Japanese Discover Highly Specific Biomarker for RA

Japanese researchers have identified a novel, highly specific biomarker for rheumatoid arthritis (RA). The new biomarker is citrullinated ITIH4 protein.

According to the University of Tsukuba, where the discovery was made, “Most RA patients are positive for anti-citrullinated protein antibodies (ACPA), and these antibodies are highly specific for RA diagnosis.”

“ACPA recognizes various citrullinated proteins, such as fibrinogen, vimentin and glucose- 6-phosphate isomerase. Citrullinated proteins are proteins that have the amino acid arginine converted into the citrulline, which is not one of the 20 standard amino acids encoded by DNA in the genetic code. Autoreactivity to citrullinated protein may increase susceptibility to RA.”

“We examined serum citrullinated proteins from pGIA by western blotting, and the sequence was identified by mass spectrometry. With the same methods, we also analyzed serum citrullinated proteins in patients with RA, primary Sjögren’s syndrome, systemic lupus erythematosus, and osteoarthritis as well as in healthy subjects,” study corresponding author Isao Matsumoto, M.D., Ph.D., explained.

“In patients with RA, we also evaluated the relationship between the expression of the identified protein inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) and clinical features and compared the levels of citrullinated ITIH4 before and after biological treatment.”

Dr. Matsumoto told OTW, “While many candidate citrullinated antigens have been identified in RA joints, the involvement of citrullinated proteins in blood serum remains mostly uninvestigated.”

“And a specific biomarker, especially fluctuated parallel in disease progression in RA, was not confirmed yet. Also, citrullinated antigens are likely to react to anti-citrullinated protein antibody (ACPA), but ACPA was not changed in parallel with disease activity. Thus, we would like to investigate the relevance of citrullinated antigen in arthritis in joints and serum.”

“Notably in sera, we demonstrated that the increase of specific citrullinated protein as citrullinated ITIH4, fluctuated with the arthritis score. Also, in RA patients, citrullinated ITIH4 levels were specifically increased in sera, and significantly correlated with disease activity.”

“Citrullinated ITIH4 in serum could be a novel biomarker to distinguish RA from other rheumatic diseases, and to assess the disease activity in patients with RA. In seronegative (rheumatoid factor negative and ACPA negative) RA patients, this biomarker is possible to distinguish RA and other arthritic disorders. We need to know the function of citrullinated ITIH4 in arthritic joints in the future.”