Background: Autoantibodies to the 20S proteasome represent an unspecific but common serological phenomenon in patients with systemic autoimmune diseases. Interestingly, a high prevalence of these antibodies have been observed in patients with connective tissue diseases, where anti-nuclear antibodies (ANAs) serve as an important diagnostic screening test.
Objective: To disclose interference of anti-proteasome antibodies with known ANA patterns.
Methods: Anti-proteasome antibodies were isolated for comprehensive immunofluorescence analyses. The immunofluorescence pattern of human anti-proteasome antibodies was compared with a panel of monoclonal and polyclonal reference antibodies, and colocalisation was analysed using confocal microscopy.
Results: Anti-proteasome antibodies clearly contributed to the ANA patterns of their respective serum samples from patients with different rheumatic disorders. In addition to the nuclear pattern, proteasomal staining was also detectable in the cytoplasm, at the endoplasmic reticulum and perinuclear regions showing features overlapping with other known autoantibodies such as those to mitochondria. The specificity of anti-proteasome antibodies was proved by competition experiments and by colocalisation with monoclonal reference antibodies in confocal microscopy.
Conclusion: In ANA diagnostics, interference of anti-proteasome antibodies will have to be taken into account, especially in the differentiation of anti-cytoplasmatic autoantibodies.
- ANA, anti-nuclear antibody
- FITC, fluorescein isothiocyanate
- IIF, indirect immunofluorescence
- PA28, proteasome activator
- PAGE, polyacrylamide gel electrophoresis
- TAP, transporter associated with antigen processing
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↵* These authors contributed equally to this work.
Published Online First 30 June 2006
Funding: This study was supported by the Kompetenznetz-Rheuma C2.3 of the German Ministry of Education and Science, and by grants from Deutsche Forschungsgemeinschaft (SFB421/B13 and DFG Ku1261).
Competing interests: None declared.