Discovering the citrullinated protemome in rheumatoid joints
Helse Sør has provided co-funding for a mass spectrometer required in the project. As full funding is not available yet, the instrument could not be acquired so far. - A new technology for enrichment of citrullinated peptides was developed.The projects aims to identify the citrullinated proteins present in the inflamed joints of rheumatoid arthritis (RA) patients. Citrullinated proteins derive from an enzymatic modification (deimination) of the amino acid arginine. Strikingly, RA patients develop autoantibodies reacting with such modified proteins. However, current knowledge on the nature of the citrullinated proteins present in the inflamed joints and on the targets of the autoantibodies is very limited. The mass spectrometer (ion trap instrument equipped with electron transfer dissociation) applied for in the project has not been acquired yet. Helse Sør has provided co-funding, but full financing is not available yet. Further attempts are made to realize the acquisition. The project also requires techniques for the specific enrichment of citrullinated peptides and proteins. There has been substantial progress on that part. We developed a method which enables a highly specific enrichment of citrullinated peptides from very heterogeneous mixtures. It has been successfully applied to fish out citrullinated peptides from synovial fluid of RA patients. The technology has resulted in filing of a patent application and there are ongoing license negotiations (by Birkeland Innovation, the technology transfer office at the University of Oslo). Due to the patenting process the results could not be published in 2007. This is currently in progress. We can now specifically fish out the citrullinated proteome from the joints of RA patients and the described mass spectrometer will allow the identification of the proteins. The instrument will be acquired as soon as funding is complete.
Holm A, Tutturen A, Fleckenstein B
Methods for modifying, isolating, detecting, visualizing, and quantifying citrullinated peptides, polypeptides and proteins
United States Provisional Patent Application. Filed with the U.S. Patent & Trademark Office, 2007