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| Previous Nomenclature | Scl-70-like, Scl-86, DNA Topo I |
| Description |
The Topoisomerase I-like pattern is associated with staining of five subcellular regions [1, 2]:
1) Prominent fine nuclear speckled (AC-4 type) staining in interphase cells.
2) Consistent strong fine speckled staining of condensed chromatin in mitotic cells. Depending on the serum dilution, mitotic chromatin staining may appear homogeneous. 3) Strong staining of nucleolar organizing region (NOR) associated with chromosomes in mitotic cells. This NOR staining may be obscured by bright chromosomal staining as NORs are not always on the same focal plane (see figure below). 4) Weak cytoplasmic staining in interphase and mitotic cells depicts a delicate network radiating from the perinuclear area towards the plasma membrane; in general, after dilution of sera to end-point titers more prominent cytoplasmic staining can be observed. 5) Variable nucleolar staining can appear as a punctate or perinucleolar staining in interphase cells. This nucleolar staining is not a universal feature of this pattern. This 5-element compound staining pattern has been observed in most commercial HEp-2 cell slides, but there may be some variations in the expression of each element depending on the slide manufacturer. The detection of all 5 elements may be a challenge especially when only a single serum dilution is used (e.g. strong mitotic chromatin staining obscures NOR) or in many semi-automated systems when images are often imaged on a single focal plane (e.g. NOR or cytoplasmic staining is not in same focal plane as interphase nuclei). Practical recommendation if the features 1 and 2 (above) are observed suggestive of AC-29, the next step should be to look for feature 3 (positive NOR staining) by focusing at different focal planes for NORs on mitotic chromatin. Next, the presence of feature 4 (cytoplasmic staining) and feature 5 (nucleolar staining) should be evaluated. 
INOVA HEp-2 images illustrating the AC-29 pattern with staining in all 5 compartments. Panel A is a merged image from the other 3 panels (A', A'', A''') representing different optical sections/focal planes, each illustrating the unique stained structures not obvious in the other focal planes. In addition to the obvious nucleoplasmic and mitotic condensed chromatin staining, panel A' illustrates two bright NORs in focus (arrow) on condensed chromatin in the mitotic cell; panel A'' shows another NOR in focus (arrow) in the same cell; A''' shows characteristic cytoplasmic (arrowhead) and weak perinucleolar staining (short arrow) |
| Antigen Association | DNA topoisomerase I (formerly Scl-70) |
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Clinical Relevance
First level information About Clinical Relevance & List of Abbreviations |
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▶ The AC-29 pattern is highly specific for systemic sclerosis (SSc), in particular with diffuse cutaneous SSc and more aggressive forms of SSc [1-3]. ▶ If SSc is clinically suspected, it is recommended to perform a follow-up test for anti-Topoisomerase I; these antibodies are included in the classification criteria for SSc and the antigen is included in routine ENA profiles [3-5]. |
| First level information references |
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| Second level information |
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None |
| Second level information references |
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1. Andrade LEC, Klotz W, Herold M, Conrad K, Ronnelid J, Fritzler MJ, von Muhlen CA, Satoh M, et al. International consensus on antinuclear antibody patterns: definition of the AC-29 pattern associated with antibodies to DNA topoisomerase I. Clin Chem Lab Med. 2018;56:1783-8. 2. Dellavance A, Gallindo C, Soares MG, da Silva NP, Mortara RA, Andrade LE. Redefining the Scl-70 indirect immunofluorescence pattern: autoantibodies to DNA topoisomerase I yield a specific compound immunofluorescence pattern. Rheumatology (Oxford). 2009;48:632-7. 3. Johnson SR, Fransen J, Khanna D, Baron M, van den Hoogen F, Medsger TA, Jr., Peschken CA, Carreira PE, et al. Validation of potential classification criteria for systemic sclerosis. Arthritis Care Res. 2012;64:358-67. 4. van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, Matucci-Cerinic M, Naden RP, et al. 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis. 2013;72:1747-55. 5. Basu D, Reveille JD. Anti-scl-70. Autoimmunity. 2005;38:65-72. |
| FAQ |
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Fine Art with AC-29. Is it critical that all five elements of the subcellular domains associated with the AC-29 pattern be evaluated in order to correctly classify an individual serum as AC-29? In other words, can it be classified as AC-29 with staining of only some of the five elements? |