Fatal X-linked lymphoproliferative disease type 1-associated limbic encephalitis with positive anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antibody.

Abstract

BACKGROUND:

X-linked lymphoproliferative disease type 1 (XLP1) is a rare monogenic immune dysregulation disorder caused by a deficiency of a signaling lymphocyte activation molecule-associated protein (SAP). While many patients with XLP1 present with fatal hemophagocytic lymphohistiocytosis upon Epstein Barr virus (EBV) infection, a small fraction present with limbic encephalitis in the absence of EBV infection. It is poorly understood why SAP deficiency may cause limbic encephalitis in XLP1.

CASE:

A 12-year-old boy presented with seizures, changes in personality, memory loss, and cognitive deficits during treatment for interstitial pneumonia. A diagnosis of limbic encephalitis was made. Despite treatment against CD8+ T cell-mediated autoimmunity with intravenous methylprednisolone, dexamethasone, intravenous immunoglobulin, plasma exchange, cyclosporine, weekly etoposide, mycophenolate mofetil, and adalimumab, encephalitis progressed until the patient died after one month of treatment intitiation. Post-mortem genetic testing revealed a de novo SH2D1A truncating mutation. Tests for EBV infection were negative. Initial spinal fluid revealed markedly elevated protein levels, mild pleocytosis, and elevation of two chemokines (C-X-C motif chemokine ligand [CXCL] 10 and CXCL 13). Moreover, initial spinal fluid was tested positive for anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) autoantibody.

DISCUSSION:

In XLP1-associated limbic encephalitis, anti-AMPAR autoantibody production by the dysregulated immune system due to SAP deficiency might be a pathogenic mechanism of central nervous system manifestations. In addition to the standard treatment for XLP1, targeted treatment against B-cell-mediated immunity might be indicated for patients with XLP1-associated limbic encephalitis.

• Authors: Satoru Ochiai, Itaru Hayakawa, Eri Ohashi, Sho Hamano, Yohane Miyata, Hiroshi Sakuma, Keita Hogetsu, Yoshihiro Gocho, Masao Ogura, Toru Uchiyama, Yuichi Abe
• Journal: Brain & development (Brain Dev) Vol. 44 Issue 9 Pg. 630-634 (Oct 2022) ISSN: 1872-7131 [Electronic] Netherlands
• PMID: 35778314 (Publication Type: Case Reports)
• Copyright: Copyright © 2022 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Anti-AMPAR antibody
• Autoantibodies
• alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

Topics

• Autoantibodies
• Child
• Epstein-Barr Virus Infections (complications)
• Herpesvirus 4, Human (genetics, metabolism)
• Humans
• Limbic Encephalitis
• Lymphoproliferative Disorders
• Male
• alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (metabolism)