Expanding the clinical spectrum of anti-DPPX encephalitis: a multicenter retrospective study

Yining Gao; Yizongheng Zhang; Hangxing Chunyu; Yongfeng Xu; Ying Wang; Suzhi Liu; Jie Chang; Bo Tang; Congying Xu; Yi Lu; Jian Zhou; Xiangyong Kong; Xiaoying Zhu; Sheng Chen; Qinming Zhou; Huanyu Meng

doi:10.3389/fnins.2024.1379933

Expanding the clinical spectrum of anti-DPPX encephalitis: a multicenter retrospective study

Front Neurosci. 2024 May 2:18:1379933. doi: 10.3389/fnins.2024.1379933. eCollection 2024.

Authors

Yining Gao^#¹, Yizongheng Zhang^#¹, Hangxing Chunyu², Yongfeng Xu³, Ying Wang⁴, Suzhi Liu⁴, Jie Chang⁵, Bo Tang⁶, Congying Xu⁷, Yi Lu⁸, Jian Zhou⁹, Xiangyong Kong¹⁰, Xiaoying Zhu¹¹, Sheng Chen¹, Qinming Zhou¹, Huanyu Meng¹

Affiliations

¹ Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China.
⁴ Department of Neurology, Taizhou Hospital of Zhejiang Province, Zhejiang, China.
⁵ Department of Neurology, Huadong Hospital Affiliated to Fudan University, Shanghai, China.
⁶ Department of Neurology, Affiliated Hangzhou First People's Hospital School of Medicine, Westlake University, Hangzhou, Zhejiang, China.
⁷ Department of Neurology, The Second Hospital of Jiaxing, Jiaxing, Zhejiang, China.
⁸ Department of Neurology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.
⁹ Department of Pediatrics, The First People's Hospital of Yongkang, Yongkang, China.
¹⁰ Department of Neurology, Yongkang Traditional Chinese Medicine Hospital, Zhejiang, China.
¹¹ Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

^# Contributed equally.

Abstract

Objective: Anti-dipeptidyl-peptidase-like protein-6 (DPPX) encephalitis is a rare autoimmune encephalitis, and clinical and experimental information regarding this disease is limited. We conducted this study to comprehensively describe the clinical characteristics, ancillary test results, neuroimaging results, and treatment response in a group of Chinese patients with anti-DPPX encephalitis for better understanding this disease.

Methods: We recruited 14 patients who tested positive for anti-DPPX antibodies in the serum and/or cerebrospinal fluid from 11 medical centers between March 2021 and June 2023. This retrospective study evaluated data on symptoms, autoantibody test, auxiliary examinations, treatments, and outcomes.

Results: The average age at diagnosis was 45.93 ± 4.62 years (range: 11-72 years), and 9 of the 14 patients were males. The main symptoms included cognitive impairment (50.0%, 7/14), central nervous system hyperexcitability (42.9%, 6/14), gastrointestinal dysfunction (35.7%, 5/14), and psychiatric disorders (35.7%, 5/14). Notably, we discovered specific findings on ¹⁸F-fluorodeoxyglucose positron-emission tomography (PET)/magnetic resonance imaging in two patients. Co-existing autoantibodies were identified in two patients. Parainfection was identified in four patients. One patient had other autoimmune diseases, and one had tumor. Eleven patients received immunotherapy and most patients improved at discharge. Surprisingly, three male patients but no female patients relapsed during the 6 months of follow-up.

Conclusion: The development and outcome of anti-DPPX encephalitis are variable. Male patients were predominant in our cohort. The most common symptoms were the classical triad of prodromal gastrointestinal dysfunction, cognitive and mental disorders, and central nervous system hyperexcitability. Infections, immune dysregulation, and tumors may be important etiologies. Long-term monitoring of disease development should be done in male patients. Overall, our results highlight novel clinical characteristics of anti-DPPX encephalitis.

Keywords: anti-DPPX antibody; anti-DPPX encephalitis; clinical characteristic; immunotherapy; multicenter.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was funded by the National Natural Science Foundation of China (82201558).