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VIPase autoantibodies in Fas ‐defective mice and patients with autoimmune disease
Author(s) -
Bangale Yogesh,
Karle Sangeeta,
Planque Stephanie,
Zhou YongXin,
Taguchi Hiroaki,
Nishiyama Yasuhiro,
Li Lan,
Kalaga Ravishankar,
Paul Sudhir
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0475com
Subject(s) - vasoactive intestinal peptide , autoantibody , serine protease , chemistry , protease , autoimmune disease , systemic lupus erythematosus , neurotensin , enzyme , autoimmune thyroiditis , microbiology and biotechnology , biochemistry , immunology , antibody , biology , thyroiditis , endocrinology , medicine , neuropeptide , receptor , disease , thyroid
The immunoregulatory neuropeptide vasoactive intestinal peptide (VIP) was cleaved by purified IgG from Fas ‐defective C3H/ gld mice, lupus patients, and autoimmune thyroiditis patients. No VIPase activity was detected in IgG from control mice and humans. Kinetic analyses of VIPase IgG preparations suggested low‐affinity recognition of VIP. Yet the VIPase activity was VIP selective, judged by lack of correlation with other protease activities expressed by the IgG and by noninterference of unrelated peptides in the activity. Recombinant Fv constructs selected from a human lupus phage show library displayed VIPase activity, confirming that the active site is located in the V domains. Inhibition of the VIPase activity by di‐isopropylfluorophosphate suggested a serine protease‐like mechanism of catalysis. Irreversible binding of a biotinyated phosphonate diester by the IgG and Fv preparations was observed, consistent with the presence of activated nucleophiles similar to those in enzymes capable of covalent catalysis. These observations show that VIP is a target for specific catalytic autoantibodies in autoimmune disease.