗体阳性60%。结论RA患者血清中抗PADI4抗体有较高的诊断价值,特别有助于RF、抗CCP...     

RF、AKA和抗CCP抗体联检对类风湿关节炎诊断的临床价值

目的:探讨类风湿因子(Rheum atoid factor,RF)、抗角质蛋白抗体(antikeratin antibody,AKA)及抗环瓜氨酸肽(anti-cyc lic c itru llinated peptide,CCP)抗体对类风湿关节炎(rheum atoid arthritis,RA)的临床意义和早期应用价值。方法:对40例类风湿关节炎患者、30例系统性红斑狼疮和30名正常健康体检者进行RF、AKA、抗CCP抗体检测,应用速率散射比浊法测定RF,间接免疫荧光法检测AKA,ELISA法测定抗CCP抗体。结果:40例RA患者血清中,RF灵敏度和特异性分别为70.0%、90.0%,AKA灵敏度和特异性分别为35.0%、96.7%,抗CCP抗体灵敏度和特异性分别为85.0%、93.3%,联检RF、AKA及抗CCP抗体灵敏度和特异性分别为97.07%、99.8%。结论:RF、AKA和抗CCP抗体可作为诊断RA比较特异的血清学指标,三项指标联检可在一定程度上弥补RF对RA的诊断不足,提高RA的阳性诊断率,且有助于疾病的预后判断。     

抗CCP抗体、抗MCV抗体和类风湿因子在早期类风湿关节炎中的诊断价值

目的探讨抗CCP抗体、抗MCV抗体和类风湿因子在早期类风湿关节炎中的诊断价值。方法选择于2016年1月至2017年1月期间在我院就诊的早期类风湿关节炎(RA)患者及其他骨关节病患者各40例,并选择40名同期在我院体检的健康人作为研究对象。其中风湿关节炎患者设为RA组,其他骨关节病患者为疾病对照组,健康人为正常对照组。采用免疫透射比浊法、酶联免疫吸附法(ELISA)、免疫散射比浊法分别测定三组的抗环瓜氨酸肽(CCP)抗体、抗突变型瓜氨酸波形蛋白(MCV)抗体及IgM型类风湿因子(IgM-RF)水平,比较抗CCP抗体、抗MCV抗体、IgM-RF单独检测及三个指标联合检测对早期类风湿性关节炎的诊断价值。结果①RA组的抗CCP抗体、抗MCV抗体、IgM-RF水平均明显高于疾病对照组与正常对照组,差异具有统计学意义(P<0.05);疾病对照组与正常对照组间差异无统计学意义(P>0.05)。②RA组的抗CCP抗体、抗MCV抗体、IgM-RF及联合检测的阳性率均明显高于疾病对照组与正常对照组,差异具有统计学意义(P<0.05);疾病对照组与正常对照组间差异无统计学意义(P>0.05)。③联合检测的灵敏度及阴性预测值均明显高于抗CCP抗体、抗MCV抗体、IgM-RF单独检测,差异具有统计学意义;抗CCP抗体与抗MCV抗体的特异性及阳性预测值均明显高于IgM-RF及联合检测,差异具有统计学意义(P<0.05)。结论早期RA患者的血清中存在抗CCP抗体、抗MCV抗体、IgM-RF的高表达,且其灵敏度及特异性均较高,临床上可联合检测抗CCP抗体、抗MCV抗体及IgM-RF,以提高RA的早期诊断率。     

类风湿关节炎六种指标联合检测的临床意义

目的评价分析抗瓜氨酸化波形蛋白(MCV)抗体、抗葡萄糖-6-磷酸异构酶(GPI)抗体等六项指标在类风湿关节炎(RA)患者血清中的表达与疾病的相关性及应用价值。方法收集110例RA、26例SLE、23例强直性脊柱炎(OA)、20例干燥综合征(SS)患者和50名健康人血清标本,用ELISA检测血清中抗MCV、抗GPI和抗环瓜氨酸肽(CCP)抗体水平,采用间接免疫荧光法检测抗角蛋白(AKA)抗体,采用散射比浊法检测类风湿因子(RF)和hs-CRP水平。结果 4种抗体在RA患者组中的阳性率显著高于非RA疾病组和健康对照组。除AKA抗体阳性率较低(41.8%)外,其余抗体在RA组中的阳性率差异无统计学意义。结论抗MCV和抗GPI抗体诊断RA的敏感度最高;抗CCP抗体的特异性最高,AKA抗体具有较高的特异性,但敏感度最低,联合检测可弥补单项抗体检测造成的漏诊。     

抗CCP抗体和AKA在类风湿关节炎诊断的应用价值

目的 比较抗环瓜氨酸肽抗体(抗CCP抗体)和抗角蛋白抗体(AKA)在类风湿关节炎诊断中作用,探讨RA的早期诊断方法.方法 对已确诊的85例RA患者、74例非RA的自身免疫病患者同时测定抗CCP抗体(ELISA法)、AKA(间接免疫荧光检测).结果 抗CCP抗体对诊断RA的灵敏度和特异性分别为75.3％和93.2％;AKA对RA诊断的灵敏度和特异性分别为89.4％和85.14％.抗CCP抗体的灵敏度与AKA灵敏度差异无统计学意义(P＞0.05),特异性差异有统计学意义(P＜0.05);抗CCP抗体或AKA与二者联合检测的灵敏度差异有统计学意义(P＜0.05),特异性差异有统计学意义(P＜0.05).阳性预测值抗CCP抗体较高,阴性预测值以二者联合检测较好,Youden index二者联合检测比单独检测抗CCP抗体或AKA高.抗CCP抗体和AKA在检测RA组中抗CCP抗体和AKA同时阳性检出58例;抗CCP抗体或AKA阳性共检出85例.抗CCP抗体或AKA阳性率(96.5％)比二者同时阳性率(68.2％)大大提高.结论 抗CCP抗体、AKA对RA具有较好的灵敏度和高度的特异性,联合检测抗CCP抗体和AKA可作为早期RA患者及RF阴性RA患者的早期诊断指标.     

自身抗体和类风湿因子联合检测在类风湿性关节炎中的诊断价值

目的:探讨自身抗体和类风湿因子(Rheumatoid factor,RF)联合检测在类风湿性关节炎(Rheumatoid arthritis,RA)中的诊断价值.方法:选取2019年3月至2020年12月我院收治的RA患者119例,另选同期非RA风湿免疫性疾病患者及健康者各120例,分别纳入RA组、非RA组和对照组.分别采用速率散射比浊法、酶联免疫吸附试验和间接免疫荧光法检测各组RF、抗环瓜氨酸肽(Cyclic citrullinated peptide,CCP)抗体、抗角蛋白抗体(Anti-keratin antibody,AKA)及抗核周因子(Anti-perinuclear factor,APF),并计算阳性率,分析自身抗体与RF联合检测对RA的诊断价值.结果:RA组RF、抗CCP抗体、AKA、APF阳性率均高于非RA组和对照组(P<0.05).单独检测时,RF灵敏度最高,特异度最低(P<0.05);抗CCP抗体、AKA、APF灵敏度、特异度差异均无统计学意义(P>0.05).4项指标联合检测时较单独检测的灵敏度升高,特异度降低.结论:自身抗体和RF对诊断RA均有一定的临床意义,联合检测可提高诊断结果准确性,具有较高的诊断价值.     

抗-CCP抗体和RF在类风湿关节炎诊断中的临床应用

类风湿关节炎(rheumatoid arthritis,RA)是一种常见的自身免疫性疾病.全世界大约有0.5%的人罹患此病[1].目前该病的诊断主要依赖于临床表现,X线检查以及类风湿因子(RF)检查.     

类风湿因子及相关自身抗体对类风湿关节炎的诊断价值

目的探讨类风湿因子（RF）、抗环瓜氨酸肽抗体（抗CCP）及抗角蛋白抗体（AKA）联合检测对类风湿关节炎（RA）的临床诊断价值。方法对80例RA和65例非RA的其他自身免疫病患者检测RF、RF-IgM、抗CCP及AKA 4种指标。结果自身免疫性疾病女性发病较高,以RA组为甚;RA组的RF、RF-IgM、抗CCP及AKA高于其他自身免疫性疾病组;单指标检测RA诊断的敏感性为RF〉RF-IgM〉AKA〉抗CCP,特异性为RF-IgM〉抗CCP〉RF〉AKA。阳性预测值为抗CCP〉RF〉RF-IgM、AKA,阴性预测值为RF〉RF-IgM〉AKA〉抗CCP;以并联或串联方式联合检测均以RF、RF-IgM及抗CCP三联及RF、RF-IgM、抗CCP及AKA四联检测为佳,并联检测的敏感性分别为93%及97%,串联检测的特异性分别为98%及99%。结论 RF、RF-IgM、抗CCP及AKA 4种指标联合检测可提高对RA诊断的敏感性和特异性,对RA的早期诊断有较高价值。     

Comparison and relevance of rheumatoid factors, antikeratin antibodies and anti-cyclic citrullinated peptides antibodies in rheumatoid arthritis

OBJECTIVES: to evaluate specificity and sensibility of the rheumatoid factors (RF), the anti-cyclic citrullinated peptide antibodies (CCP) and the anti-keratin antibodies (AKA) according to the rheumatoid arthritis (RA) diagnosis; pathology other than RA with at least one of these marker positive; the significance of the flocculent fluorescence of the antibodies AKA by indirect immunofluorescence (IIF). METHOD: two hundred forty height patients were studied: 121 RA, 89 inflammatory rheumatisms, 23 non inflammatory rheumatisms, and 15 non rheumatic affections. The RF was investigated by nephelometry, the anti-CCP by immunofluorometry and the AKA by IIF on rat oesophagus. RESULTS: specificity and sensibility were respectively in a retrospective manner: 68% and 83% for the RF, 95% and 76% for the anti- CCP, 83% and 40% for the AKA during RA with evolution of less than one year. The rates of agreements were: RF versus CCP: 81%, RF versus AKA: 57%, CCP versus AKA: 73%. Twelve patients with pathologies different from RA have positive anti-CCP or AKA. Thirty three of the patients with anti-CCP level superior to 130 U/mL have flocculent AKA versus only 5% when the anti-CCP are lower than 130 U/mL. CONCLUSION: the RF and the anti-CCP are complementary in RA. Autoimmune and neoplasic pathologies are sometimes responsible for the positivity of the anti-CCP and the AKA. The flocculent aspect of AKA in IIF may be associated with raised concentrations of anti-CCP.     

抗环瓜氨酸肽抗体检测对类风湿关节炎的临床诊断价值

目的探讨抗环瓜氨酸肽抗体（抗CCP抗体）检测对类风湿关节炎（RA）诊断的意义。方法采用酶联免疫吸附试验（ELISA）检测115份人血清的抗CCP抗体,同时采用免疫透射比浊法定量检测类风湿因子（RF）,包括40例RA患者,45例其它风湿病患者,30名正常人;并分析抗CCP抗体与RF实验结果之间的相关性。结果在40例RA病人中,抗CCP抗体的阳性率为80.0%,在其它风湿病人中的阳性率为7.0%,抗CCP抗体对RA的敏感性和特异性分别为80.0%、96.0%,其敏感性高于RF,但差异无统计学意义（P〉0.05）,特异性明显高于RF（P〈0.05）。联合应用抗CCP抗体与RF进行诊断,二者均阳性时敏感性为65.0%,特异性为97.3%。抗CCP抗体与RF实验结果之间无相关性。结论抗CCP抗体对RA具有较好的敏感性和很高的特异性,可与RF相互补充,联合检测可提高对RA早期诊断的准确性。     

第二代抗环瓜氨酸肽抗体的检测在类风湿关节炎诊断中的意义

目的探讨抗环瓜氮酸肽（CCP）抗体的检测在类风湿关节炎（RA）诊断中的价值。方法ELISA法分别检测108例RA、89例非RA（其它风湿病患者）和78例健康体检者的抗CCP抗体；用间接免疫荧光法和速率散射比浊法检测抗角蛋白抗体（AKA）和类风湿因子（RF），分析CCP抗体的水平及与AKA、RF的相关性。结果抗CCP抗体的阳性率在RA中为87．4％（94／108），在非RA中为8．99％（8／89），正常人为0％（0／78）。3种抗体对RA诊断的敏感性和特异性分别为CCP87．4％、91．01％，AKA58．33％，82．24％，RF81．36％、75．35％。CCP抗体与AKA在RA患者血清中的阳性率之间差异非常显著，与RF差异不显著。3种方法的检测结果间存在相关性。结论用ELISA法检测血清中CCP抗体简便、结果可靠，对RA诊断具有高度的敏感性和特异性。     

Anti-Citrullinated Protein Antibodies in Rheumatoid Arthritis: As Good as it Gets?

Anti-citrullinated protein antibodies (ACPAs) have recently emerged as sensitive and specific serological markers of rheumatoid arthritis (RA), providing superior alternative of the rheumatoid factor (RF) test in the laboratory diagnostics of RA. The first members of this autoantibody family were anti-perinuclear factor (APF) and anti-keratin antibodies (AKA). It became evident that both APF and AKA recognize citrullinated epitopes of filaggrin. Citrullination is a post-translational modification of arginine by deimination, physiologically occurring during apoptosis, inflammation or keratinization. The presence of several citrullinated proteins has been demonstrated in the RA synovium. The identification of citrullinated epitopes as targets for anti-filaggrin antibodies led to the development of the first and later second generation anti-cyclic citrullinated peptide (anti-CCP) antibody assays. The widely used anti-CCP2 assays have high diagnostic sensitivity and specificity, and they also show important predictive and prognostic value in RA. The anti-Sa antibody has been identified a decade ago; however, recent studies confirmed that anti-Sa is directed against citrullinated vimentin, hence it is a new member of the family of ACPAs. The newly developed anti-mutated citrullinated vimentin (anti-MCV) assay has similar diagnostic performance than the anti-CCP2 ELISA; however, the diagnostic spectrum of the anti-MCV test is somewhat different from that of anti-CCP2. It’s especially useful in the diagnosis of RA in RF and anti-CCP2 seronegative patients. The combined application of anti-CCP2 and anti-MCV assays can improve the laboratory diagnostics of RA. The family of ACPAs is expected to expand; there is an increasing need for developing new diagnostic strategies after careful evaluation of the characteristics of the available assays. Zoltán Szekanecz and Lilla Soós with equal contribution.     

Autoantibodies recognizing citrullinated rat filaggrin in an ELISA using citrullinated and non-citrullinated recombinant proteins as antigens are highly diagnostic for rheumatoid arthritis

The objective of the study was to determine the diagnostic value for rheumatoid arthritis (RA) of anti-filaggrin autoantibodies (autoAb) recognizing citrullinated recombinant rat filaggrin (ACRF) in community cases of very early arthritis. To evaluate the diagnostic value of ACRF, were studied sera from patients with different classified rheumatic diseases and healthy subjects (group 1, n= 422) and 314 community cases of very early arthritis (group 2) that were classified as RA (n = 176), non-RA (n = 63) and undifferentiated (n = 75) arthritides after 1 years of follow-up. ACRF were measured using a new ELISA, with results expressed as the difference between the OD value obtained on citrullinated minus that on noncitrullinated rat filaggrin (differential ACRF; dACRF). For both groups, rheumatoid factors (RF), anti-keratin autoAb (AKA) and anti-perinuclear factor (APF) were tested; for group 2, anti-CCP autoAb were also tested. Different reactivity patterns against citrullinated and noncitrullinated filaggrin were observed. Almost all sera reacting with citrullinated but not noncitrullinated filaggrin were from RA patients. Among RA and non-RA sera that recognized both forms of filaggrin, a positive result was obtained only with RA sera. For groups 1 and 2, dACRF sensitivity was 58.4% and 30.7%, and specificity for RA was 99.5% and 98.4%, respectively. In group 2, dACRF specificity for RA was better than that of RF (92.1%), APF (95.2%), AKA (96.8%) and anti-CCP (95.2%). dACRF positive predictive value was high (98.2) and close to that given by the concomitant positivity of RF and anti-CCP autoAb. Despite a high positive correlation between AKA, APF, anti-CCP and dACRF test results, they were complementary since some sera were positive for only one test. Thus, in a community setting, anti-citrullinated rat filaggrin reactivity detected by a new ELISA, whose originality is based on the difference between serum's reactivities on the citrullinated and native forms of filaggrin, had a higher diagnostic value for RA than other autoAb.     

Prevalence of Autoantibodies to Cyclic Citrullinated Peptide in Patients with Rheumatic Diseases other than Rheumatoid Arthritis: A French Multicenter Study

Our objective was to evaluate the prevalence of autoantibodies to cyclic citrullinated peptides (anti-CCP aAbs) in a cohort of patients with a variety of inflammatory or non-inflammatory rheumatic diseases other than rheumatoid arthritis (RA). Six hundred and nine serum samples were tested for anti-CCP aAbs and for rheumatoid factor (RF) using enzyme-linked immunosorbent assays and immunonephelometry. The prevalence of anti-CCP aAbs and RF reached 10% and 25%, respectively, using the positive cutoff value suggested by the manufacturers. Using a higher cutoff value (50 U/ml) for both aAbs, the prevalence was lower with 6% and 16%, respectively. The specificity of both markers for RA thus reached 94% and 84%, respectively. Anti-CCP aAbs were found to be elevated in inflammatory and also in non-inflammatory rheumatic diseases in the same proportion. Clinical data obtained for 36 positive patients showed that 17% developed RA within 5 years. In conclusion, anti-CCP aAbs are clearly more specific than RF for RA. Follow-up of anti-CCP aAbs-positive patients with inflammatory or non-inflammatory rheumatic diseases other than RA could be important considering the predictive value of these aAbs for the development of RA.     

抗CCP抗体与RF联合检测在类风湿关节炎早期诊断中的意义

目的 探究抗CCP抗体与RF联合检测在类风湿关节炎早期诊断中的意义。方法 选取2017年11月~2018年11月我院收治的30例类风湿关节炎患者设为研究组,另选取同期进行健康体检者30例设为对照组,对两组进行抗CCP抗体与RF联合检测,并且分析抗CCP抗体、RF单独及两者联合检测的敏感性、特异性、阳性预测值和阴性预测值。结果 研究组抗CCP抗体阳性率96.67%、RF阳性率93.33%和两者联合检测阳性率86.67%均高于对照组的6.67%、3.33%及3.33%;研究组抗CCP抗体水平（78.65±14.33）U/ml和RF水平（314.22±20.56）IU/ml均高于对照组的（2.69±2.14）U/ml和（10.01±3.54）IU/ml（P＜0.05）。结论 对类风湿关节炎患者抗CCP抗体与RF的诊断敏感度拥有着一定的相似性,但抗CCP抗体特异度高于RF的特异度,若两者联合检测可极大提高敏感度,对于类风湿关节炎患者早期诊断工作的开展拥有着积极的推动作用。     

联检多项指标对类风湿关节炎诊断的临床价值

目的:探讨类风湿因子(Rheum atoid factor,RF)、抗角质蛋白抗体(AKA)、C-反应蛋白(C-reactiveprote in,CRP)和血沉(erythrocyte sed im entation rate,ESR)联检对类风湿关节炎(rheum atoid arthritis,RA)的临床诊断价值。方法:对35例类风湿关节炎患者、30例系统性红斑狼疮和30名正常健康体检者的RF、AKA、CRP及ESR检测,应用速率散射比浊法测定RF和CRP;间接免疫荧光法检测AKA;应用魏氏法测定ESR值。结果:35例RA患者血清中,RF灵敏度和特异性分别为71.4%、91.7%,AKA灵敏度和特异性分别为34.3%、96.7%,CRP灵敏度和特异性分别为91.4%、25%,ESR灵敏度和特异性分别为88.6%、83.3%。联检RF和AKA的灵敏度和特异性分别为81.2%、99.7%,联检RF、AKA、CRP及ESR的灵敏度和特异性分别为99.98%、99.97%。结论:RF、AKA、CRP及ESR可作为RA诊断的血清学指标,且四者联检有助于提高RA诊断的灵敏度及特异性。