Shared epitope classification methods according to Gregersen and de Vries allow adequate characterization of patients with rheumatoid arthritis in a Colombian population

Introduction: The most important genetic association in rheumatoid arthritis (RA) is presented with some alleles from the HLA-DRB1 gene that encode the shared epitope (SE). Objectives: To apply the SE classification methods of Gregersen, de Vries, Raychaudhuri, Mattey, and Tezenas du Montcel in a group of Colombian patients with RA and determine the most common HLA-DRB1 alleles in the population. Methods: RA diagnosis, genetic study of the HLA-DRB1 region using Luminex technology in 50 RA and 50 healthy subjects. For the classification analysis, Fisher's exact test and chi-squared test were applied. Tables were created to count the RA-related alleles. We used odds ratio to determine the risk between the presence of the shared epitope (SE) and anti-cyclic citrullinated peptides (Anti-CCP). Results: Gregersen and de Vries methods were suitable for the characterization of RA in this population (p = .006). The most prevalent HLA-DRB1 alleles in the RA group were 14:02,04:04, 08:02,04:05, and 10:01. High frequencies of the 07:01, 03:01,13:02,01:02, and 12:01 HLA-DRB1 alleles were found in the healthy population. HLA-DRB1 alleles with similar distribution in both populations were 04:07, 15:01, 11:01, 16:02, and 01:01. A high frequency of SE + was observed in Anti-CCP + individuals (63.15%); however, this was not statistically significant [OR2.4 (.63-9.01); p = .19]. Conclusion: The SE classification methods of Gregersen and de Vries were adequate in characterizing RA in a Colombian population group. An equivalence of 100% was verified between the susceptibility alleles defined by de Vries and the alleles assigned as SE according to Gregersen.

Introducción: La asociación genética más importante en artritis reumatoide (AR) se presenta con algunos alelos del gen HLA DRB1 que codifican el epítope compartido (EC). Objetivos: Aplicar los métodos de clasificación de EC de Gregersen et al., de Vries et al., Raychaudhuri et al., Mattey et al., y Tezenas du Montcel et al., en un grupo de pacientes colombianos con AR, y determinar los alelos HLA DRB1 más frecuentes en esta población. Métodos: Diagnóstico para AR, estudio genético de la región HLA DRB1 por tecnología Luminex® de 50 sujetos AR y 50 sanos. Para análisis comparativos de clasificaciones EC, se aplicaron las pruebas test exacto de Fisher y Chi-cuadrado y se realizaron tablas de conteos para los alelos relacionados con AR. Se estimó la razón de odds para determinar el riesgo entre la presencia de EC y los anticuerpos antipéptidos cíclicos citrulinados (anti-PCC). Resultados: Los métodos de Gregersen et al. y de Vries et al. fueron adecuados para la caracterización de AR en esta población (p = 0,006). Los alelos HLA DRB1 más prevalentes en el grupo AR fueron 14:02, 04:04, 08:02, 04:05 y 10:01. Se encontraron altas frecuencias de los alelos HLA DRB1 07:01, 03:01,13:02, 01:02 y 12:01 en población sana. Alelos HLA DRB1 con distribución similar en ambas poblaciones fueron: 04:07, 15:01, 11:01, 16:02 y 01:01. Se observó alta frecuencia de individuos EC+ en el grupo AR anti-PCC+ (63,15%); no obstante, sin asociación estadística (OR: 2,4 [0,63-9,01]; p = 0,19). Conclusión: Los métodos de clasificación para EC de Gregersen et al. y de Vries et al. fueron adecuados caracterizando AR en un grupo de población colombiana. Se corroboró equivalencia del 100% entre los alelos de susceptibilidad definidos por de Vries y los alelos asignados como EC según Gregersen et al.

Independence of carbohydrate-deficient isoforms of transferrin and cyclic citrullinated peptides in rheumatoid arthritis / Independência de isoformas de transferrina deficiente em carboidrato e peptídeos citrulinados cíclicos na artrite reumatoide

ABSTRACT Objective: The aim of this study was to assess the relationship between the two types of posttranslational modifications of proteins in RA: glycosylation on the example of carbohydrate-deficient transferrin and citrullination by means of autoantibodies to cyclic citrullinated peptides. Methods: The study was carried out in 50 RA patients. CDT was measured using N Latex CDT immunonephelometric test, the results were presented in absolute and relative units. Anti-CCP were measured using the chemiluminescent method and rheumatoid factor by immunoturbidimetric method. Results: 80% of RA patients were positive for anti-CCP, 70% for RF and 62% for both, anti-CCP and RF. The level of %CDT was significantly elevated, but absolute CDT level was not changed. The mean absolute CDT concentration was higher in anti-CCP positive patients than that in anti-CCP negative. CDT (absolute and relative concentration) did not correlate with anti-CCP and RF. However, serum RF significantly correlated with anti-CCP. %CDT did not correlate with anti-CCP, but absolute level correlated with anti-CCP only in anti-CCP negative and RF negative patients. CDT did not correlate with RF, but solely with anti-CCP in anti-CCP negative patients. Anti-CCP correlated with DAS 28 only in anti-CCP negative RA, but CDT (absolute and relative units) correlated with DAS 28 in all patients and in anti-CCP positive RA. Conclusions: These results suggest that the changes in CDT and anti-CCP concentrations are not associated with oneself and indicate on the independence of these posttranslational modifications in rheumatoid arthritis. Only the alterations in transferrin glycosylation reflected the activity of RA.

RESUMO Objetivo: Avaliar a relação entre os dois tipos de modificações pós-translacionais de proteínas na AR: glicosilação no caso da transferrina deficiente em carboidrato (TDC) e citrulinação por meio dos anticorpos no caso do antipeptídeo citrulinado cíclico (anti-CCP). Métodos: O estudo foi feito em 50 pacientes com AR. A TDC foi medida com o teste imunonefelométrico N Latex CDT e os resultados foram apresentados em unidades absolutas e relativas. O anti-CCP foi mensurado com o método quimioluminescente e o fator reumatoide (FR) pelo método imunoturbidimétrico. Resultados: Dos pacientes com AR, 80% foram positivos para anti-CCP, 70% para FR e 62% para ambos (anti-CCP e FR). A percentagem de transferrina total (%TDC) esteve significativamente elevada, mas o nível absoluto de TDC não esteve alterado. A concentração média de TDC absoluta foi maior nos pacientes anti-CCP positivos do que naqueles anti-CCP negativos. A TDC (concentração absoluta e relativa) não se correlacionou com o anti-CCP e o FR. No entanto, o FR sérico se correlacionou significativamente com o anti-CCP. O percentual de TDC não se correlacionou com o anti-CCP, mas seu nível absoluto se correlacionou com o anti-CCP apenas em pacientes FR negativos e anti-CCP negativos. A TDC não se correlacionou com o FR, somente com o anti-CCP em pacientes anti-CCP negativos. O anti-CCP se correlacionou com o DAS 28 apenas nos pacientes com AR anti-CCP negativos, mas a TDC (unidades absolutas e relativas) se correlacionou com o DAS 28 quando considerados todos os pacientes com AR e em pacientes com AR anti-CCP positivos. Conclusões: Esses resultados sugerem que as alterações na TDC e as concentrações de anti-CCP não estão associadas e indicam a independência dessas modificações pós-translacionais na artrite reumatoide. Apenas as alterações na glicosilação da transferrina refletem a atividade da AR.

Frecuencia de anticuerpos antipéptido cíclicocitrulinado y factor reumatoide en pacientescon enfermedades reumatológicas de un centrode reumatología, Medellín, Colombia / Frequency of anti-cyclic citrullinated peptide antibodies and rheumatoid factor in patients with rheumatic diseases from a rheumatology outpatient center in Medellin, Colombia

Introducción: El inicio oportuno de la terapia en artritis reumatoide evita el dano˜ articular,y para ello es necesario un diagnóstico precoz. La detección del factor reumatoide y de losanticuerpos antipéptido cíclico citrulinado forma parte del abordaje diagnóstico inicial delpaciente con artritis.Objetivo: Determinar la frecuencia de factor reumatoide y de anticuerpos antipéptido cíclicocitrulinado en pacientes con artritis reumatoide y otras enfermedades reumatológicas, atendidosen un centro ambulatorio de reumatología, en Medellín, Colombia.Métodos: Evaluamos la presencia de factor reumatoide y de anticuerpos antipéptido cíclicocitrulinado en 246 sujetos (64 con artritis reumatoide, 80 con otras enfermedades reumatológicas,61 con osteoartritis y 41 sanos o con fibromialgia).Resultados: En los pacientes con artritis reumatoide la frecuencia de factor reumatoide yde anticuerpos antipéptido cíclico citrulinado y doble positividad fue: 86, 83 y 80%, respectivamente;y en otras enfermedades reumatológicas: 12,5%; 6% y 1%. Ningún sujeto confibromialgia o sano resultó positivo para antipéptido cíclico citrulinado, pero hasta un 5%presentó positividad para factor reumatoide...

IntroductionThe initiation of therapy in rheumatoid arthritis prevents joint damage, but this requires an early diagnosis. The detection of rheumatoid factor and anti-cyclic citrullinated peptide is part of the initial diagnostic approach of patients with arthritis.ObjectiveTo determine the frequency of rheumatoid factor and anti-cyclic citrullinated peptide in patients with rheumatoid arthritis and other rheumatic diseases in patients of a rheumatology outpatient center in Medellin, Colombia.MethodsAn evaluation is made of the presence of rheumatoid factor and anti-cyclic citrullinated peptide in 246 subjects (64 with rheumatoid arthritis, 80 with other rheumatic diseases, 61 with osteoarthritis and 41 healthy or with fibromyalgia).ResultsIn rheumatoid arthritis patients the frequency of rheumatoid factor, anti-cyclic citrullinated peptide, and double positivity (rheumatoid factor and anti-cyclic citrullinated peptide simultaneously) was: 86%, 83% and 80%, respectively, and in other rheumatologic diseases it was: 12.5%, 6%, and 1%, respectively. No subjects with fibromyalgia, or healthy, tested positive for anti-cyclic citrullinated peptide, but up to 5% showed positivity for rheumatoid factor.ConclusionThe possibility of positivity for rheumatoid factor and anti-cyclic citrullinated peptides in diseases other than rheumatoid arthritis and in healthy people should be taken into account, and particularly rheumatoid factor...

Decoy receptor3 in rheumatoid arthritis patient and its clinical relevance / 中华风湿病学杂志

Objective To test serum decoy receptor 3 (DcR3) concentration in patients with rheumatoid arthritis (RA),and analyze its clinical significance.Methods The serum from 180 RA patients,29 osteoarthritis (OA) patients,60 systemic lupus erythematosus (SLE) patients,30 Sj(o)gren's syndrome (SS) patients and 100 healthy donators were selected.The serum DcR3 concentrations of the two groups were detected by enzyme-linked immunosorbent assay (ELISA).The correlation between serum DcR3 levels and clinical features of patients with RA were investigated.T test,x2 test and Spearman's correlation analysis were used for statistical analysis with software SPSS 16.0.Results Serum DcR3 levels in RA patients [(202±261)ng/ml] were significantly higher than those of the healthy controls [(32±31) ng/ml,t=5.33,P＜0.01],OA patients [(90±33)ng/ml,t=1.998,P＜0.01],SLE patients [(41±56)ng/ml,t=3.19,P＜0.01],and SS patients [(25±31) ng/ml,t=2.50,P＜0.01].The DcR3 cut value was 45.86 ng/ml for the diagnoses of RA,the sensitivity and specificity was 0.991 and 0.765 respectively.The levels of serum DcR3 in RA patients were related with rheumatoid factor (RF) IgM,RF-IgG,anti-cyclic citrullinated peptide antibodies (anti-CCP) and C3.Conclusion Serum DcR3 level is significantly elevated in RA and it is significantly associated with immunological index of RA including RF-IgM,RF-IgG,C3 and anti-CCP antibody,which may be a factor for unfavorable prognosis of RA patients.

Detection of anti-cyclic citrullinated peptide antibodies in patients with rheumatoid arthritis: The clinical significance / 第二军医大学学报

Rheumatoid arthritis (RA) is an autoimmune disease involving multiple joints, and currently it still leads to high disability rate of the joints and high mortality. Early diagnosis and treatment can effectively reduce joint deformities. The recently discovered anti-citrullinated peptide antibodies(ACPA) can be detected before damage to the joints occurs. Compared with classical rheumatoid factor (RF) ACPA has higher specificity and similar sensitivity in diagnosing RA. Some studies have showned that anti-cyclic citrullinated peptide antibodies play an important role in the early diagnosis of RA and prediction of prognosis; epidemiological evidences also show that ACPA plays an important role on the pathogenesis of RA.

Detection of anti-cyclic citrullinated peptide antibodies in patients with rheumatoid arthritis: Theclinical significance / 第二军医大学学报

Rheumatoid arthritis (RA) is an autoimmune disease involving multiple joints, and currently it still leads to high disability rate of the joints and high mortality. Early diagnosis and treatment can effectively reduce joint deformities. The recently discovered anti-citrullinated peptide antibodies(ACPA) can be detected before damage to the joints occurs. Compared with classical rheumatoid factor (RF) ACPA has higher specificity and similar sensitivity in diagnosing RA. Some studies have showned that anti-cyclic citrullinated peptide antibodies play an important role in the early diagnosis of RA and prediction of prognosis; epidemiological evidences also show that ACPA plays an important role on the pathogenesis of RA.

The specificity of anti-cyclic citrullinated peptide antibodies in the diagnosis of rheumatoid arthritis from a large cohort study in the Chinese / 中华内科杂志

Objective To determine the sensitivity and specificity of anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies) in the diagnosis of rheumatoid arthritis. Method A total of 1018healthy donors, 212 patients with rheumatoid arthritis, 435 patients with other connective tissue disease were recruited to this study. Anti-CCP antibodies and IgM-rheumatoid factor (RF) were determined by ELISA according to manufacturer instructions, with a cut-off of 20U. Result The frequency of positive anti-CCP antibodies in patients with rheumatoid arthritis is 48.1% (n = 102 ), higher than healthy donors (2.6%,n = 26) and patients with other connective tissue diseases (3.7%, n = 16). The specificity of anti-CCP antibodies is 97.4%. The titer of anti-CCP antibodies in patients with rheumatoid arthritis (429. 7 U) is much higher than that in healthy donors (29. 3 U ) and patients with other connective tissue diseases (36. 5 U). The frequency of positive IgM-RF in patients with rheumatoid arthritis is 94. 3% whilst only21.5% in healthy donors. The false positivity rate of IgM-RF is higher than anti-CCP antibody. Conclusion Anti-CCP antibodies is a highly specific autoantibody in the diagnosis of rheumatoid arthritis.

Anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis.

Objective. Prevalence and clinical significance of anti-cyclic citrullinated peptide (CCP) antibodies in Indian patients with juvenile idiopathic arthritis (JIA). Methods. Anti-CCP antibodies were determined by enzyme-linked immunosorbent assay (ELISA) in 78 patients with JIA which included all 3 major subtypes of the disease: pauciarticular, polyarticular afld systemic onset. Values above 5 relative units were taken as positive. Associations between antiCCP antibodies and clinical and laboratory and radiological parameters were determined. Results. Anti-CCP antibodies were positive in only 2 of 34 (5.9%) patients with pauciarticular JIA and 3 of 17 (17.6%) of systemic,.pnset JIA, whereas it was positive in 13 of 27 (48.1%) of polyarticular JIA patients (p < 0.001). Furthermore, it was seen that among patients with polyarticular JIA, RF-lgM positive patients had higher rate of anti-CCP antibody positivity with 7 of 8 (87.5%) patients having positive anti-CCP antibody (p<0.001). Similarly, patients with erosions (11/19; p<0.001) and deformities (5/-10; p<0.001) were found to have significant association with anti-CCP antibody positivity. Conclusion. Anti-CCP antibodies could be detected more frequently in the sera of JIA patients with severe manifestations like- erosions and deformity. It was also more significantly associated with seropositive polyarticular JIA than other types. It can be presumed from these results that anti-CCP antibodies can be used as a marker to predict severe course of JIA at the onset to guide optimal aggressive therapy.

Detection of anti-cyclic citrullinated peptide antibodies by time-resolved fluoroimmunoassay / 中华风湿病学杂志

Objective To develop a method for detecting anti-cyclic citrullinated peptide (anti-CCP)in the serum of rheumatoid arthritis patients. Methods The range of lineage correlation, precision and detection range of time-resolved fluoroimmunoassay (TRFIA) was analyzed. Thirty-two positive serum of antiCCP, and the sera from 50 health blood donors, 32 SLE patients, 26 patients with SS, 10 patients with scleroderma, 20 patients with MCTD and 18 patients with MS were tested in this study. The clinical specificity was assessed. The consistency between TRFIA and ELISA was analyzed by Mc Nemar test. Results Analyzed by SPSS 13.0 statistical software, the intra-batch precision (n=20) rate was 2%, 3% and 4% respectively, and the inter-batch precision (n=8) was 3%, 4% and 7% respectively for 3 different concentrations. The clinical specificity was 98%, 97%, 96%, 100%, 95% and 100% in the sera of healthy blood donors, SL,E, SS,scleroderma, MCTD and MS patients respectively. The correlation coefficient was 0.989.The average recovery rate was 101%, and the sensitivity was 1 U/ml. When compared with ELISA, the detection range of TRFIA was wider and also with betterstability. Conclusion TRFIA is a stable method with high sensitivity and wide detection range. It can be used to detect anti-CCP antibody. It is important for early diagnosis of RA and monitor the curative effect of RA. And this method has potential to be used in clinical diagnosis.

Evaluation of ACR 1987 criteria and the role of anti-cyclic citrullinated peptide antibodies for the diagnosis of rheumatoid arthritis / 中华风湿病学杂志

Objective To revise the American College of Rheumatology classification criteria for rheumatoid arthritis(RA)with anti-cyclic citrullinated peptide(anti-CCP)antibodies and to evaluate its utility in the diagnosis of Chinese patients.Methods All patients from the Department of Rheumatology and Immunology of Peking University People's Hospital who had arthritis complaints in recent two years were enrolled.Patients were divided into RA group and non-RA group according to the clinical diagnosis by experienced rheumatologists.The diagnostic value of ACR criteria and the anti-CCP revised criteria(RA-6,RA-7 and RA-8)were evaluated by analyzing the clinical and laboratory parameters.Results A total of 604 patients were included in the study.312 patients were diagnosed as RA and 292 were diagnosed as other rheumatic diseases by rheumatologists.For those patients who had disease course for less than 2 years,the sensitivity of 1987 ACR criteria,RA-6,RA-7 and RA-8 criteria was 82.0%,91.0%.87.0%and 87.0%,respectively.The specificity of them was 95.6%,83.9%,95.6%and 95.6%.respectively.The sensitivity of 1987 ACR criteria,RA-6,RA-7 and RA-8 criteria for all the RA patients was 92.3%,96.8%.94.6%and 94.6%,respectively.The speciflcity of them was 92.8%,83.6%,92.8%and 92.8%.respectively.Conclusion The 1987 ACR criteria have high sensitivity and specificity in established RA.but its sensitivity in early RA is low.The RA-6criteria can improve the sensitivity dramatically but with reduced specificity.The RA-7 criteria can increase the sensitivity without sacrifice the specificity,especially in early RA patients.It may be used as a new set of classification criteria in clinical practice.

Anti-cyclic citrullinated peptide antibodies and rheumatoid factor in leprosy patients with articular involvement

The objective of the present research was to evaluate the usefulness of anti-cyclic citrullinated peptide (anti-CCP) antibodies and the IgM rheumatoid factor (IgM RF) test for the differential diagnosis of leprosy with articular involvement and rheumatoid arthritis (RA). Anti-CCP antibodies and IgM RF were measured in the sera of 158 leprosy patients (76 with and 82 without articular involvement), 69 RA patients and 89 healthy controls. Leprosy diagnosis was performed according to Ridley and Jopling classification criteria and clinical and demographic characteristics of leprosy patients were collected by a standard questionnaire. Leprosy patients with any concomitant rheumatic disease were excluded. Serum samples were obtained from all participants and frozen at _20°C. Measurement of anti-CCP antibodies and IgM RF were performed by ELISA, using a commercial second-generation kit, and the latex agglutination test, respectively. Anti-CCP antibodies and IgM RF were detected in low frequencies (2.6 and 1.3 percent, respectively) in leprosy patients and were not associated with articular involvement. Among healthy individuals both anti-CCP antibodies and IgM RF were each detected in 3.4 percent of the subjects. In contrast, in the RA group, anti-CCP antibodies were present in 81.2 percent and IgM RF in 62.3 percent. In the present study, both anti-CCP antibodies and IgM RF showed good positive predictive value for RA, helping to discriminate between RA and leprosy patients with articular involvement. However, anti-CCP antibodies were more specific for RA diagnosis in the population under study.

Association of Anti-cyclic Citrullinated Peptide (CCP) Antibodies and Functional Status in Rheumatoid Arthritis / 대한류마티스학회지

No abstract available.

Diagnostic Performance of the Anti-Cyclic Citrullinated Peptide Antibodies and Rheumatoid Factor Isotypes in Rheumatoid Arthritis / 임상검사와정도관리

BACKGROUND: The rheumatoid factor (RF) is the only serological marker in American College of Rheumatology criteria for the diagnosis of rheumatoid arthritis (RA), but its specificity is not satisfactory for the diagnosis of RA. We evaluated the diagnostic performance of a new anti-cyclic citrullinated peptide antibodies (anti-CCP) test with those of RF isotypes for the diagnosis of RA. METHODS: Anti-CCP was determined in 186 serum samples: 110 from RA patients, 30 from non-RA patients(rheumatic diseases other than RA), and 46 normal individuals. IgM RF by latex fixation test and IgA RF by ELISA were also assayed in each samples, and the results were compared to anti-CCP for sensitivity and specificity by the receiver-operating characteristic curve on optimal cut-off values. RESULTS: The sensitivity of anti-CCP was highest (80.0%) and the sensitivities of IgM RF, IgA RF were 71.8%, 45.5%, respectively. The sensitivity increased (from 80.0% to 88.2%) especially in the combination of anti-CCP with IgM RF. The specificity of IgA RF by ELISA were highest (96.0 %) and the specificity of anti-CCP (94.7%) was higher than that of IgM RF (71.4%). Anti-CCP was positive in 58.1% in 31 RA patients with negative IgM RF. CONCLUSIONS: The results said that the combination test of anti-CCP with IgM RF might be useful for the diagnosis of RA because of its higher sensitivity and specificity than IgM RF alone.

Anticuerpos anti-CCP en artritis reumatoidea: relación con características clínicas, citocinas Th1/Th2 y HLA-DRB1 / Anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis: relation with clinical features, cytokines and HLA-DRB1

En el presente estudio se examinó la especificidad y la sensibilidad de los anticuerpos antipéptidos citrulinados cíclicos (CCP) en pacientes latinoamericanas con artritis reumatoidea (AR), así como su relación con la actividad de la enfermedad, manifestaciones extraarticulares (MEA), síntesis de citocinas (IL-4, IL-10, IL-12, TNF-µ e IFN-gamma ) y factor reumatoideo (FR) IgM e IgA, y con el polimorfismo del HLA-DRB1. Se examinaron 79 pacientes con AR (69 con AR establecida y 10 con AR temprana sin previo tratamiento), 56 pacientes con espondilitis anquilosante (EA), 25 con lupus eritematoso sistémico (LES), 50 con síndrome de Sjögren primario (SSp) y diez individuos sanos. De las 69 pacientes con AR establecida, 36 fueron reevaluadas 2 años después. La actividad de la AR se examinó según los criterios del Colegio Americano de Reumatología. Los anticuerpos anti-CCP2, el FR y los niveles de citocinas se determinaron mediante inmunoensayo, y la genotipificación del HLA se llevó a cabo por reacción en cadena de la polimerasa utilizando mezclas de iniciadores específicos. Los anticuerpos anti-CCP se observaron en 96% de los pacientes con AR en la primera evaluación y en 86% en la segunda ( p=0,12), sin modificación significativa en los valores (131±58,7 vs. 130,6±67,1 UI). Su sensibilidad y especificidad global fue de 94% y 92%, respectivamente, pero cuando sólo se consideraron los niveles altos (>60 UI) fueron de 84% y 95%, respectivamente. La razón de probabilidades (RP) positiva fue de 12 y la RP negativa de 0,06. El valor predictivo (VP) positivo fue de 87% y el VP negativo de 96%. Los anticuerpos anti-CCP se observaron en 12% de los pacientes con LES y con SSp, en 2% de los de EA y en 10% de los controles sanos. En los pacientes con AR no se asociaron con la actividad de la enfermedad, MEA y alelos del HLA-DRB1. Tampoco se observaron correlaciones significativas entre sus valores y los niveles de citocinas. En conclusión, los anticuerpos anti-CCP tienen un interés diagnóstico para la AR en nuestra población, pero su utilidad en el seguimiento clínico es limitada y su síntesis es independiente del HLA-DRB1 y no se correlacionan con niveles de citocinas Th1/Th2.

The specificity and sensitivity of anti-cyclic citrullinated peptide antibodies (anti-CCP) was examined in Latin-American patients with rheumatoid arthritis (RA). The variables considered included: 1) relation with the activity of disease, 2) extra-articular manifestations (EAM), 3) synthesis of cytokines (IL-4, IL-10, IL-12, TNF-alpha , and IFN-gamma ) and IgM and IgA rheumatoid factor (RF), and 4) the association with HLA-DRB1 polymorphism. Seventy-nine RA patients were assessed (69 with established RA, and 10 with recent-onset RA not receiving any treatment), 56 with ankylosing spondylitis (AS), 25 with systemic lupus erythematosus (SLE), 50 with primary Sjögren’s syndrome (pSS), and 10 healthy individuals. Of the 69 patients with established RA, 36 were reexamined 2 years later. The activity of the RA was measured by criteria adopted by the American College of Rheumatology. Anti-CCP2, RF and cytokines levels were determined by ELISA. HLA genotypes were established by first, PCR sequence amplification using sequence-specific primers and then, complete sequencing of the product. Anti-CCP antibodies were observed in 96% of patients with RA during the first evaluation and in 86% at the second evaluation ( p=0.12). No significant change in antibody titre was observed between the two evaluations (131±58.7 and 130.6±67.1 IU, respectively). The overall sensitivity and specificity was 94% and 92%, respectively; however, at titres >60 IU, the values were 84% and 95%, respectively. The anti-CCP likelihood ratio positive test was 12 and the likelihood ratio negative test was 0.06. The positive predictive value was 87%, and the negative predictive value was 96%. Anti-CCP antibodies were observed in 12% of SLE and pSS patients, in 2% of AS patients, and in 10% of healthy controls. In RA patients, these antibodies were not associated with the activity of disease, EAM or HLA-DRB1 alleles; no significant correlation was observed between antibody titre and cytokines level. Although anti-CCP antibodies have potential as a diagnostic tool for RA, they are not useful for monitoring clinical activity or predicting the clinical course of disease. Antibody synthesis is HLA-DRB1 independent and not correlated with Th1/Th2 cytokines.

Significance of Hidden Rheumatoid Factor IgM,Anti-Cyclic Citrullinated Peptide Antibodies,Antikeratin Antibodies,Combined Test in Diagnosis of Juvenile Idiopathic Arthritis / 实用儿科临床杂志

Objective To explore the significance of hidden rheumatoid factor-IgM(HRF-IgM),anti-cyclic citullinated peptide antibodies(anti-CCP),antikeratin antibodies(AKA)combined test in the diagnosis of juvenile idiopathic arthritis(JIA).Methods The anti-CCP and rheumatoid factors(RF)were tested by enzyme linked immunosorbent assay(ELISA)in serum samples from 60 children with JIA,27 systemic lupus erythematosus(SLE),18 kawaski diseases and 50 healthy children who were enrolled to serve as normal controls.Indirect immumofluorescence method was used to test AKA.Using the QAE-Sephadex-A50 to separate RF then tested HRF-IgM by ELISA.Results Positive anti-CCP were found in sera of 13 patients with JIA(21.7%)and specificity 96.8%.RF were found lower test both with the JIA and other groups(?2=0.17 P=0.68).The results of AKA were similar to the anti-CCP,they were both lower sensitivity and higher specificity.There were 65% sensitivity and 85.3% specificity in the HRF-IgM,and great significant difference in positive rate in JIA and other group(?2=40.22 P=0.0001).Conclusions JIA children in the studied series has a higher detection rate and value of HRF-IgM as compared to the other control groups.HRF-IgM,anti-CCP,AKA combined test in JIA can prove to be a valuable reference index for diagnosing suspected JIA children.

The study of Anti-cyclic citrullinated peptide antibodies and rheumatoid factors with the disease activity of rheumatoid arthritis / 中华风湿病学杂志

Objective To compare the correlation between ACCP, IgA-RF, IgG-RF, IgM-RF and disease activity, bone erosion of rheumatoid arthritis. Method The correlation analysis between ACCP, IgA-RF, IgG-RF, IgM-RF and disease activity score (DAS), Ritchie′s articular index (RAI) were made SPSS software. ACCP, IgA-RF, IgG-RF, IgM-RF were compared between patients with erosive disease and with non-erosive disease. Results IgM-RF was associated with RAI, but ACCP, IgA-RF and IgG-RF were not associated with RAI. The above parameters were not associated with DAS by Spearman correlation analysis. The association between above parameters and bone erosion was not detected, however. Conclusion IgM-RF is associated with disease activity. ACCP and IgA-RF, IgG-RF are not associated with disease activity. No association is found between above parameters and bone erosion.

Anti-mutated citrumnated vimentin antibodies in the diagnosis of rheumatoid arthritis / 中华风湿病学杂志

Objective To determine the diagnostic value of anti-mutated citrullinated vimentin(anti- MCV)antibodies for rheumatoid arthritis(RA).Methods The anti-MCV were determined in 136 patients with RA,80 non-RA patients and 19 normal peoples.The diagnostic value of anti-MCV was assessed and compared with anti-CCP,AKA and RF.Results The sensitivity and specificity of anti-MCV in the 136 RA patients was 95.6% and 80.8% respectively,there was significanl difference between the test group and the control group(P

Diagnostic Role of the Anti-Cyclic Citrullinated Peptide Antibodies in Rheumatoid Arthritis / 대한진단검사의학회지

BACKGROUND: Rheumatoid arthritis (RA) is the most common systemic autoimmune disease; but there are no useful, specific and practicable tests for this diagnosis. We evaluated the diagnostic performance of anti-cyclic citrullinated peptide antibodies (anti-CCP) using ELISA for the diagnosis of RA. METHODS: Anti-CCP (EURO-DIAGNOSTICA, MALMo, Sweden) was determined in serum samples from 114 patients with RA and 202 controls (31 SLE, 40 osteoarthritis, 75 other diseases, and 56 healthy subjects). The Rheumatoid factor (RF) by turbidimetry was also assayed and results were compared to anti-CCP for sensitivity and specificity by the receiver-operating characteristic (ROC) curve. RESULTS: At each optimum cut-off value, the sensitivities of anti-CCP and RF were 68.4% and 66.7% and the specificities were 96% and 84.6%, respectively. RA patients with anti-CCP had a mean antibody concentration of 559.6+/-752.0 U/mL (range, 24 - 4717). Thirteen of 38 (34.2%) sera from RF negative RA patients were positive for anti-CCP. On each ROC curve, the area under the curve was 0.872 (confidence interval, 0.827 - 0.917) for anti-CCP and 0.794 (CI, 0.737 - 0.851) for RF, which showed no statistically significant difference. CONCLUSIONS: We considered that anti-CCP could be a useful test with excellent diagnostic performance for the diagnosis of RA.

Diagnostic Performance of the Anti-Cyclic Citrullinated Peptide Antibodies in Rheumatoid Arthritis / 대한진단검사의학회지

BACKGROUND: The Rheumatoid Factor (RF) is the only serological marker in the diagnosis of rheumatoid arthritis (RA), but its sensitivity and specificity are not satisfactory for the diagnosis of RA. Therefore, we investigated the diagnostic performance of a new anti-cyclic citrullinated peptide antibodies test (anti-CCP) by the enzyme-linked immunosorbent assay (ELISA) in RA. METHODS: A cyclic peptide variant that contains citrulline was used as an antigenic substrate in ELISA. We performed the RF and anti-CCP in 324 RA patients, 251 non-RA patients (rheumatic diseases other than RA), and 286 normal individuals. Diagnostic performances such as sensitivity and specificity were evaluated by the receiver-operator characteristics (ROC) curve at optimal cut-off values. The optimal cut-off values were determined at the maximal point of the area under the curve. RESULTS: The sensitivity and specificity of anti-CCP were 72.8% and 92% at 3.8 U/mL. The sensitivity and specificity of RF were 80.6% and 78.5% at 9 U/mL. The sensitivity and specificity of anti-CCP and RF were 67%, 95.2% and 63.3%, 90% at 8.4 U/mL, 20 U/mL, respectively. A combination of anti-CCP with RF increased the sensitivity and specificity to 79.3%, 96.4%, respectively. Anti-CCP was positive in 23.8% among 63 sero-negative RA patients. CONCLUSIONS: We considered that the anti-CCP might be useful as another new serological marker for the diagnosis of a RA combination with RF, or not, because the anti-CCP has a higher diagnostic specificity than the RF and was an easy, convenient ELISA method in performance.

Diagnostic significance of detection of anti-citrullinated peptide antibodies in juvenile rheumatoid arthritis / 中华风湿病学杂志

Objective To assess the diagnostic value of anti-cyclic citrullinated peptide antibody(an- ti-CCP),rheumatoid factor,anti-perinuclear factor(APF)and anti-keratin antibody(AKA)for juvenile rheumatoid arthritis(JRA)and compare it with rheumatoid arthritis(RA).Methods Anti-CCP was determined by ELISA in 54 serum samples of JRA patients,31 from patients with other rheumatic diseases and 116 RA patients.RF was determined in the same samples by latex agglutination test.APF and AKA were determined by indirect immunofluorescent assay.Results The sensitivity of anti-CCP,RF,APF and AKA was 61.1%, 57.4%,37.0% and 18.5% and their specificity was 96.8%,93.6%,96.8% and 100%,respectively for the diag- nosis of JRA.The sensitivity of anti-CCP resembleed that of RF,Anti-CCP was more sensitivity than APF and AKA in JRA.The sensitivity of anti-CCP,RF,APF and AKA was 82.3%,78.3%,48.7% and 25.4% and their specificity was 95.7%,73.7%,91.6%,94.0% respectively,for the diagnosis of RA.Anti-CCP,RF,APF and AKA were less sensitive in JRA than in RA.There was no statistical significance in specificity of these anti- bodies for the diagnosis of JRA and RA.Conclusion The detection of anti-CCP,RF,APF and AKA are use- ful for the diagnosis of JRA,but are less sensitive than in adults RA.