A study of synovial membranes from patients with rheumatoid arthritis (RA) suggests that the intermediate filament component keratin is altered in patients with this disease.
“Citrullinated keratin might be involved in the pathogenesis of RA, including abnormal cell proliferation, apoptosis and autoimmunity, although the exact mechanism remains unclear,” report Xiaotian Chang (Shandong Academy of Medical Sciences, China) and co-workers.
The enzyme that converts arginine to citrulline has been demonstrated in patients with RA and citrullinated proteins are involved in RA development, the team explains.
To investigate the role of keratin in RA, the team examined synovial membranes from 12 RA patients and 28 osteoarthritis (OA) patients.
Immunohistochemistry demonstrated the presence of keratin in all the RA patients, but in only 20 of the OA patient samples at lower levels.
Double immunofluorescent staining of the RA synovial tissue revealed citrullination occurred mainly in the cells lining the RA synovial membrane and other RA synovial tissue.
This suggests the “possibility that citrullinated keratin might change its functional properties and consequently contribute to abnormal cell differentiation or irregular apoptosis, two important features of the diseased tissue,” say Chang et al.
Furthermore, the citrulline concentration in RA samples was most intense on the outside of the membrane and co-located with cytokeratin; in contrast, the citrulline concentration in the OA samples was greatest inside the membrane.
“The differential tissue distribution suggests that keratin may play differential roles for the two diseases,” Chang et al conclude in the journal Rheumatology International.