CONTINUING EDUCATION :: AUTOIMMUNE
Isolated anti-DFS70 autoantibodies: Negative disease correlation with a positive impact
By John B. Carter MD, Sara Carter MT(ASCP)SM,SI, and Oliver Sendscheid, PhD T
he presence of antinuclear autoantibodies (ANA) is one of the key diagnostic criteria of systemic autoimmune rheumatic diseases (SARD), such as systemic lupus erythematosus (SLE), Sjogren’s syndrome, systemic sclerosis, dermatomyositis/polymyositis (DM/PM), and mixed connective tissue diseases (MCTD). Indirect immunofluorescence assays (IFA) using human epithelial (HEp-2) cells are the American College of Rheumatologists recommended “gold standard” for ANA screening as this substrate provides a variety of more than 100 native autoantigens including proteins, DNA, and ribonucleoproteins.1
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Upon completion of this article, the reader will be able to:
1. Discuss the utility of ANA autoantibody testing in relation to SARD diseases.
2. Recall the pattern and antibody specificity for confirmatory testing and describe its utility.
3. Recall the committee for the standardization and diagnostic use of the DFS ANA pattern.
4. Discuss the findings that an outside laboratory found when it adopted the use of confirmatory testing when finding DFS patterns on ANA tests.
8 JULY 2019
MLO-ONLINE.COM Relevance of anti-DFS70 testing
The dense fine speckled (DFS) nuclear pattern is one of the most common IFA patterns encountered in the ANA screening routine of clinical diagnostic laboratories, often occurring in very high titers. The autoantibodies producing this pattern target the DFS protein of 70 kDa (DFS70), which is iden- tical to the Lens Epithelium-Derived Growth Fac- tor or transcription co-activator p75 (LEDGFp75). DFS70/LEDGFp75 confers cell protection by regu- lating transcription of stress-related genes and is relevant to the pathophysiology of AIDS, cancer, autoimmunity, and inflammatory conditions. Anti-DFS70 autoantibodies might play protective, pathogenic, or sensor roles.2
The International Consensus on ANA Patterns (ICAP) committee has classified the DFS pattern as “AC-2,” a competency level recognition pat- tern, defined by a dense and heterogeneous speck- led staining in the nucleoplasm of interphase cells (sparing the nucleoli) and the metaphase chromosomal plate.3
(Figure 1)
Recognition of this pattern on HEp-2 substrates is challenging as it can be confused with other nuclear patterns or may occur in the context of another clinically relevant ANA, and because IFA interpretation is dependent on technician expertise.
Thus, a positive DFS IFA result has to be fol- lowed by a monospecific immunoassay (e.g., ELISA, ChLIA, immunoblot) to accurately confirm the presence of anti-DFS70 autoantibodies, as recommended in diagnostic algorithms.4
The
clinical significance of anti-DFS70 autoantibodies is not clear as there is no known disease specificity for this autoantibody.2
Dense fine speckled (DFS, AC-2) indirect immunofluorescence staining on HEp2 cells. Image courtesy of EUROIMMUN.
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