title: Quantification of IFNγ- and IL17-producing cells after stimulation with citrullinated proteins in healthy subjects and RA patients.
abstract: Antibodies against citrullinated proteins are highly specific for rheumatoid arthritis (RA) and are currently used as a diagnostic marker. In this study, we wanted to quantify the numbers of T cells that react to a wide range of citrullinated proteins in a wide range of HLA-DR subtypes in order to investigate whether citrullination might create T-cell neo-epitopes and could initiate a universal T-cell response. Therefore, PBMCs from healthy volunteers and RA patients were stimulated with a citrullinated and non-citrullinated cell extract on IFNγ-ELISpot. We found a significantly higher number of IFNγ-secreting cells after stimulation with citrullinated proteins compared to non-citrullinated proteins in RA patients (1:14,441 cells vs. 1:32,880 cells) as well as in healthy subjects (1:6,261 reactive cells compared to 1:16,212 cells). Additionally, a higher number of IL17-secreting cells were found after stimulation with citrullinated proteins compared to their non-citrullinated counterparts. Our data indicate that citrulline-dependent T-cell response is not restricted to RA patients but that citrullination as such gives rise to a universal break in tolerance.
authors: Laboratory for Pharmaceutical Biotechnology, Ghent University, Harelbekestraat 72, 9000, Ghent, Belgium.
authors: Katleen
authors: K
authors: Van Steendam
authors: Marlies
authors: M
authors: De Ceuleneer
authors: Kelly
authors: K
authors: Tilleman
authors: Dirk
authors: D
authors: Elewaut
authors: Filip
authors: F
authors: De Keyser
authors: Dieter
authors: D
authors: Deforce
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism*; D002956:Citrulline / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D002956:Citrulline; D007371:Interferon-gamma