Anticytoskeletal autoantibody development in adjuvant arthritis

Because the presence of autoantibodies against cell components is a common feature of most autoimmune diseases and some of these autoantibodies have been detected in sera of patients with rheumatic diseases such as rheumatoid arthritis (RA), we studied the presence of autoantibodies to cell components in an experimental model of chronic inflammation in rats, adjuvant arthritis (AA), to determine possible similarities between AA and human RA.

Sera from arthritic rats were initially tested by indirect immunofluorescence using rat liver sections as a substrate. Afterwards, arthritis sera were further studied in cultures of human skin fibroblasts and the HEp-2 cell line, with or without colchicine treatment.

Results using liver as substrate showed that 31% of the arthritic rats showed a cytoskeleton staining pattern throughout the cytoplasm, with higher intensity of staining along the surface membranes, particularly in pericanalicular regions. This staining was suggestive of intermediate filament autoantibodies. When sera were analyzed on cultured cells, the results showed that the pattern is identical to the arrangement described for intermediate filaments and different from those seen with antiactin antibodies. Colchicine pretreatments ruled out antitubulin activity. Further analysis by immunoblotting revealed that autoantibodies did not recognize intermediate filament proteins when these were denatured in the electrophoretic process.

The development of autoantibodies to intermediate filament proteins, both cytokeratin and vimentin, has been demonstrated in sera from rats with AA, in a similar manner to that described in human RA.