Autoantibodies to the epidermal growth factor receptor in systemic sclerosis, lupus and atoimmune mice
Autor: | Yasuhiro Nishiyama, Maureen O'Connor-McCourt, Yong Xin Zhou, Sudhir Paul, Frank C. Arnett, Meenal Sinha, Stephanie Planque |
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Rok vydání: | 2003 |
Předmět: |
Biology
Biochemistry Scleroderma Autoimmune Diseases law.invention Mice law Tumor Cells Cultured Genetics medicine Animals Humans pharmaceutical Epidermal growth factor receptor skin and connective tissue diseases Immunoglobulin Fragments Molecular Biology Autoantibodies Autoimmune disease Lupus Vulgaris Mice Inbred BALB C Mice Inbred C3H Scleroderma Systemic Systemic lupus erythematosus Linear epitope Autoantibody DNA medicine.disease ErbB Receptors Immunoglobulin G Immunology Recombinant DNA biology.protein A431 cells Protein Binding Biotechnology |
DOI: | 10.1096/fj.01-0847com |
Popis: | 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. |
Databáze: | OpenAIRE |
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