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

Matteo Gastaldi; Elisabetta Zardini; Silvia Scaranzin; Antonio Uccelli; Francesca Andreetta; Fulvio Baggi; Diego Franciotta

doi:10.3389/fneur.2019.01385

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

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

Authors

Matteo Gastaldi¹, Elisabetta Zardini^{1

2}, Silvia Scaranzin¹, Antonio Uccelli^{3

4}, Francesca Andreetta⁵, Fulvio Baggi⁵, Diego Franciotta¹

Affiliations

¹ Neuroimmunology Laboratory, IRCCS Mondino Foundation, Pavia, Italy.
² Department of Brain and Behavioral Science, University of Pavia, Pavia, Italy.
³ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy.
⁴ Ospedale Policlinico San Martino - IRCCS, Genoa, Italy.
⁵ UO Neurology IV, IRCCS Fondazione Istituto Neurologico Carlo Besta, Milan, Italy.

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.