抗核抗体检测在自身免疫性疾病中的应用评价

目的 探讨抗核抗体（ANA）检测对自身免疫性疾病诊断的指导意义.方法 回顾性分析2010年1月~2010年12月间在我院就诊的患者血清自身抗体的检测结果,599例患者,其中自身免疫性疾病患者313例,非自身免疫性疾病286例,所有患者血清检测ANA,以Hep-2细胞/肝组织为基质的间接免疫荧光法检测ANA.结果 在自身免疫性疾病中,干燥综合征（SS）、类风湿性关节炎（RA）、混合型结缔组织病（MCTD）和系统性红斑狼疮（SLE）中的阳性率分别为73.43%、53.66%、61.04%和90.63%;在非自身免疫性疾病中的阳性率为21.68%,阳性率明显低于自身免疫性疾病组（P〈0.01）;在自身免疫性疾病组,荧光核型以颗粒型最多见,占47.22%~63.84%.结论 ANA的检测有助于自身免疫性疾病的诊断和筛查.     

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。     

家兔抗角蛋白自身抗体独特型抗体的产生及临床意义

目的 观察长期注射大剂量同种异体抗角蛋白自身抗体（AKautoAb)后,家兔血清中针对抗角蛋白自身抗体（AKautoAb)独特型抗体的产生,方法 肌肉注射亲和层析纯化的AKautoAb(5mg/kg),隔日1次,连续90d,用ELISA检测血清中的抗独特型抗体,结果 注射AKautoAb的家兔产生了针对AKautoAbF(ab′）2片段的抗独特型抗体,于给药4wk血清抗体滴度达高峰,以后逐渐降低,结论 长期注射大剂量同种异体AKautoAb的家兔可产生免疫耐受性。     

抗CCP抗体和抗MCV抗体在RA中的表达及意义

为探讨抗环瓜氨酸肽(cyclic citrullinated peptide, CCP)抗体和抗突变型瓜氨酸波形蛋白(mutated citrullinated vimentin, MCV)抗体在RA中的表达及临床意义,选择185例RA初诊患者作为RA组,70例其他风湿性疾病患者作为疾病对照组,80例健康者作为健康对照组,采用ELISA检测入选对象的血清抗CCP抗体、抗MCV抗体和RF水平,并监测其治疗前后的浓度变化情况。结果显示,抗CCP抗体和抗MCV抗体在RA组患者中的表达水平显著高于疾病对照组和健康对照组(P0.05);抗CCP抗体和抗MCV抗体诊断RA的灵敏度分别为83.8%和91.4%,诊断RF阴性RA的灵敏度分别为65.2%和81.0%。抗CCP抗体和抗MCV抗体在关节肿胀数 3、Sharp评分 50、DAS28高评分RA患者中的水平明显升高(P0.05),抗MCV抗体水平在CRP 50 mg/L、有关节腔积液的RA患者中明显升高(P0.05)。在RA缓解组中,抗MCV抗体水平在治疗3个月后明显下降(P0.05),抗CCP抗体在治疗6个月后明显下降(P0.05);在RA未缓解组中,抗CCP抗体和抗MCV抗体水平在治疗前后差异均无统计学意义(P 0.05)。提示抗CCP抗体和抗MCV抗体不仅在RA诊断和治疗中有较高的临床意义,两者联合检测还有利于对RA患者骨破坏情况、炎症反应等临床特征进行判断。     

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.     

联检抗CCP抗体和RF在RA诊断中的应用

目前,类风湿关节炎（RA）的诊断主要依靠临床症状和体征以及类风湿因子（RF）测定。由于RF对于RA的特异性较差,限制了它在RA中的诊断作用。近年来研究发现,抗环瓜氨酸肽抗体（CCP抗体）对RA的诊断和监测有重要意义。本文探究了抗CCP抗体与RF联检对提高RA诊断的意义。     

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...     

抗CCP抗体和RF联检在RA诊疗中的临床价值

目的：研究抗环瓜氨酸肽（anti-cyclic citrullinated peptide,Anti-CCP）（抗CCP抗体）和RF的检测在类风湿关节炎（RA）诊疗中的临床价值。方法：分别用酶联免疫吸附试验（ELISA）、BeckMan全自动蛋白分析仪同时检测早期RA组（病程〈1年）42例,RA组（病程〉1年）40例,非RA对照组40例患者血清抗CCP抗体和RF。结果：早期RA组、RA组的抗CCP抗体、RF阳性率显著高于非RA对照组（P〈0.05）RA组抗CCP水平显著高于早期RA组（P〈0.01）,两者RF无显著差别（P〉0.05）。RA组与早期RA组CCP抗体与RF二者无相关性。结论：联检抗CCP抗体、RF有助于类风湿的早期诊断和预测病情的进展。     

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。     

检测抗聚丝蛋白抗体在类风湿关节炎诊断中的意义

目的探讨抗聚丝蛋白抗体(AFA)对类风湿关节炎(RA)诊断的价值,并比较与RA的其他早期诊断指标的相关性。方法从人表皮细胞中提取并部分纯化聚丝蛋白(filaggrin)抗原,用于免疫印迹检测(Western blot)103例RA血清标本和140例对照血清,包括系统性红斑狼疮(SLE)、干燥综合征(SS)、骨性关节炎(OA)95份及正常人45份。APF和AKA用间接免疫荧光法检测。结果103例RA病人的AFA阳性率、特异性分别为35.9%,93.7%,显著高于疾病对照组和正常人(P<0.001)。在AFA阳性的37例中,AKA也阳性的为26例,重叠率为70.3%;APF亦阳性的为31例,重叠率为83.8%,AFA与AKA、APF之间存在相关性。结论AFA对RA具有很高的特异性。AFA的检测可用于RA的临床诊断。AFA与APF及AKA有相关性,但不能完全取代它们的检测。     

Subclass distribution of IgG antibodies to the rat oesophagus stratum corneum (so-called anti-keratin antibodies) in rheumatoid arthritis.

Serum IgG, labelling the stratum corneum of the rat oesophagus epithelium, so-called anti-keratin antibodies (AKA) constitute the most specific marker for the diagnosis of rheumatoid arthritis. In this study, we investigated 31 IgG AKA-positive rheumatoid sera and 21 control sera from patients with non-rheumatoid inflammatory rheumatic diseases. The serum level of IgG1,2,3 and 4 was determined by radial immunodiffusion and the subclass distribution of IgG AKA by a three-step semi-quantitative immunofluorescence assay using standard monoclonal antibodies specific for each of the four human IgG subclasses. In the rheumatoid sera, the serum level of IgG1 was found to be significantly increased and the level of IgG2 significantly decreased with regard to the control sera, while the levels of IgG3 and 4 as well as total IgG were in the normal range. IgG1,2,3, and 4 AKA were detected in 27 (87%), 6 (19%), 4 (13%) and 11 (35%) of the 31 rheumatoid sera, respectively, and were found to be independent of the clinical and biological indices of the disease. In spite of inter-individual heterogeneity, two predominant profiles were distinguished: IgG1 (alone) and IgG(1 + 4), which together represented 18 sera (58%). The large predominance of IgG1 AKA and the quasi-absence of IgG2 AKA suggest that the recognized antigen may be partly comprised of protein. Moreover, the high frequency of occurrence of IgG4 AKA might result from chronic exposure to the eliciting antigen, which could be a genuine autoantigen since we demonstrated that it is also present in the stratum corneum of human epidermis.     

Conjugal prevalence of rheumatoid arthritis, rheumatoid factor and other autoantibodies in rheumatoid arthritis

The prevalence of rheumatoid arthritis, rheumatoid factor, antinuclear autoantibodies, thyroglobulin and thyroid `microsomal'' autoantibodies and gastric parietal cell autoantibodies has been studied in 327 husbands and 181 wives of 508 probands with seropositive `definite'' or `classical'' rheumatoid arthritis as defined by the American Rheumatism Association diagnostic criteria. Two husbands and three wives had definite rheumatoid arthritis: this prevalence is no higher than one might expect. A higher prevalence of all five autoantibodies was found in husbands compared with age matched controls, but only in respect of antinuclear autoantibodies and thyroglobulin autoantibody were the differences statistically significant. In the wives only rheumatoid factor showed a significantly higher prevalence as compared with controls. The presence of autoantibodies in husbands and wives showed no relationship to the duration of marital contact nor to the presence of the autoantibodies in the probands. The prevalence of autoantibodies in spouses of probands who developed their arthritis after marriage showed no difference when compared with that in probands who developed their arthritis before marriage.     

Anti-keratin antibodies in rheumatoid arthritis: frequency and correlation with other features of the disease

Anti-keratin antibodies (AKA) were detected in 68 out of 98 patients (69%) with classical or definite rheumatoid arthritis (RA). The intensity of the AKA reaction correlated significantly with articular index (AI), grip strength (GS), erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) concentration, serum amyloid A (SAA) protein concentration, the level of antibodies against single stranded DNA (ssDNA) and the IgM rheumatoid factor (RF) titre. A significantly higher number of patients with nodules and Sj?gren's syndrome were AKA positive compared with patients without extra-articular features (EAFs) and the AKA titre was significantly greater in the former group. The mechanisms underlying appearance of AKA are not known but may relate to an as yet unidentified structural alteration of keratin in this disease or may just reflect the rheumatoid autoimmune diathesis.     

Anti-neutrophil cytoplasm antibodies in rheumatoid arthritis.

Anti-neutrophil cytoplasm antibodies (ANCA) occur occasionally in rheumatoid arthritis (RA), but their incidence and clinical significance have been unclear. In this study we have investigated 58 patients with RA. In 22 patients the disease was inactive and the remaining 36 with active disease were further subdivided into those without clinical evidence of vasculitis (26), those with cutaneous vasculitis (8) and those with systemic vasculitis (2). ANCA were demonstrated by indirect immunofluorescence in 10 of the 58 patients (17%). While both perinuclear (pANCA) and cytoplasmic (cANCA) staining were detected, pANCA were more common (70%). Neutrophil-specific anti-nuclear antibodies (ANNA) were demonstrated in a further eight sera (14%) and ANA were detected on Hep-2 cells in 30 of the 58 sera (52%). ELISAs for the detection of anti-myeloperoxidase and anti-elastase antibodies were then established. Five sera with pANCA and five that contained ANNA were negative for both anti-myeloperoxidase and anti-elastase antibodies, suggesting other as yet unidentified cytoplasmic antigens as the target molecules. However, anti-myeloperoxidase or anti-elastase antibodies were found in four sera that had homogeneous or speckled ANA on both Hep-2 cells and neutrophils. One serum contained both antibodies. The presence of ANCA detected by indirect immunofluorescence or of anti-myeloperoxidase or anti-elastase antibodies in these patients with RA was not associated with disease activity nor with the demonstration of cutaneous vasculitis or renal disease (P NS). A possible association with systemic vasculitis remains to be confirmed. There is an incomplete correlation between indirect immunofluorescence patterns and antibody specificity in ELISA systems.     

Anti-type II collagen antibodies in rheumatoid arthritis

Antibodies to native chick and bovine Type II collagen were measured by radio immunoassay, in 83 rheumatoid arthritis (RA) patients and 14 normal controls. Anti-chick Type II collagen and anti-bovine Type II collagen antibodies were found in 48% and 43% of RA patients, respectively. A strong correlation of antibodies to chick and antibodies to bovine collagen was described, suggesting cross-reactivity between different collagen species. There was an association between the presence of anti-native Type II collagen antibody and the expression of HLA-DR2. It is suggested that the production of anti-collagen antibody may be under genetic control in RA, but not associated with the major genetic marker of disease susceptibility, HLA-DR4.     

Antikeratin antibodies in synovial fluid in rheumatoid arthritis

Serum and synovial fluid of 20 patients with classical or definite rheumatoid arthritis (RA) were tested for antikeratin antibodies (AKA) by indirect immunofluorescence using rat esophagus as antigen. AKA were found in 80% of the RA patients, in serum as well as in synovial fluid. None of the 54 serum control patients were AKA positive in serum. None of the 17 synovial fluid control patients were AKA positive in synovial fluid. F(ab)'2 fragments prepared from AKA positive RA serum retained antibody activity. AKA belonged to the IgG class of immunoglobulins. Corrected for the lower IgG content in synovial fluid, AKA constituted a higher percentage of the IgG in synovial fluid than in serum. This could imply a possibility of local production of AKA in the joint.     

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.