Recognition of Neuronal Surface Antigen-Specific Immunostaining Pattern Facilitates Identification of Target Antigens in Autoimmune Encephalitis
Takahiro Iizuka1, Naomi Kanazawa1, Naomi Nagata1, Hitomi Nakagawa1, Hiroki Suga2, Hiroya Ohara3, Tomomi Iwami1, Masaki Iizuka1, Juntaro Kaneko1, Eiji Kitamura1, Kazutoshi Nishiyama1
1Department of Neurology, Kitasato University School of Medicine, 2Department of Neurology, Showa General Hospital, 3Department of Neurology, Minami-Nara General Medical Center
Objective:
To make a positive control panel using a commercial rat brain immunohistochemistry (c-IHC) to estimate neuronal surface (NS) antigens.
Background:
IHC is usually performed at research laboratories to screen NS antibodies (NS-abs) in suspected autoimmune encephalitis but not to determine NS antigens while cell-based assay (CBA) is performed to determine the target antigens. Commercial fixed CBA (c-CBA) has increasingly been used but not available for all NS antigens. In clinical practice, it is difficult to examine all potentially causative NS antigens with c-CBA because of the high cost. We previously reported several NS antigen-specific immunostaining patterns to estimate target antigens quickly.
Design/Methods:
Among 777 patients tested for NS-abs at Dalmau’s Lab (Barcelona) between Jan. 2007 and Sep. 2024, 437, whose CSF samples were examined with c-IHC at Kitasato University, were included. After exclusion of 301 patients (289 with no NS-abs in CSF, 5 with only GlyR-ab, 4 with more than one NS-ab, and 3 with high GAD65-abs), we reviewed the immunostaining patterns in the remaining 136 NS-ab-positive patients’ CSF to revise the positive control panel.
Results:
Various neuropil patterns of different intensities were seen in 93 patients (68%): NMDAR (57/81, 70%), LGI1 (15/18, 83%), GABAaR (5/12, 42%), AMPAR (5/8, 63%), GABAbR (2/5, 40%), GluK2 (1/1), mGluR1 (1/1), mGluR5 (1/1), Caspr2 (1/1), amphiphysin (1/1), and NS antigens not characterized yet (n=4/7). We found a distinctive immunostaining pattern specific for individual NS antigen in the hippocampus and cerebellum, and a novel staining pattern corresponding to probably novel antigens.
Conclusions:
Neuropil pattern is not always visually identified on c-IHC despite the presence of NS-abs in CSF; thus, clinicians should aware that neuropil pattern may be missed when being examined with only c-IHC. However, if there is apparent neuropil pattern, it will help identify the target NS antigen by choosing CBA expressing the target antigen appropriately.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.