title: VIPase autoantibodies in Fas-defective mice and patients with autoimmune disease.
abstract: 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.
authors.affiliation: Chemical Immunology Research Center, Department of Pathology, University of Texas Medical School, 6431 Fannin, Houston, TX 77030, USA.
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Bangale
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Karle
authors.forename: Stephanie
authors.initials: S
authors.lastname: Planque
authors.forename: Yong-Xin
authors.initials: YX
authors.lastname: Zhou
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Taguchi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nishiyama
authors.forename: Lan
authors.initials: L
authors.lastname: Li
authors.forename: Ravishankar
authors.initials: R
authors.lastname: Kalaga
authors.forename: Sudhir
authors.initials: S
authors.lastname: Paul
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000235:genetics / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism*; D002384:Catalysis; D003001:Cloning, Molecular; D006801:Humans; D006868:Hydrolysis; D007128:Immunoglobulin Fragments / Q000235:genetics / Q000378:metabolism; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009154:Mutation; D009842:Oligopeptides / Q000378:metabolism; D013954:Thyroglobulin / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000276:immunology / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*; D019014:fas Receptor / Q000235:genetics
chemical_list: D001323:Autoantibodies; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D009842:Oligopeptides; D019014:fas Receptor; C055966:immunoglobulin Fv; D014660:Vasoactive Intestinal Peptide; C025273:prolyl-phenylalanyl-arginine-4-methylcoumaryl-7-amide; D013954:Thyroglobulin