Laboratory screening of connective tissue diseases by a new automated ENA screening assay (EliA Symphony) in clinically defined patients
Introduction
The measurement of antinuclear antibodies (ANA) is used in the autoimmune laboratory for the screening of connective tissue diseases (CTD). ANA measurement are performed by indirect immunofluorescence (IIF) assay on cultured human epidermoid carcinoma cells (HEp-2 cells) [1]. However ANA-IIF is a time consuming procedure, difficult to automatize and standardize, and with poor reproducibility due to the subjective interpretation of results. After ANA-IIF positive results are subjected to ENA screening by enzyme immunoassay (EIA).
In the last few years, EIA kits have been developed for ANA and ENA screening, with the objective of replacing ANA-IIF and ENA screening by ANA–EIA. Commercially available kits for ANA determination use HEp-2 nuclear extracts, HEp-2 nuclear extracts plus purified or recombinant antigens, or purified and/or recombinant antigens. Comparison studies between ANA–IIF and ANA–EIA have been performed with discordant results [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], in part due to the antigenic composition of EIA screening reagents.
The objective of the present study was to evaluate an automated detection system for ENA screening which lacks anti-dsDNA for detection of connective tissue diseases (CTD) and to compare it with the classical HEp-2 cell ANA.
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Samples
A total of 170 serum samples were included in the study. The diagnosis of the patients was: CTD (n = 54), other autoimmune diseases (other-AD) (n = 26) and non-autoimmune diseases (non-AD) (n = 90). All patients came from specialized centers and were characterized with respect to gender, age, diagnosis and treatment. So, the study design did not reflect the routine situation; instead, groups were constructed artificially from well-defined, pre-characterized patients. The CTD group consisted of
Results
A summary of the results obtained is shown in Table 1. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), efficiency and positive and negative likelihood ratios are shown in Table 2. A sensitivity of 69% (95% CI: 56–81%) was obtained for HEp-2 IIF, and a slightly lower value of 63% (95% CI: 50–76%) for EliA™ Symphony. The combination of EliA™ Symphony and EliA™ dsDNA gave a sensitivity of 74% (95% CI: 62–85%). A specificity of 89% (95% CI: 84–95%) was
Discussion
In this study we compared the clinical diagnostic efficiency of ANA analyzed by IIF with that obtained with a new automated ENA screening enzyme immunoassay (EliA™ Symphony), which lacks anti-dsDNA in patients with CTD. In the predefined set of patients analyzed, the performance of the two techniques was very comparable. Efficiency was on the same level (∼ 82%) as were positive and negative likelihood ratios. Surprisingly, the combined use of EliA™ Symphony which lacks anti-dsDNA with EliA™
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2018, Seminars in Arthritis and RheumatismCitation Excerpt :The EliA Symphony with EliA dsDNA, composed of only 8 antigens was used as the SEIA in the study. Although the sensitivity of SEIA was marginally better than that of a previously mentioned study of Baronaite et al. [11], using the EliA Symphony with 7 antigens, the value obtained by Gonzalez et al. [19] was substantially reduced. For IIF, the applied cutoff of 1:160 might be the cause of the low sensitivity observed in the study [19], when compared to the values of other studies using the same kits (Supplementary Table S2) [12,14,22,39,40].
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