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Form of tenascin-C may be a susceptibility biomarker for RA
Citrullinated tenascin-C may be a biomarker for active rheumatoid arthritis, and could be present up to 16 years prior to onset of the disease, according to the results of a recently published study.
“We knew that tenascin-C is found at high levels in the joints of people with rheumatoid arthritis. We decided to see if it could be citrullinated and, if so, whether it was a target for the autoantibodies that attack the body in RA,” Anja Schwenzer, postdoctoral research assistant at the Kennedy Research Institute, said in a University of Oxford press release. “That might also indicate whether it could be used in tests to indicate the disease.”
Schwenzer and colleagues examined four cohorts of patients with rheumatoid arthritis (RA) from previous studies, two screening cohorts of 20 British patients with RA and 20 healthy individuals. In addition, data from 101 pre-RA participants and 326 matched control participants were identified in a nested, case-control study in four cohorts in Southern Europe, and 1,185 patients with RA and 160 control individuals from the Swedish, population-based Epidemiological Investigation of RA (EIRA) study were included. Further, 287 patients with RA and 330 control patients with osteoarthritis (OA) from the United States were included.
Following a laboratory citrullination reaction, liquid chromatography–mass spectrometry analyses, enzyme-linked immunosorbent assay (ELISA) and cross-reactivity assays, the researchers found the fibrogen-like globe domain of tenascin-C was citrullinated by recombinant human peptidyl arginine deiminase 2 (rPAD2).
Five tenascin-C peptides were identified using mass spectroscopy, and serum from the 20 patients with RA and healthy individuals were used to map the antibody response by ELISA. Serum from 35% and 40% of patients showed antibodies to two forms of citrullinated tenascin-C, but none were observed in sera from control participants.
In sera from 101 pre-RA participants, 18% of sera were positive for a form of citrullinated tenascin-C compared to 2% of 326 samples from healthy participants. Analysis of sera from the EIRA cohort from 1985 revealed 47% of patients with RA and 2% of control individuals had antibodies to the peptide, and a diagnostic sensitivity of 51% was confirmed in the cohort of 287 patients with RA and 330 patients with OA from the U.S. cohort.
“What is particularly exciting is that when we looked at samples taken from people before their arthritis began, we could see these antibodies to citrullinated tenascin-C up to 16 years before the disease occurred — on average, the antibodies could be found seven years before the disease appeared,” Kennedy Institute's Professor Kim Midwood, BSc(Hons), PhD, said in the release.
Stephen Simpson, PhD, research director for Arthritis Research U.K., said early diagnosis is important. “When it comes to rheumatoid arthritis, early diagnosis is key with research showing that there is often a narrow 'window of opportunity' following the onset of symptoms for effective diagnosis and control of disease through treatment,” Simpson said in the release. “Furthermore, current tests for rheumatoid arthritis are limited in their ability to diagnose disease in different patients. This latest research provides the basis of tests that could improve diagnosis and, importantly, detect disease at a very early stage, with the promise even that people at risk of developing rheumatoid arthritis can be followed before the disease begins.” – by Shirley Pulawski
Disclosure: The researchers report the data are the subject of a patent filing. Please see the full study for a list of all other authors’ relevant financial disclosures.