Identification of AHNAK as a novel autoantigen in systemic lupus erythematosus.
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.
Sköldberg
Filip
F
Department of Medical Sciences, Uppsala University, University Hospital, 751 85 Uppsala, Sweden. Filip.Skoldberg@medsci.uu.se
Rönnblom
Lars
L
Thornemo
Maria
M
Lindahl
Anders
A
Bird
Phillip I
PI
Rorsman
Fredrik
F
Kämpe
Olle
O
Landgren
Eva
E
D000595:Amino Acid Sequence; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D053804:Granzymes; D006801:Humans; D015151:Immunoblotting; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011233:Precipitin Tests; D014176:Protein Biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D014407:Tumor Cells, Cultured
C075176:AHNAK protein, human; C489573:Ahnak protein, rat; D001323:Autoantibodies; D001324:Autoantigens; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; C509213:GZMB protein, human; D053804:Granzymes; C509215:Gzmb protein, rat; D012697:Serine Endopeptidases; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases