title: Autoantibodies to the epidermal growth factor receptor in systemic sclerosis, lupus, and autoimmune mice.
abstract: Autoantibodies to the recombinant extracellular domain of epidermal growth factor receptor (exEGFR) were detected by ELISA in the serum of Fas-defective old MRL/MpJ/lpr and C3H/HeJ/gld mice, but not young mice from these strains, or nonautoimmune young and old BALB/c, MRL/MpJ/++, and C3H/HeJ/MMTV mice. Compared with control human subjects without autoimmune disease, the frequency of exEGFR-binding autoantibodies was increased in scleroderma (systemic sclerosis) patients and to a lesser extent in lupus patients. Phage autoantibodies (Fv fragments) isolated from a lupus library by selection on a linear epitope of EGFR (residues 294-310) displayed the ability to bind exEGFR. Treatment of EGFR-expressing A431 cells with autoantibodies purified by affinity chromatography on immobilized exEGFR resulted in specific staining of the cells. Short-lived but strong inhibition of cellular DNA synthesis was observed in the presence of the autoantibodies. We concluded that autoantibody responses to EGFR hold the potential of fulfilling a pathogenic role in autoimmune disease.
authors.affiliation: Chemical Immunology and Therapeutics Research Center, Department of Pathology and Internal Medicine, University of Texas-Houston Medical School, Houston, Texas 77030, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Planque
authors.forename: Yong-Xin
authors.initials: YX
authors.lastname: Zhou
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nishiyama
authors.forename: Meenal
authors.initials: M
authors.lastname: Sinha
authors.forename: Maureen
authors.initials: M
authors.lastname: O'Connor-Mccourt
authors.forename: Frank C
authors.initials: FC
authors.lastname: Arnett
authors.forename: Sudhir
authors.initials: S
authors.lastname: Paul
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000276:immunology*; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D066246:ErbB Receptors / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D008177:Lupus Vulgaris / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011485:Protein Binding; D012595:Scleroderma, Systemic / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D001323:Autoantibodies; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; C055966:immunoglobulin Fv; D004247:DNA; D066246:ErbB Receptors