Comparison of N-methyl-d-aspartate receptor antibody assays using live or fixed substrates

被引:12
作者
Thouin, Anais [1 ]
Gastaldi, Matteo [2 ]
Woodhall, Mark [3 ]
Jacobson, Leslie [3 ]
Vincent, Angela [3 ]
机构
[1] Newcastle Upon Tyne Hosp NHS Fdn Trust, Neurol Dept, Newcastle Upon Tyne, Tyne & Wear, England
[2] Univ Pavia, IRCCS Natl Neurol Inst Mondino, Pavia, Italy
[3] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci, Oxford, England
关键词
NMDAR antibody encephalitis; Cell based assays; Immunohistochemistry; Neuroimmunology; Antibody detection; 1ST-EPISODE PSYCHOSIS; ENCEPHALITIS; AUTOANTIBODIES; PREVALENCE; DIAGNOSIS;
D O I
10.1007/s00415-020-10329-0
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The diagnostic criteria for N-methyl-d-aspartate receptor antibody (NMDAR-Ab) encephalitis require the presence of CSF antibodies against the NMDAR, whereas serum antibodies are considered specific only if accompanied by CSF antibodies. Current assays include in-house immunochemistry (IHC), or cell-based assays (CBA) which use live (L-CBA) or fixed cells (F-CBA), and commercially available fixed-cells CBA (C-CBA), but these have not been compared in parallel. We compared the L-CBA with F-CBA, C-CBA, and IHC using sera and CSFs archived from > 30,000 received for testing and previously positive by L-CBA. Referring neurologists, if identified, provided "definite" or "unlikely" diagnoses of NMDAR-Ab encephalitis for 31 paired serum-CSF samples and 53 unpaired sera. There was good concordance between paired sera and CSFs, with 13/16 "definite" pairs positive, and 7/8 "unlikely" pairs negative in all in-house assays. In unpaired "definite" sera, L-CBA was most sensitive. However, 19/24 serum samples from "unlikely" patients were positive by L-CBA, with only 5/24 and 1/24 positive by F-CBA and IHC, respectively. In available samples, C-CBA demonstrated high sensitivity for CSF, but surprisingly low sensitivity for serum. Overall, regardless of the technique, CSF results were accurate and easy to interpret, but if CSF is unavailable, negative serum C-CBA results in cases with suspected NMDAR-Ab encephalitis could be repeated by a more sensitive in-house assay. Although these assays are sensitive, particularly for CSF, referral of sera with low pre-test probability should be avoided to reduce clinically-irrelevant "false positive" results.
引用
收藏
页码:1818 / 1826
页数:9
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