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. 2023 Nov 15;11(1):e200182.
doi: 10.1212/NXI.0000000000200182. Print 2024 Jan.

Antibody Investigations in 2,750 Children With Suspected Autoimmune Encephalitis

Li-Wen Chen  1 , Mar Guasp  1 , Gemma Olivé-Cirera  1 , Eugenia Martínez-Hernandez  1 , Raquel Ruiz García  1 , Laura Naranjo  1 , Albert Saiz  1 , Thaís Armangue  1 , Josep Dalmau  2
Affiliations

Antibody Investigations in 2,750 Children With Suspected Autoimmune Encephalitis

Li-Wen Chen et al. Neurol Neuroimmunol Neuroinflamm. .

Abstract

Objectives: To assess the frequency and types of neuronal and glial (neural) antibodies in children with suspected autoimmune encephalitis (AE).

Methods: Patients younger than 18 years with suspected AE other than acute disseminated encephalomyelitis, whose serum or CSF samples were examined in our center between January 1, 2011, and April 30, 2022, were included in this study. Samples were systematically examined using brain immunohistochemistry; positive immunostaining was further investigated with cell-based assays (CBA), immunoblot, or live neuronal immunofluorescence.

Results: Of 2,750 children, serum or CSF samples of 542 (20%) showed brain immunoreactivity, mostly (>90%) against neural cell surface antigens, and 19 had antibodies only identified by CBA. The most frequent targets were N-methyl-d-aspartate receptor (NMDAR, 76%) and myelin oligodendrocyte glycoprotein (MOG, 5%), followed by glutamic acid decarboxylase 65 (2%) and γ-aminobutyric acid A receptor (2%). Antibodies against other known cell surface or intracellular neural antigens (altogether 6% of positive cases) and unknown antigens (9%) were very infrequent.

Discussion: The repertoire of antibodies in children with AE is different from that of the adults. Except for NMDAR and MOG antibodies, many of the antibodies included in diagnostic panels are rarely positive and their up-front testing in children seems unneeded.

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Conflict of interest statement

J. Dalmau holds patents for the use of Ma2, NMDAR, GABABR, GABAAR, DPPX and IgLON5 as autoantibody tests. J. Dalmau receives royalties related to autoantibody tests from Athena Diagnostics and Euroimmun, Inc. M. Guasp and G. Olivé-Cirera are recipients of a Rio Hortega grant (CM21/00016 and CM22/00066, respectively) from the Instituto de Salud Carlos III (ISCIII), Spain, cofinanced by Fondo Social Europeo Plus (FSE+). The rest of the authors have no conflicts of interest related to the submitted work. Go to Neurology.org/NN for full disclosures.

Figures

Figure 1
Figure 1. Approach to Neural Antibody Detection in Children With Autoimmune Encephalitis
All CSF samples were first examined with rat brain tissue immunohistochemistry (IHC), followed by cell-based assays (CBAs) or immunoblot according to the pattern of immunostaining. If CSF was negative, serum was used for the same assays. Antibodies not well detected with IHC (GlyR, D2R, and a subset of MOG antibodies) were assessed directly by CBAs (CSF for GlyR and D2R antibodies and serum and CSF for MOG antibodies). Samples showing neuropil immunostaining but negative by CBAs were examined with immunofluorescence on live hippocampal neurons to determine whether the target antigen was on the cell surface of neurons. Overall, 542 patients (20%) had serum and/or CSF antibodies detected by initial brain immunohistochemistry: they included 505 of 2,478 (20%) CSF samples and/or 293 of 1736 (17%) serum samples tested with this brain tissue assay (not shown). In a subset of 9 patients with MOG antibodies, the MOG-IgG reactivity was visible in brain tissue; paired serum/CSF samples were available from 8 of the patients: 5 showed reactivity in both samples and 3 only in serum.
Figure 2
Figure 2. Frequency of Neural Antibodies Detected in Children With Autoimmune Encephalitis
This pie chart represents the frequency and percentages of neural antibodies detected in the study. NSA = neural surface antigen.
See this image and copyright information in PMC

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