Background/Purpose:  Antibodies directed against N-methyl-D-aspartate type glutamate receptor (NMDAR), voltage-gated potassium channel (VGKC) or glutamic acid decarboxylase (GAD65) are frequently associated with autoimmune encephalitis (AE) in pediatric patients. Yet, the full repertoire of the autoantibody diversity in children remains poorly defined.

Methods:  Eighty-eight consecutive patient samples (59 sera and 29 CSF) received at ARUP Laboratories from Intermountain Healthcare’s Primary Children’s Medical Center, Salt Lake City, Utah and Texas Children’s Hospital, Houston, Texas for evaluation for NMDAR (cell based assays, CBA), VGKC (radioimmunoprecipitation), or GAD65 (enzyme immunoassay) antibodies were identified over a period of 12 months. Residual volume of patient samples were evaluated on a research basis by indirect immunofluorescence technique (IIFT) using cerebellum (monkey and rat), intestine (monkey), peripheral nerve and pancreas tissue sections for neuronal nuclear, Purkinje cell cytoplasmic, myelin, non-medullated and astrocyte autoantibodies (PNS Mosaic IFFT), and an CBA for Delta notch-like epidermal growth factor-related receptor (DNER). In addition, the AE mosaic IIFT with hippocampus (rat) tissue and CBA to detect antibodies to NMDAR, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), gamma amino butyric acid type B receptor (GABA_bR), leucine-rich glioma inactivated 1 (LGI1), contactin associated protein-2 (CASPR-2), dipeptidyl-peptidase-like protein-6 (DPPX-6), and glycine receptor (GlyR) was utilized. This study was conducted in accordance with a University of Utah Institutional Review Board approved protocol and in compliance with ARUP policies.

Results:  Samples were received from 60 unique patients including 32 females (median age 11.8; range 0-19 years) and 28 males (median age 9.0; range 0-18 years). Antibodies were detected in 30/60 patients (50%); 23 with single antibodies and 7 subjects with 2 or more antibodies. NMDAR antibody was the most prevalent (n=15) followed by GAD65 (n=7), VGKC (n=6), non-medullated (n=4), Purkinje cell (n=3), myelin (n=3), and astrocyte (n=1) antibodies. Of the 28 patients with paired serum and CSF, 16 possessed autoantibodies; 8 NMDAR-positive (7 seropositive, 8 CSF positive), and 5 GAD65- and 4 VGKC-seropositive only. Eighty percent (24/30) of the antibody-positive patients in our cohort had NMDAR, GAD65 and/or VGKC antibodies; however, a sizable number of patients possessed autoantibodies not typically associated with pediatric AE.

Conclusion:   Overall, NMDAR, GAD and VGKC autoantibodies were the most prevalent antibodies detected in this two center pediatric cohort of samples analyzed at a large referral lab. Prevalence of these antibodies approximates previous reports in the pediatric literature. Additional autoantibodies targeting diverse proteins and associated neurologic functions were also detected demonstrating a need for the validation of additional markers for pediatric AE such as the Purkinje cell and nerve (i.e. non-medullated nerve and myelin) autoantibodies detected in this cohort of patients.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/autoantibody-diversity-in-pediatric-patients-undergoing-evaluation-for-autoimmune-encephalitis-a-retrospective-investigation/