Prevalence and significance of isotypes of anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis

Syed, Reema; Gilliam, Brooke E; Moore, Terry L.

doi:10.1136/ard.2007.084855

Cited by 19 publications

(17 citation statements)

References 6 publications

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“…Measurement of all 3 anti-CCP antibody isotypes has been suggested in both RA [10] and JIA [11]. Verpoort et al [10] found that undifferentiated arthritis patients who were positive for both IgA and IgM anti-CCP antibodies were more likely to develop RA than those with IgG anti-CCP antibodies alone.…”

Section: Discussionmentioning

confidence: 99%

“…A third generation anti-CCP antibody test, the QUANTA Lite CCP3 ELISA (Inova Diagnostics, Inc., San Diego, CA), was used for the detection of IgG anti-CCP antibodies according to the manufacturer's instructions. The cut-off value for a positive result was 20 U. IgA and IgM anti-CCP antibodies were measured by ELISA (QUANTA Lite CCP3 ELISA, Inova Diagnostics, San Diego, CA) as previously described [11]. Cut-off values for a positive result were calculated at optical density (OD) = 0.16 and OD = 0.43, respectively, determined as the mean plus two standard deviations (SD) of a healthy population from a previous study [11].…”

Section: Methodsmentioning

confidence: 99%

“…The cut-off value for a positive result was 20 U. IgA and IgM anti-CCP antibodies were measured by ELISA (QUANTA Lite CCP3 ELISA, Inova Diagnostics, San Diego, CA) as previously described [11]. Cut-off values for a positive result were calculated at optical density (OD) = 0.16 and OD = 0.43, respectively, determined as the mean plus two standard deviations (SD) of a healthy population from a previous study [11]. Clinical data regarding signs of active disease (including joint pain and swelling, limitations of range of motion, fever, rash, visceral involvement, and inflammatory markers) were collected from patient records of the Pediatric Rheumatology clinics.…”

Section: Methodsmentioning

confidence: 99%

“…Several studies have noted the significance of measuring anti-CCP antibodies in JIA as an important indicator for destructive disease, as is the case in RA [3-9]. Recently, the identity of various immunoglobulin isotypes of anti-CCP antibodies has also been reported in RA [10] and JIA [11]. These studies revealed that a varied pattern of isotype usage early in disease was possibly associated with aggressive disease, especially when all three isotypes (IgG, IgA, and IgM) were present [2,10,11].…”

Section: Introductionmentioning

confidence: 99%

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Evidence of fibrinogen as a target of citrullination in IgM rheumatoid factor-positive polyarticular juvenile idiopathic arthritis

et al. 2011

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BackgroundSeveral studies have noted the significance of measuring anti-cyclic citrullinated peptide (CCP) antibodies in juvenile idiopathic arthritis (JIA) as an important indicator for destructive disease, as is the case in rheumatoid arthritis (RA). While the role of anti-CCP antibodies in RA and JIA has become better understood, the identity of the target proteins of this modification has remained elusive. In this study, we evaluated serum from patients with various subtypes of JIA to investigate the presence of anti-deiminated (citrullinated) fibrinogen and anti-citrullinated α-enolase antibodies, and their association with RF and anti-CCP antibody isotypes.MethodsSera were obtained from 96 JIA patients, 19 systemic lupus erythematosus (SLE) patients, and 10 healthy children. All sera were measured for antibodies against citrullinated and native fibrinogen and α-enolase by an enzyme linked immunosorbent assay (ELISA). In addition, all sera were assayed for anti-CCP antibody isotypes and rheumatoid factor (RF) isotypes by ELISA. The relationship between anti-citrullinated fibrinogen and anti-α-enolase antibodies and disease activity and joint damage were also investigated. All results were correlated with clinical and laboratory parameters using Spearman's rho correlation coefficient. Multiple logistic regression analysis was utilized to identify which variables were associated with joint erosions and diagnosis of JIA.ResultsThirty-one JIA patients (32%) demonstrated reactivity to citrullinated fibrinogen and 9 (9%) to citrullinated α-enolase. Reactivity to citrullinated fibrinogen and α-enolase was predominantly found in IgM RF-positive polyarthritis patients. Fourteen JIA patients reacted with native α-enolase and a higher percentage of SLE patients reacted with citrullinated α-enolase when compared to JIA patients. Anti-citrullinated fibrinogen antibodies correlated with the presence of IgG anti-CCP antibodies and IgA and IgM RF. The presence of anti-citrullinated α-enolase antibodies correlated with IgA anti-CCP antibodies. IgG anti-CCP antibodies were significantly associated with joint damage and anti-citrullinated fibrinogen antibodies were strongly associated with JIA when compared to control groups. Anti-citrullinated fibrinogen antibodies demonstrated high sensitivity (81%) for IgM RF-positive polyarticular JIA. IgG anti-CCP antibodies had the highest specificity (95%) for JIA, with anti-citrullinated fibrinogen antibodies, IgA anti-CCP antibodies and IgA RF all following at 84%.ConclusionsJIA patient sera exhibited strong reactivity to anti-citrullinated fibrinogen antibodies and demonstrated high sensitivity and specificity for JIA, primarily in IgM RF-positive polyarthritis patients. Fibrinogen is one of several protein targets for citrullination in JIA.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evidence of fibrinogen as a target of citrullination in IgM rheumatoid factor-positive polyarticular juvenile idiopathic arthritis

et al. 2011

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“…The authors' research has also shown that IgG anti-CCP antibodies demonstrated a high specificity for JIA (94.7%), and also specifically in patients with polyarticular disease resembling adult RA (93.9%) [42]. The authors have also evaluated isotypes of anti-CCP antibodies (IgG, IgA and IgM) in JIA patients and our continued work in identifying target proteins of the citrulline modification has identified anti-citrullinated fibrinogen as a target in IgM RF-positive polyarticular JIA [42,43].…”

Section: Expert Opinionmentioning

confidence: 88%

The role of anti-cyclic citrullinated peptide (CCP) antibodies in early detection of rheumatoid arthritis: an overview of the INOVA Diagnostics, Inc. QUANTA Lite CCP assays

Gilliam

Moore

2012

Expert Opinion on Medical Diagnostics

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Antibodies to Cyclic Citrullinated Peptides in Patients With Juvenile Idiopathic Arthritis and Patients With Rheumatoid Arthritis: Shared Expression of the Inherently Autoreactive 9G4 Idiotype

Peckham

Cambridge

Bourke

et al. 2017

Arthritis & Rheumatology

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In healthy individuals, 9G4-positive B cells comprise 5-10% of the peripheral blood pool but serum immunoglobulins utilizing V 4-34 are disproportionately low. The idiotope recognized by 9G4 was detected on anti-CCP antibodies in >80% of patients with RF-positive polyarticular JIA. V 4-34 usage by anti-CCP in both JIA and RA patients suggest elicitation of these autoantibodies through shared pathogenic B cell selection processes.

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Prevalence and significance of isotypes of anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis

Cited by 19 publications

References 6 publications

Evidence of fibrinogen as a target of citrullination in IgM rheumatoid factor-positive polyarticular juvenile idiopathic arthritis

Evidence of fibrinogen as a target of citrullination in IgM rheumatoid factor-positive polyarticular juvenile idiopathic arthritis

The role of anti-cyclic citrullinated peptide (CCP) antibodies in early detection of rheumatoid arthritis: an overview of the INOVA Diagnostics, Inc. QUANTA Lite CCP assays

Antibodies to Cyclic Citrullinated Peptides in Patients With Juvenile Idiopathic Arthritis and Patients With Rheumatoid Arthritis: Shared Expression of the Inherently Autoreactive 9G4 Idiotype

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