Identification of specific autoantigens in Sjögren's syndrome by SEREX.
We carried out SEREX (serological analysis of antigens by recombinant cDNA expression cloning) using sera from patients with Sjögren's syndrome (SjS) and investigated the frequencies of autoantibodies against autoantigens identified by SEREX in the sera of healthy individuals (HI) and patients with SjS, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). IFI16 and two kelch-like proteins, KLHL12 and KLHL7, were found to be novel autoantigens in SjS by SEREX. A markedly high frequency of anti-IFI16 autoantibodies was observed in the sera of SjS (SjS, 70%; RA, 13%; SLE, 33%; HI, 0%). Interestingly, all serum samples from SjS demonstrated immunoreactivity against one or both of IFI16 and SS-B/La. The presence of autoantibodies against KLHL12 and KLHL7 in the sera was significantly specific to SjS (23% and 17%, respectively), as they were not detected in RA, SLE or HI. Furthermore, we confirmed that transcripts of these autoantigens were expressed preferentially in the salivary glands and immuno-privileged testes. Our results suggest these autoantigens may be useful as serological markers for the clinical diagnosis of SjS and may play a crucial role as organ-specific autoantigens in the aetiopathogenesis of SjS. This study warranted clinical evaluations of autoantibodies against IFI16, KLHL12 and KLHL7 in combination with anti-SS-B/La autoantibodies.
Uchida
Kazuo
K
Second Department of Oral and Maxillofacial Surgery, Aichi Gakuin University School of Dentistry, Nagoya, Japan. noriuchi@dpc.aichi-gakuim.ac.jp
Akita
Yoichi
Y
Matsuo
Keitaro
K
Fujiwara
Shigeyoshi
S
Nakagawa
Atsuko
A
Kazaoka
Yoshiaki
Y
Hachiya
Hiroshi
H
Naganawa
Yoshiyuki
Y
Oh-Iwa
Ichiro
I
Ohura
Kiyoshi
K
Saga
Shinsuke
S
Kawai
Tatsushi
T
Matsumoto
Yoshinari
Y
Shimozato
Kazuo
K
Kozaki
Ken-Ichi
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000276:immunology*; D015152:Blotting, Northern; D015153:Blotting, Western; D005260:Female; D015723:Gene Library; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism; D009687:Nuclear Proteins / Q000276:immunology / Q000378:metabolism; D010750:Phosphoproteins / Q000276:immunology / Q000378:metabolism; D012469:Salivary Glands / Q000276:immunology; D012859:Sjogren's Syndrome / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; C485646:KLHL2 protein, human; C505353:KLHL7 protein, human; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C076700:IFI16 protein, human