Autoantibodies to a transfer RNA-associated protein in a murine model of chronic graft versus host disease.
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.
Gelpí
C
C
Department of Immunology, Hospital de Sant Pau, Universitat Autónoma de Barcelona, Spain.
Martinez
M A
MA
Vidal
S
S
Targoff
I N
IN
Rodriguez-Sanchez
J L
JL
D000818:Animals; D001323:Autoantibodies / Q000032:analysis*; D002466:Cell Nucleolus / Q000276:immunology; D002908:Chronic Disease; D005455:Fluorescent Antibody Technique; D006086:Graft vs Host Disease / Q000276:immunology*; D015151:Immunoblotting; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011233:Precipitin Tests; D012343:RNA, Transfer / Q000276:immunology*; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology*
D001323:Autoantibodies; D017411:Ribonucleoproteins, Small Nuclear; D012343:RNA, Transfer