The specificity of disease-associated anti-fibrillarin autoantibodies compared with that of HgCl2-induced autoantibodies.
Autoantibodies against nucleolar components are a common serological feature of patients suffering from scleroderma, a collagen vascular autoimmune disease. An important target of these autoantibodies is a protein with an apparent molecular weight of 36 kDa and a pI value of 8.5, located in the dense fibrillar component of the nucleolus and therefore termed fibrillarin. Animal models in which abundant anti-nucleolar antibodies appear spontaneously have not yet been described; however, high levels of anti-fibrillarin antibodies can be induced by treating susceptible strains of mice with sub-toxic amounts of mercuric chloride. In this study, we have analysed the specificity of anti-fibrillarin autoantibodies of human and murine origin. Our results suggest that both species have similar, if not identical conformational epitopes that are the target of anti-fibrillarin autoantibodies; these epitopes require the presence of a 30-kDa fragment of the fibrillarin molecule. Post-translational modifications such as the dimethylation of arginines in the N terminus of the protein are not essential for antibody recognition.
Lübben
B
B
Institut für Molekularbiologie und Tumorforschung, Phillipps-Universität Marburg, Germany.
Rottmann
N
N
Kubicka-Muranyi
M
M
Gleichmann
E
E
Lührmann
R
R
D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D002466:Cell Nucleolus / Q000276:immunology*; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008627:Mercuric Chloride / Q000494:pharmacology; D051379:Mice; D008970:Molecular Weight; D010446:Peptide Fragments / Q000737:chemistry; D017434:Protein Structure, Tertiary
D001323:Autoantibodies; D002868:Chromosomal Proteins, Non-Histone; D000939:Epitopes; D010446:Peptide Fragments; C047458:fibrillarin; D008627:Mercuric Chloride