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. 2020 Jan 14;10:1385.
doi: 10.3389/fneur.2019.01385. eCollection 2019.

Autoantibody Diagnostics in Neuroimmunology: Experience From the 2018 Italian Neuroimmunology Association External Quality Assessment Program

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Free PMC article

Autoantibody Diagnostics in Neuroimmunology: Experience From the 2018 Italian Neuroimmunology Association External Quality Assessment Program

Matteo Gastaldi et al. Front Neurol. .
Free PMC article

Abstract

Background: Neuroimmunology has impressively expanded in the past decade. Novel assays, especially cell-based assays (CBAs) can detect conformational antibodies (Abs) recognizing antigens in their native conformation. Generally, the availability of in-house and of commercial tests has improved the diagnostics, but introduced demanding laboratory tasks. Hence, standardization and quality controls represent a key step to promote accuracy. We report on the results of the 2018 external quality assessment program (EQAP) organized by the Italian Neuroimmunology Association. Methods: EQAP regarded 10 schemes, including oligoclonal bands (OCBs), intracellular-neuronal (ICN)-Abs, neuronal-surface (NS)-Abs, aquaporin-4 (AQP4)-Abs, myelin oligodendrocyte glycoprotein (MOG)-Abs, myelin-associated glycoprotein (MAG)-Abs, ganglioside-Abs, acetylcholine-receptor (AChR)-Abs, and muscle-specific-kinase (MuSK)-Abs, and 34 laboratories. Assays were classified as tissue-based assays (TBAs), solid-phase assays (SPAs), liquid-phase assays (LPAs), and CBAs. Thirty-three samples were provided. Results: Three-quarter of the tests were commercial. Median accuracy for the laboratories was 75% (range 50-100). In 8/10 schemes, at least one sample provided discrepant results. Inter-laboratory "substantial agreement" was found in 6/10 schemes (AChR, MuSK, MAG, AQP4, MOG, and NS-Abs), whereas the worst agreements regarded OCBs and ganglioside-Abs. Both commercial and in-house assays performed better in experienced laboratories. Conclusions: Assays could be divided in (a) robust commercial tests with substantial inter-laboratory agreement (MAG-Abs; AChR- and MuSK-Abs); commercial/"in-house" tests with (b) partial inter-laboratory agreement (AQP4-Abs, MOG-Abs, NS-Abs, ICN-Abs), and (c) with large inter-laboratory disagreement (OCBs, ganglioside-Abs). This real-life snapshot of the neuroimmunology test performances highlights shortcomings attributable to technician-dependent performances, assay structural limitations, and errors in test interpretations.

Keywords: ELISA; antibodies; cell-based assays; external quality assessment scheme; neuroimmunology; radioimmunoassays; standardization; tissue-based assays.

Figures

Figure 1
Figure 1
Assays used in the AINI-EQA program. The figure considers the number laboratory using (A) either in house or commercial assays or (B) a specific assay type. A single laboratory could use more than one assay. MOG, myelin oligodendrocyte glycoprotein; NS, neuronal surface; AQP4, aquaporin 4; MuSK, muscle specific kinase; ICN, intracellular neuronal; IEF, isoelectric focusing. SPA, solid phase assay; CBA, cell-based assay; LPA, liquid-phase assay; TBA, tissue-based assay.
Figure 2
Figure 2
Laboratory performances and schemes results in AINI-EQA program. (A) Accuracy is represented by the number of concordant results obtained by each lab in all the schemes joined. Each lab participated to a variable number of schemes; (B,C) represent the performance (B) and the concordance of results (C) in each scheme (MAG and AChR schemes are not represented since all results were concordant). MOG, myelin oligodendrocyte glycoprotein; NS, neuronal surface; AQP4, aquaporin 4; MuSK, muscle specific kinase; ICN, intracellular neuronal; IEF, isoelectric focusing.

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