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Citrullinated Peptides as a Substrate for the Detection of Rheumatoid Arthritis-Specific Autoantibodies
Arthritis Research & Therapy volume 1, Article number: S26 (1999)
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The diagnosis of rheumatoid arthritis (RA) depends primarily on the clinical manifestation of the disease. The only serologic test routinely used is the determination of the presence of rheumatoid factors in the serum. However, these antibodies are also present in relatively high percentages in other autoimmune and infectious diseases and in up to 15% of healthy individuals. Antibodies of a more specific nature were first described by Nienhuis and Mandema [1], who discovered that RA sera specifically label the 'perinuclear factor', a component of the keratohyaline granules in buccal mucosa cells. These antiperinuclear factor (APF) antibodies are reported to be present in 49–91% of RA patients, with a specificity of over 70%. Due to technical reasons, the APF test never became very popular.
We discovered that APF-directed autoantibodies in RA specifically recognise citrullinated residues in polypeptides [3] and developed an ELISA procedure using a single cyclic citrullinated peptide (CCP) as substrate. Our studies showed that the anti-CCP ELISA assay was positive in about 70% of RA sera, with a specificity of more than 98% against disease controls (n > 700). Other studies, which will be presented, corroborate the extreme diagnostic specificity of this auto-antibody for RA. Therefore, we expect that a serologic test based on our peptides will be a valuable addition to RA diagnostics and a help in the decisions to be made concerning the treatment of early RA patients.
References
- 1.
Nienhuis RLF, Mandema EA: A new serum factor in patients with rheumatoid arthritis. The antiperinuclear factor. Ann Rheum Dis . 1964, 23: 302-305.
- 2.
Hoet RM, Boerbooms AMTH, Arends M, Ruiter DJ, van Venrooij WJ: Antiperinuclear factor, a marker autoantibody for rheumatoid arthritis: colocalisation of the perinuclear factor and profilaggrin. Ann Rheum Dis. 1991, 50: 611-618.
- 3.
Schellekens GA, de Jong BAW, van den Hoogen FHJ, van de Putte LBA, van Venrooij WJ: Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest. 1998, 101: 273-281.
- 4.
Girbal-Neuhauser E, et al: The epitopes targeted by the rheumatoid arthritis-associated autoantibodies are post-translationally generated on various sites of (pro)filaggrin by deimination of arginine residues. J Immunol. 1999, 162: 585-594.
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van Venrooij, W.J. Citrullinated Peptides as a Substrate for the Detection of Rheumatoid Arthritis-Specific Autoantibodies. Arthritis Res Ther 1, S26 (1999). https://doi.org/10.1186/ar40
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Keywords
- Rheumatoid Arthritis
- Rheumatoid Arthritis Patient
- Serologic Test
- Citrullinated
- Buccal Mucosa
