Redefining the Scl-70 indirect immunofluorescence pattern: autoantibodies to DNA topoisomerase I yield a specific compound immunofluorescence pattern

• Published in: Rheumatology (Oxford, England) Vol. 48; no. 6; pp. 632 - 637
• Main Authors: Dellavance, Alessandra, Gallindo, Cristiane, Soares, Mariana Guanaes, da Silva, Neusa Pereira, Mortara, Renato Arruda, Andrade, Luís Eduardo Coelho
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.06.2009; Oxford Publishing Limited (England)
• Subjects: Anti-nuclear antibodies; Autoantibodies; Autoantibodies - immunology; Autoantigens - blood; Basic Science; Biological and medical sciences; Cell Line; Cell Nucleolus - chemistry; Cell Nucleus - chemistry; Chromosomes - chemistry; Cytoplasm - chemistry; Diseases of the osteoarticular system; DNA topoisomerase I; DNA Topoisomerases, Type I - immunology; Fluorescent Antibody Technique, Indirect; Humans; Interphase; Medical sciences; Mitosis; Nuclear Proteins - blood; Nucleolus Organizer Region - chemistry; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Scl-70; Scleroderma, Systemic - immunology; Systemic sclerosis; Anti-nuclear antibodies; Autoantibodies; Scl-70; Systemic sclerosis; DNA topoisomerase I; Autoimmunity; Immunopathology; Connective tissue disease; Skin disease; Enzyme; Antibody; DNA topoisomerase; Rheumatology; Autoantibody; Autoimmune disease; Indirect immunofluorescence; Isomerases; Systemic disease; Scleroderma
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/kep070

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.