Antiperinuclear factor, a marker autoantibody for rheumatoid arthritis: colocalisation of the perinuclear factor and profilaggrin.

Hoet, Rene; Boerbooms, A. M. T.; Arends, Maarten; Ruiter, Dirk J.; Venrooij, Walther J. van

doi:10.1136/ard.50.9.611

Cited by 88 publications

(64 citation statements)

References 40 publications

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“…Rheumatoid factor was determined by the standard latex agglutination technique (Dade Behring, Marburg, Germany). APF was determined by indirect immunofluorescence in buccal mucosa cells from a single "positive" donor according to the standard technique (19). Anti-cyclic citrullinated peptide (CCP) antibodies were determined by ELISA (Shield-axis, England) according to manufacturer instructions, with a cut-off of 20 AU/mL.…”

Section: Methodsmentioning

confidence: 99%

Antibodies to citrullinated peptides are not associated with the rate of joint destruction in patients with a well-established diagnosis of rheumatoid arthritis

Nieto-Colonia

Santos

Keusseyan

et al. 2008

Braz J Med Biol Res

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Section: Methodsmentioning

confidence: 99%

Antibodies to citrullinated peptides are not associated with the rate of joint destruction in patients with a well-established diagnosis of rheumatoid arthritis

Nieto-Colonia

Santos

Keusseyan

et al. 2008

Braz J Med Biol Res

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“…The occurrence of ACPAs early in the disease course and even before the onset of clinical symptoms (7,8), as well as the correlation with disease severity and prognosis (9,10), suggests that ACPAs are not only valuable clinical biomarkers but are also pathophysiologically involved in the disease. However, epithelial (pro)filaggrin, which is the first identified antigenic target of ACPAs (11)(12)(13), is not expressed in the joint and RA does not affect filaggrin-containing epithelial tissues, such as skin and buccal mucosa. Based on crucial observations that ACPAs can be produced locally in the joint (14) and that posttranslational modification of arginine into citrulline residues in the context of specific amino acid sequences is essential for recognition by ACPAs (15)(16)(17), the assumption was made that citrullinated filaggrin could be a cross-reacting in vitro antigen rather than a genuine in vivo antigenic target of ACPAs and, subsequently, that distinct citrullinated proteins present in the inflamed synovium may be involved in the induction or perpetuation of the RA-specific humoral autoimmune responses.…”

mentioning

confidence: 99%

Synovial intracellular citrullinated proteins colocalizing with peptidyl arginine deiminase as pathophysiologically relevant antigenic determinants of rheumatoid arthritis–specific humoral autoimmunity

Rycke¹,

Nicholas²,

Cantaert³

et al. 2005

Arthritis & Rheumatism

118

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Objective. To address the ongoing debate concerning the specificity of synovial citrullinated proteins for rheumatoid arthritis (RA) and to analyze their pathophysiologic relevance to the induction or perpetuation of the RA-specific anti-citrullinated protein antibodies (ACPAs).Methods. Synovium of 19 RA patients and 19 non-RA controls was immunostained for the presence of citrullinated proteins with a mouse monoclonal antibody (F95), for the citrullinating enzyme peptidyl arginine deiminase type 2 (PAD-2), and for the free citrulline-producing enzyme inducible nitric oxide synthase (iNOS). Extending the RA cohort to 61 patients, the findings of anticitrulline staining in synovium were related to serum and synovial fluid ACPA levels, as measured by enzyme-linked immunosorbent assay.Results. F95 staining indicated the presence of synovial intracellular citrullinated proteins in 53% of RA samples versus 5% of control samples, whereas extracellular staining was not RA specific. Immunoblotting and inhibition experiments confirmed that the antibody recognized citrullinated proteins but not free citrulline. Accordingly, iNOS was equally found in RA and control synovium and in intracellular citrullinated protein-positive and intracellular citrullinated proteinnegative samples. In contrast, intracellular citrullinated proteins colocalized with PAD-2, which was found in 59% of RA samples versus 17% of control samples. Independent of local disease activity, the presence of the RA-specific synovial intracellular citrullinated proteins was associated with significantly higher systemic and local ACPA levels and with local ACPA production in the joint.Conclusion. These data confirm the presence of RA-specific intracellular citrullinated proteins in synovium. The link with PAD-2 and local and systemic ACPA levels emphasizes their pathophysiologic relevance for RA-specific humoral autoimmunity.

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“…Other autoantibody-antigen systems described in RA are RA33 (3), Sa (4), p68 (5), calpastatin (6), and perinuclear factor (7)(8)(9). Anti-RA33 antibodies, however, are also found in about one-third of systemic lupus erythematosus and mixed connective tissue disease (MCTD) patients (1) and, thus, are not very specific for RA.…”

mentioning

confidence: 99%

“…Reasons for this restraint were the subjective and laborious immunofluorescence technique, the necessity to use preselected buccal cell donors, and the problematic interlaboratory standardization (8). Hoet and coworkers (9) described colocalization of APF with a monoclonal antibody specific for the protein (pro)filaggrin in buccal mucosa cells. This finding was confirmed and extended by the biochemical characterization of (pro)filaggrin as the antigen in the APF test and the related so-called antikeratin antibody (AKA) test (12,13), and the APF/ AKA antibodies are therefore more correctly referred to as "antifilaggrin" antibody.…”

mentioning

confidence: 99%

The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide

Schellekens

Visser

Jong

et al. 2000

Arthritis & Rheumatism

1,252

812

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Objective. Since modern treatment of rheumatoid arthritis (RA) is shifting toward aggressive antirheumatic therapy in an early phase of the disease, diagnostic tests with high specificity are desirable. A new serologic test (anti-cyclic citrullinated peptide [anti-CCP] enzyme-linked immunosorbent assay [ELISA]) was developed to determine the presence of antibodies directed toward citrullinated peptides, using a synthetic peptide designed for this purpose.Methods. A cyclic peptide variant that contains deiminated arginine (citrulline) was designed and used as antigenic substrate in ELISA. Test parameters and diagnostic characteristics of the test were studied in patients with and without RA, in patients with various infectious diseases, and in a group of patients from an early arthritis clinic (EAC).Results. Using prevalent RA and non-RA sera, the anti-CCP ELISA proved to be extremely specific (98%), with a reasonable sensitivity (68%). Also, in the EAC study group, the anti-CCP ELISA appeared to be highly specific for RA (96%). In comparison with the IgM rheumatoid factor (IgM-RF) ELISA, the anti-CCP ELISA had a significantly higher specificity (96% for CCP versus 91% for IgM-RF; P ‫؍‬ 0.016) at optimal cut-off values. The sensitivity of both tests for RA was moderate: 48% and 54% for the anti-CCP ELISA and the IgM-RF ELISA, respectively (P ‫؍‬ 0.36). Combination of the anti-CCP and the IgM-RF ELISAs resulted in a significantly higher positive predictive value of 91% (P ‫؍‬ 0.013) and a slightly lower negative predictive value of 78% (P ‫؍‬ 0.35) as compared with the use of the IgM-RF ELISA alone. The ability of the 2 tests performed at the first visit to predict erosive disease at 2 years of followup in RA patients was comparable (positive predictive value 91%).Conclusion. The anti-CCP ELISA might be very useful for diagnostic and therapeutic strategies in RA of recent onset.

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Antiperinuclear factor, a marker autoantibody for rheumatoid arthritis: colocalisation of the perinuclear factor and profilaggrin.

Cited by 88 publications

References 40 publications

Antibodies to citrullinated peptides are not associated with the rate of joint destruction in patients with a well-established diagnosis of rheumatoid arthritis

Antibodies to citrullinated peptides are not associated with the rate of joint destruction in patients with a well-established diagnosis of rheumatoid arthritis

Synovial intracellular citrullinated proteins colocalizing with peptidyl arginine deiminase as pathophysiologically relevant antigenic determinants of rheumatoid arthritis–specific humoral autoimmunity

The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide

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