CONTINUING EDUCATION :: AUTOIMMUNE
Regardless of the detection method, DFS ANA and/or anti-DFS70 antibodies have been detected at elevated frequency in apparently healthy individuals (0–21.6 percent), but also in routine ANA screening cohorts (0.3–16.6 percent), and various non-SARD inflammatory and neoplastic conditions (3.3–71.4 percent; for example, Vogt-Harada syndrome, atopic dermatitis, psoriasis, interstitial cystitis, Hashi- moto’s thyroiditis, ocular diseases, chronic fatigue syndrome, asthma, or prostate cancer. In con- trast, they are rare in patients with SARD (0–28.6 percent), showing an overall frequency of only 2.8–4.5 percent, which is remarkably lower than in healthy individuals and control cohorts. Anti- DFS70 reactivity in SARD is usually accompanied by additional SARD-related antibodies, while iso- lated anti-DFS70 reactivity in SARD reportedly amounts to only 0.5–0.7 percent.5,6 Thus, antibodies to DFS70 are increas- ingly regarded as a potential negative predictive biomarker for excluding the diagnosis of SARD, particularly in the absence of clinically relevant ANA. This is supported by studies reporting on healthy individuals with isolated anti- DFS70 reactivity who did not develop SARD within a follow-up of three to four years (“benign autoimmunity”), and by a likelihood ratio (LR+) for the absence of SARD of 10.9 ascribed to isolated reactivity to DFS70.7 Overall, a few recent surveys have examined the prevalence of DFS ANA in sera submitted for routine ANA screen- ing, but only some of these used anti- DFS70 assays to confirm the antibod- ies’ specificity in all or in just a subset of tested samples. Considering also the diverse composition of the screened cohorts as well as the differences in assays and IFA interpretation, the cur- rently available data still requires more research. But there is strong evidence that isolated anti-DFS70 positivity— in the absence of disease-associated ANA—indeed correlates negatively with a SARD diagnosis. Anti-DFS70 testing can already help prevent unnecessary referrals to tertiary care specialists and potentially unneces- sary (toxic) treatment. Also, there are economic implications for the healthcare system. In a Spanish cohort of 181 patients a proposed algorithm that included anti-DFS70 testing saved approximately $70k of combined lab costs and out- patient clinic visits across all patients.8
From a U.S.
perspective, this might be an underestimation as the healthcare expenditures are significantly greater in the U.S. as compared to Spain or Europe, in general.
A practical community hospital experience report In order to illustrate the practical impact of anti- DFS70 testing, John B. Carter, MD and Sara Carter, MT(ASCP)SM,SI from Lexington Medical Center Laboratory (LMC) in West Columbia, SC discuss below their experience in a community hospital setting. LMC is one of the first testing facilities in the U.S. to adopt use of the ICAP system.
Developing an understanding for anti-DFS70 For many years the laboratory noted frequent, often high-titer (>10,240) speckled ANAs having a negative 6-test anti-Extractable Nuclear Antigens (anti-ENA)/anti-DNA profile and no clinical features of autoimmune rheumatic disease. When a mitotic-rich HEp-2 cell substrate became available, the laboratory noted many of these speckled ANAs to have strong fluorescence of mitotic figures (metaphase plates).
Figure 1. AC-2: Anti-DFS70 pattern on HEp-2 cells, courtesy of LMC, West Columbia, SC.
Thus, the team termed these a “Mixed Speckled/ Homogeneous (MS/H) ANA of uncertain signifi- cance,” a pattern that now is identified as a “Dense Fine Speckled (DFS),” with ICAP designation, “AC-2.”
Recent technical advances enabled the com- munity hospital immunology lab to significantly upgrade testing services. In an ongoing study of over 13,000 cases of routine DFS70 ANA testing it was noted that DFS, AC-2 was a common ANA pattern (21 percent of positive ANAs) that was read- ily apparent by IFA on a high-mitotic substrate,
MLO-ONLINE.COM JULY 2019 9
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72
