Whole-exome sequencing shows no specific mutation in ovarian teratoma of NMDAR-antibody encephalitis (P5-5.003)

Abstract

<h3>Objective:</h3> To investigate mutations specific to the N-methyl-D-aspartate receptor (NMDAR)-associated teratoma to reveal the autoimmunity mechanism <h3>Background:</h3> N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis is the most common form of autoimmune encephalitis, about 40% of which is caused by ovarian teratoma. However, it is unknown why only a small population of ovarian teratoma causes the autoimmunity while the majority of the teratoma don’t. This study aimed to investigate any driver mutations specific to the NMDAR-associated teratoma to reveal the autoimmunity mechanism. <h3>Design/Methods:</h3> We included 17 ovarian teratomas derived from 15 patients with NMDAR-antibody encephalitis and 18 control ovarian teratoma from 30 patients without encephalitis. All the samples were genotyped by the SureSelect V6-Post Exome Capture kit (Agilent, CA, USA). The exome data were analyzed with R version 4.06 (Vienna, Austria) and the MUTALISK program (National cancer center, Goyang-si, Korea). <h3>Results:</h3> The two groups with and without NMDAR-antibody encephalitis had a mean age of 23.9 and 24.4 years, respectively. The average teratoma size was smaller in the group with encephalitis (3.0±2.1 cm vs 10.9±2.1, respectively). With the criteria lower than 1% of allele frequency with 1000 genome phase 3 (1000Gp3) and the Exome Aggregation Consortium (ExAC), 34 exomes were passed in our samples. Of these, no exome showed significantly different mutations between the groups of teratoma with and without NMDAR-antibody encephalitis. From the MUTALISK analysis, there was no significant difference in the mutation pattern signature in exomes between the two groups. <h3>Conclusions:</h3> This study shows that there is no difference in the mutation profile in protein-coding genes between the ovarian teratoma causing NMDAR-antibody encephalitis and the control teratoma. This result implies that post-transcriptional immune pathogeneses are involved in the autoimmune recognition of ovarian teratoma with NMDAR-antibody encephalitis. <b>Disclosure:</b> Dr. Jang has nothing to disclose. Dr. Ahn has nothing to disclose. Mr. Lee has nothing to disclose. Prof. PARK has nothing to disclose. Prof. Lee has nothing to disclose. Prof. Chu has nothing to disclose. Dr. Lee has nothing to disclose. Prof. Won has nothing to disclose. Prof. Lee has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Advanced Neural Technologies. Prof. Lee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biofire Diagnostics. Prof. Lee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Prof. Lee has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GC pharma. The institution of Prof. Lee has received research support from GC pharma.