ANA Patterns

AC-2 - Nuclear dense fine speckled


Previous Nomenclature	None
Description	Speckled pattern distributed throughout the interphase nucleus with characteristic heterogeneity in the size, brightness and distribution of the speckles. Throughout the interphase nucleus, there are some denser and looser areas of speckles (very characteristic feature). The metaphase plate depicts strong speckled pattern with some coarse speckles standing out.
Antigen Association	DFS70/LEDGF

Clinical Relevance
First level information
About Clinical Relevance & List of Abbreviations

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Commonly found as high titer HEp-2 IIFA-positive in apparently healthy individuals or in patients who do not have a systemic autoimmune rheumatic disease (SARD) (9)

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The negative association with SARD is only valid if the autoreactivity is confirmed as being directed to DFS70 (also known as LEDGF/p75) and if no other common ENA is recognized (20, 21)

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Both in apparently healthy individuals as well as patients who do not have a SARD the AC-2 pattern may be caused by autoantibodies to other antigens than DFS70 (22)

Note: Confirmatory assays for anti-DFS70 antibodies may be available only in specialty clinical laboratories.

First level information references

Mariz HA, Sato EI, Barbosa SH, et al. Pattern on the antinuclear antibody-HEp-2 test is a critical parameter for discriminating antinuclear antibody-positive healthy individuals and patients with autoimmune rheumatic diseases. Arthritis & Rheumatism 2011;63:191-200.

20.

Watanabe A, Kodera M, Sugiura K, et al. Anti-DFS70 antibodies in 597 healthy hospital workers. Arthritis Rheum 2004;50:892-900.

21.

Mahler M, Parker T, Peebles CL, et al. Anti-DFS70/LEDGF antibodies are more prevalent in healthy individuals compared to patients with systemic autoimmune rheumatic diseases. J Rheumatol 2012;39:2104-10.

22.

Ochs RL, Mahler M, Basu A, et al. The significance of autoantibodies to DFS70/LEDGFp75 in health and disease: integrating basic science with clinical understanding. Clin Exp Med 2016;16:273-93.

Second level information

None

Second level information references

None

FAQ

The pseudo-DFS pattern? Some samples yield a nuclear speckled pattern with similar staining at the mitotic chromatin (metaphase and anaphase), very similar to AC-2 (nuclear dense fine speckled pattern), but do not yield a positive result in immunoassays specific for anti-DFS70 antibodies. How should I report such pattern since it is not exactly the AC-2 pattern and there is no anti-DFS70 reactivity? Is this pattern defined by ICAP?

This is an interesting question and reflects a challenge frequently encountered by ANA laboratories. At the present time, the â€œpseudo-DFSâ€ nomenclature has not been endorsed by ICAP or included in the ICAP algorithm. Nevertheless, there is published evidence that not all sera having a nuclear â€œdenseâ€ fine speckled pattern with similarly stained mitotic chromatin contain detectable anti-DFS70 autoantibodies. This situation may reflect a HEp-2 IFA pattern that is distinct from the anti-DFS70 positive AC-2 pattern even though it stains the interphase nuclei and mitotic chromatin with a speckled texture. However, the speckled texture is slightly different from the genuine AC-2 pattern (1, 2). The anti-DFS70-positive AC-2 pattern has a speckled texture that is heterogeneous within each nucleus, with some denser speckled areas adjacent to sparser areas; and areas with larger and brighter speckles intercalated with areas with smaller and dimer speckles. The same applies to the staining of mitotic chromatin. Some investigators have suggested the term â€œpseudo-DFSâ€ to designate sera that do not have these precise AC-2 staining characteristics (1, 2), The Autoantibody Standardizing Committee offers free of charge reference sera with several HEp-2 IFA patterns and antibody specificities (http://www.autoab.org/), including a reference material for AC-2 pattern (with reactivity to DFS70) (3). This can help in the exact recognition of the AC-2 pattern. Note that the specific autoantibody target(s) and the clinical relevance for the pseudo-DFS pattern but anti-DFS70 negative remains to be published.

1. Mahler M, Andrade LE, Casiano CA, Malyavantham K, Fritzler MJ. Anti-DFS70 antibodies: an update on our current understanding and their clinical usefulness. Expert Rev Clin Immunol. 2019;15:241-250.
2. Infantino M, Bizzaro N, Grossi V, Manfredi M. The long-awaited 'pseudo-DFS pattern'. Expert Rev Clin Immunol. 2019 15(5):445.
3. Dellavance A, Baldo DC, Zheng B, Mora RA, Fritzler MJ, Hiepe F, Ronnelid J, Satoh M, Garcia-De La Torre I, Wener MH, Chan EKL, Andrade LEC. Establishment of an international autoantibody reference standard for human anti-DFS70 antibodies: proof-of-concept study for a novel Megapool strategy by pooling individual specific sera. Clin Chem Lab Med. 2019;57:1754-63.
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Date: November 26, 2019