Autoantibodies to a transfer RNA-associated protein in a murine model of chronic graft versus host disease
| Autor: | Gelpí, C., Martinez, M. A., Silvia Vidal, Targoff, I. N., Rodriguez-Sanchez, J. L. |
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| Rok vydání: | 1994 |
| Předmět: | |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.152.4.1989 |
| Popis: | We established chronic graft vs host disease (GVHD) in (C57BL/10 x DBA/2)F1 mice with an injection of lymphoid cells from the parental DBA/2 strain. In addition to Abs earlier reported, of the 20 animals studied 13 developed Abs against transfer RNA/protein particles. Ten of the 13 sera immunoprecipitated a similar-sized RNA that co-migrated in PAGE with isoleucine tRNA. In immunoblots against proteins affinity purified using anti-isoleucyl-tRNA synthetase prototype serum, 7 of the 10 sera reacted with a polypeptide of 76 kDa that was similar in size to a protein recognized by a human anti-isoleucyl-tRNA synthetase serum. Three of 10 sera significantly and specifically inhibited isoleucyl-tRNA synthetase enzyme activity and one inhibited lysyl-tRNA synthetase activity. These data suggest that the autoantibodies to tRNA-associated proteins that develop in GVHD mice may react with amino acyl-tRNA synthetases, particularly those belonging to the multienzyme complex. Such autoantibodies are associated with myositis in humans, and these mice showed evidence compatible with myositis that appeared to be a manifestation of their GVHD. No previous example of spontaneous development of antisynthetases in animals has been described. We also demonstrated the presence of Abs against the NOR:90 nucleolar Ag as a new target in chronic GVHD. We conclude that chronic GVHD in mice provides a model for the study of the autoimmune responses that characterize human diseases such as mixed connective tissue disease, scleroderma, SLE, and myositis with a wider autoantibody response than that described so far. |
| Databáze: | OpenAIRE |
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