Antibodies against cyclic citrullinated peptide are associated with HLA–DR4 in simplex and multiplex polyarticular‐onset juvenile rheumatoid arthritis

Ferucci, Elizabeth D.; Majka, Darcy S.; Parrish, L. A.; Moroldo, Marta B.; Ryan, Mary; Passo, Murray H.; Thompson, Susan D.; Deane, Kevin D.; Rewers, Marian; Arend, William P.; Glass, David N.; Norris, Jill M.; Holers, V. Michael

doi:10.1002/art.20773

Cited by 78 publications

(51 citation statements)

References 23 publications

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“…Studies in humans have shown that anti-CCP antibody production precedes the onset of RA and are associated with the presence of DR4 (20,21). The DR4-transgenic mice described herein were shown to produce RFs as well as anti-CCP antibodies.…”

Section: Discussionmentioning

confidence: 60%

New humanized HLA–DR4–transgenic mice that mimic the sex bias of rheumatoid arthritis

Taneja¹,

Behrens²,

Mangalam³

et al. 2007

Arthritis & Rheumatism

100

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Objective. To generate a mouse model that can mimic human rheumatoid arthritis (RA). A major difference between RA in humans and collagen-induced arthritis (CIA) in mice is the lack of sex bias and autoantibodies in the animal model. We used DRB1*0401-transgenic mice to understand the role of DR4 in susceptibility and sex bias in RA.Methods. A transgenic mouse was generated that lacked all endogenous mouse class II genes (AE o ) and expressed the RA susceptibility allele HLA-DRB1*0401. These transgenic mice were tested for incidence, severity, and sex distribution of CIA.Results. DRB1*0401.AE o mice developed CIA predominantly in females and produced rheumatoid factors, similar to the features of human RA. Another feature similar to human RA is the expression of class II molecules on antigen-presenting cells as well as T cells. Activated and sorted CD4؉ T cells can present DR4-restricted type II collagen (CII)-derived peptide in vitro, but cannot process the antigen. This suggests a role for these cells in epitope presentation locally in joints, which affects disease severity. After challenge with CII, female mice had higher cellularity and increased T cell proliferation and produced higher levels of proinflammatory cytokines than did the male mice.Conclusion. DR4.AE o mice expressed HLA similar to humans and displayed increased arthritis susceptibility in females, thus mimicking RA in humans. This model may be valuable for studying sex differences observed in humans and for understanding why autoimmunity is increased in women. These mice may also be useful for developing future therapeutic strategies.

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Section: Discussionmentioning

confidence: 60%

New humanized HLA–DR4–transgenic mice that mimic the sex bias of rheumatoid arthritis

Taneja¹,

Behrens²,

Mangalam³

et al. 2007

Arthritis & Rheumatism

100

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“…Ao contrário do FR, a dosagem do anti-CCP possui uma elevada especificidade, superior a 90%, especialmente quando presente um título elevado (7) . O anti-CCP está raramente presente em outras doenças reumatológicas (16,20,(24)(25)(26)(27)(28) . Em nossa casuística, observamos que 2,3% (9/386) dos pacientes-controle apresentavam reatividade para o anti-CCP, sendo 0,2% (1/386) nos controles saudáveis e 2,1% (8/386) nos controles doentes.…”

Section: Discussionunclassified

Valor diagnóstico do anticorpo antipeptídeo citrulinado cíclico na artrite reumatóide

Silva¹,

Matos²,

Lima³

et al. 2006

Rev. Bras. Reumatol.

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Introdução: a artrite reumatóide (AR) é considerada uma das doenças auto-imunes mais freqüentes, mas um teste viável e específico para seu diagnóstico não está disponível. Objetivos: avaliar a eficiência diagnóstica de um novo teste comercial realizado pela técnica de ELISA (Immunoscan RA; EuroDiagnostica), que detecta o anticorpo antipeptídeo citrulinado cíclico (anti-CCP), para o diagnóstico da AR. Métodos: anticorpo anti-CCP e fator reumatóide (FR) foram pesquisados no soro de 486 pacientes: 100 pacientes com AR e 386 controles, incluindo indivíduos normais, pacientes com outras doenças reumáticas e não-reumáticas, bem como pacientes com doenças infecciosas. Avaliação comparativa do desempenho diagnóstico dos testes foi feita mediante cálculo dos diversos índices diagnósticos e da curva ROC (receiver operator characteristic). A análise estatística foi feita utilizando os testes do qui-quadrado, exato de Fisher e Mann-Whitney. Resultados: ao ponto de corte de 25 UI/ml, o anti-CCP apresentou sensibilidade de 68% (IC 95%, 57,8-76,8%), especificidade de 97,7% (IC 95%, 95,5-98,8%), valor preditivo positivo (VPP) de 88,3% (IC 95%, 78,5-94,2%), valor preditivo negativo (VPN) de 92,2% (IC 95%, 89-94,5%) e razão de verossimilhança (RV) de 29,2% (IC 95%, 15,1-56,4%). Os pacientes com AR anti-CCP positivos apresentavam titulação média igual a 920,7 UI/ml (variação, 70,5-2000 UI/ml). Pacientes não-reumatóides anti-CCP positivos apresentavam titulação média de 38,7 UI/ml (variação,29,4 UI/ml , Afonso Napoleão Matos, Áurea Maria Santana Lima, Elízia Fernandes Lima (4) , Antônio Pinheiro Gaspar (5) , José Antônio Fortes Braga (6) , Edgar M. Carvalho AbStRAct Introduction: Rheumatoid arthritis (RA) is one of the most common autoimmune rheumatic diseases, but a specific and reproducible test for its diagnosis is still lacking. Objectives: To evaluate the diagnostic efficiency of a new commercial ELISA kit in detecting anti-cyclic citrullinated peptide antibodies (anti-CCP) for the diagnosis of RA. Methods: Anti-CCP antibodies and rheumatoid factor (RF) were determined in the serum of 486 patients: 100 patients with RA and 386 controls, including healthy subjects, patients with other non-rheumatic and rheumatic disease, as well as patients with infections disease. Comparative evaluation of diagnostic performance of anti-CCP and RF was done by calculation the several diagnostic indexes and construction of the ROC (receiver operator characteristic) curve. Statistical analysis included chi-square, Fisher exact, and Mann-Whitney's test. Results: At cutoff of 25 UI/ml, anti-CCP showed sensitivity of 68% (95% CI, 57,8-76,8%), specificity of 97,7% (95% CI, 95,5-98,8%), positive predictive value (VPP) of 88,3% (95% CI, 78,5-94,2%), negative predictive value (VPN) of 92,2% (95% CI, 89-94,5%) and likelihood ratios (LR) of 29,2% (95% CI, 15,1-56,4%). Anti-CCP-positive RA patients had a mean antibody concentration of 920,7 UI/ml (range, 70,5-2000 UI/ml). Anti-CCP-positive non-RA patients had a mean antibody concentration of 38,7 UI/ml (ra...

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“…van Rossum et al (2003) reported radiological damage in 80% of anti-CCP-positive JIA patients. Anti-CCP was strongly associated with erosive disease at an OR of 14.3 in a large cohort of JIA children including 77 polyarticular and 153 pauciarticular or systemic-onset JIA cases (Ferucci et al, 2005). Detection of anti-CCP was helpful for identifying RF-negative JIA patients and pediatric JIA patients who will need further care as adults (Bacos et al, 2014;Sparchez et al, 2015).…”

Section: Discussionmentioning

confidence: 94%

“…Recent studies have evaluated the role of anti-CCP in JIA in diagnosis and prediction of disease outcome and found that anti-CCP can be detected mainly in patients with polyarthritic onset and who are RF positive (Avcin et al, 2002;Ferucci et al, 2005;Dewint et al, 2006;Syed et al, 2008). Although these ACPAs have similar sensitivities and specificities in diagnosing RA, because they differ in terms of the antigen source, their patterns of reactivity are not completely identical in the same patients, and little data have been obtained about ACPAs other than anti-CCP in JIA.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic performance of anti-citrullinated protein/peptide antibodies in juvenile idiopathic arthritis

et al. 2016

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ABSTRACT. The prevalence rates of anti-citrullinated protein/peptide antibodies (ACPAs) were investigated in a cohort of juvenile idiopathic arthritis (JIA) patients, and their diagnostic performances were compared. ACPAs, including anti-cyclic citrullinated peptide IgG (anti-CCP), anti-CCP IgG/IgA (anti-CCP3.1), citrullinated recombinant rat filaggrin antibodies (CPA), anti-mutated citrullinated vimentin (anti-MCV), and antibodies to citrullinated human IgG-derived peptides (RA/CP), were measured in the sera from 81 JIA patients. Serum samples from 55 children with other joint diseases or viral infections and 49 healthy donors were tested as controls. Of the 81 JIA patients, 7 (8.6%), 8 (9.9%), 17 (21.0%), 23 (28.4%), and 18 (22.2%) were found to be positive for anti-CCP, anti-CCP3.1, CPA, anti-MCV, and RA/CP, respectively, with specificities of 98.1, 95.1, 93.3, 84.6, and 86.5%. Analysis by subtype revealed that 7/7 (100%) of RF-positive polyarticular JIA patients tested positive at high serum levels for anti- MCV or RA/CP, and 5/7 (71.4%) were positive for anti-CCP, anti-CCP3.1, or CPA (P < 0.001, compared with controls). Eighteen of 81 JIA patients demonstrated joint erosions on radiographs and erosive arthritis occurred more often in ACPAs positive patients (P < 0.01). Our findings indicate that although ACPAs are not satisfactory screening biomarkers for JIA due to low sensitivity, ACPA measurement can aid in diagnosing RF-positive polyarticular JIA and identifying JIA patients with severe bone involvement. The diagnostic performance of each ACPA in JIA is different, and the careful selection of assays is necessary.

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Antibodies against cyclic citrullinated peptide are associated with HLA–DR4 in simplex and multiplex polyarticular‐onset juvenile rheumatoid arthritis

Cited by 78 publications

References 23 publications

New humanized HLA–DR4–transgenic mice that mimic the sex bias of rheumatoid arthritis

New humanized HLA–DR4–transgenic mice that mimic the sex bias of rheumatoid arthritis

Valor diagnóstico do anticorpo antipeptídeo citrulinado cíclico na artrite reumatóide

Diagnostic performance of anti-citrullinated protein/peptide antibodies in juvenile idiopathic arthritis

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