In the rheumatoid pannus, anti-filaggrin autoantibodies are produced by local plasma cells and constitute a higher proportion of IgG than in synovialfluid and serum

IgG anti-filaggrin autoantibodies (AFA) are the most specific serological m arkers of rheumatoid arthritis (RA). They include the so-called 'anti-kerat in antibodies' (AKA) and anti-perinuclear factor (APF), and recognize human epidermal filaggrin and other (pro)filaggrin-related proteins of various e pithelial tissues. In this study we demonstrate that AFA are produced in rh eumatoid synovial joints. In 31 RA patients, AFA levels were assayed at equ al IgG concentrations in paired synovial fluids (SF) and sera. AFA titre-li ke values determined by indirect immunofluorescence and immunoblotting and AFA concentrations determined by ELISA were non-significantly different in serum and SF, clearly indicating that AFA are not concentrated in SF. In co ntrast, we demonstrated that AFA are enriched in RA synovial membranes, sin ce the ELISA-determined AFA in low ionic-strength extracts of synovial tiss ue from four RA patients represented a 7.5-fold higher proportion of total IgG than in paired sera. When small synovial tissue explants from RA patien ts were cultured for a period of 5 weeks, the profile of IgG and AFA releas ed in the culture supernatants was first consistent with passive diffusion of the tissue-infiltrating IgG (including AFA) over the first day of cultur e, then with a de novo synthesis of IgG and AFA. Therefore, AFA-secreting p lasma cells are present in the synovial tissue of RA patients and AFA can r epresent a significant proportion of the IgG secreted within the rheumatoid pannus.