Rheumatology Advance Access originally published online on April 24, 2009
Rheumatology 2009 48(6):632-637; doi:10.1093/rheumatology/kep070
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Redefining the Scl-70 indirect immunofluorescence pattern: autoantibodies to DNA topoisomerase I yield a specific compound immunofluorescence pattern
1Fleury Medicine and Health, 2Rheumatology Division and 3Microbiology, Immunology and Parasitology Division, Universidade Federal de São Paulo, São Paulo, Brazil.
Correspondence to: Luís Eduardo Coelho Andrade, Rheumatology Division, Universidade Federal de São Paulo, Rua Botucatu 740 3° andar, 04023-062 São Paulo, Brazil. E-mail: luis.andrade{at}unifesp.br
| Abstract |
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Objectives. To report on a novel IIF pattern specifically associated with antibodies to DNA topo I.
Methods. A novel compound IF pattern, designated Scl-70 pattern, was characterized in routine ANA-HEp-2 IIF screening. Within the last 3 years, all serum samples presenting the Scl-70 pattern at the ANA-HEp2 IIF screening were tested for anti-topo I reactivity. Conversely, 16 serum samples with known anti-topo I reactivity and affinity-purified anti-topo I antibody preparations were tested for the Scl-70 pattern.
Results. The Scl-70 pattern comprised the staining of five cellular regions: nucleus, nucleolus and cytoplasm in interphase cells; nucleolar organizing region (NOR) and chromosomes in mitotic cells. All 81 serum samples selected as Scl-70 pattern reacted with topo I. All 16 anti-topo I samples and antibody preparations reproduced the Scl-70 pattern. This compound IF pattern was consistently observed in different commercial HEp-2 cell slides and in home-made slides with HEp-2 cells and human fibroblasts fixed with alternative protocols. Double IIF experiments demonstrated the co-localization of topo I and human upstream binding factor at the NOR.
Conclusions. The Scl-70 pattern belongs to the group of compound IF patterns that hold strong association with the respective autoantibody specificities, such as that observed with centromere protein F (CENP-F) and nuclear mitotic apparatus-1 (NuMA-1) protein. The identification of the Scl-70 pattern at routine ANA-HEp-2 IIF screening may lead to implementation of specific tests for the identification of anti-topo I antibodies. In addition, the Scl-70 pattern outlines cellular domains other than those previously reported for topo I, which is of interest for further understanding the roles of this enzyme in cell biology.
KEY WORDS: Anti-nuclear antibodies, DNA topoisomerase I, Scl-70, Autoantibodies, Systemic sclerosis
Submitted 6 December 2008;
revised version accepted 6 March 2009.
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