EUROPattern Suite technology for computer-aided immunofluorescence microscopy in autoantibody diagnostics

Abstract

Antinuclear autoantibodies (ANA) are highly informative biomarkers in autoimmune diagnostics. The increasing demand for effective test systems, however, has led to the development of a confusingly large variety of different platforms. One of them, the indirect immunofluorescence (IIF), is regarded as the common gold standard for ANA screening, as described in a position statement by the American College of Rheumatology in 2009. Technological solutions have been developed aimed at standardization and automation of IIF to overcome methodological limitations and subjective bias in IIF interpretation. In this review, we present the EUROPattern Suite, a system for computer-aided immunofluorescence microscopy (CAIFM) including automated acquisition of digital images and evaluation of IIF results. The system was originally designed for ANA diagnostics on human epithelial cells, but its applications have been extended with the latest system update version 1.5 to the analysis of antineutrophil cytoplasmic antibodies (ANCA) and anti-dsDNA antibodies.

Automated antinuclear immunofluorescence antibody analysis is a reliable approach in routine clinical laboratories

“…To our knowledge, most literatures focused on reporting positive or negative rate on single devices [11,12,[26][27][28], even less data attempted to compare patterns between different assay kits [9,29]. Therefore, we further evaluated the discrepancy caused by the HEp-2 assay kits in our clinical laboratory.…”

“…Recently, many studies focused on the comparisons between automatic and manual microscope reading or discrepancies between various computer-aided ANA pattern diagnostic systems [11][12][13][14][15][16]. However, few studies evaluated the reliability of the autotiter evaluation system [17].…”

Multiparametric autoimmune diagnostics: recent advances

“…More recently, pattern recognition devices have become available that enable automated reading of these multiparametric IIF assays. 8,9,11 If fully automated, medium-to-high volume testing can be handled. In case of the CytoBead method, the ANCA specificity assays even generate quantitative results by utilizing a standard curve based on reference sera of the International Center for Disease Control and Prevention (CDC).…”

“…6 Although, because of improvement of the antigen-specific assays, the necessity of IIF screening is being disputed, 13 multiparametric IIF very elegantly combines the cellular-and antigen-specific substrates and thereby follows the international consensus. 9,11,14 The improvements achieved in the detection of MPO-and PR3-ANCA are primarily based on the methodology used for coating the antigen to the solid phase. Binding of the antigen via a capturing monoclonal antibody, ie, second-generation immunoassay, or via a peptide-linker, ie, third-generation immunoassay, has been proven superior to direct coating of the antigen, ie, first-generation immunoassay.…”

ANA IIF Automation: Moving towards Harmonization? Results of a Multicenter Study

“…As an attempt to overcome this lack of standardization, manufacturers have developed several computer-aided diagnosis (CAD) systems, which acquire, analyze, and display digital images of stained IIF slides [9, 10]. Currently available automated ANA IIF image analyzing systems (NOVA View (Inova Diagnostics, San Diego, USA), AKLIDES® (Medipan, Berlin, Germany), Zenit G-Sight (Menarini, Florence, Italy), EUROPattern (Euroimmun, Lübeck, Germany), Image Navigator® (Immuno Concepts, Sacramento, USA), and HELIOS® (Aesku, Wendelsheim, Germany)) have already been reviewed extensively [9, 10].…”