Identification of AHNAK as a novel autoantigen in systemic lupus erythematosus |
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Authors: | Sköldberg Filip Rönnblom Lars Thornemo Maria Lindahl Anders Bird Phillip I Rorsman Fredrik Kämpe Olle Landgren Eva |
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Institution: | Department of Medical Sciences, Uppsala University, University Hospital, 751 85 Uppsala, Sweden. Filip.Skoldberg@medsci.uu.se |
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Abstract: | To identify candidate autoantigens associated with arthritis, a rat chondrocyte cDNA library was immunoscreened with serum from a patient with rheumatoid arthritis. One isolated cDNA encoded part of AHNAK, a 700-kDa phosphoprotein with DNA binding properties, that appears to be involved in several signal transduction pathways. Immunoreactivity against an in vitro translated human AHNAK fragment was detected in 4.6% (5/109) of patients with rheumatoid arthritis, 29.5% (18/61) of patients with systemic lupus erythematosus (SLE), and 1.2% (2/172) of blood donors. Anti-AHNAK antibodies reacted with a recombinant human AHNAK fragment and with native AHNAK from C32 cell lysates. In vitro translated AHNAK fragment could be cleaved by granzyme B and caspase-3. Anti-AHNAK positive SLE patients had a higher frequency of homogeneous antinuclear antibody staining patterns and a lower frequency of recent mucosal ulcerations. This is the first report that AHNAK can be targeted by the immune system in autoimmune disease. |
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Keywords: | AHNAK systemic lupus erythematosus rheumatoid arthritis autoantibodies autoimmunity apoptosis granzyme B caspase-3 |
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