Autoantibody response against a novel testicular antigen protein highly expressed in testis (PHET) in SSc patients.
Systemic sclerosis (SSc) is characterized by excessive fibrosis and autoantibody production. However, the pathogenesis of SSc is still under investigation. We have demonstrated that a novel testicular antigen, protein highly expressed in testis (PHET), is overexpressed in SSc dermal fibroblasts and targeted by autoantibodies. PHET was identified by screening of HepG2 cDNA library using an SSc serum and was found to belong to UniGene cluster of sperm associated antigen 9 (SPAG9) from its nucleotide sequence. PHET mRNA expression was examined by RT-PCR using mRNA panels of human tissues, and PHET mRNA was highly expressed only in testis in normal tissues. Anti-PHET antibodies were detected in 8.4% of sera of SSc patients by immunoblotting, and associated with diffuse scleroderma and lung involvement. Expression of PHET mRNA and protein was increased in cultured SSc dermal fibroblasts compared with control fibroblasts. These results suggest that ectopic expression of PHET in dermal fibroblasts induces autoantibody production against PHET in patients with SSc.
Yasuoka
Hidekata
H
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, 3459 Fifth Avenue NW628 MUH, Pittsburgh, PA 15213, USA. yasuokah@upmc.edu
Kuwana
Masataka
M
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology* / Q000378:metabolism; D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood; D001324:Autoantigens / Q000276:immunology*; D018076:DNA, Complementary; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015723:Gene Library; D006801:Humans; D008297:Male; D012595:Scleroderma, Systemic / Q000276:immunology* / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000378:metabolism; D013737:Testis / Q000276:immunology* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D001323:Autoantibodies; D001324:Autoantigens; D018076:DNA, Complementary; C111047:SPAG9 protein, human