The immunobiology of herpes simplex virus encephalitis and post-viral autoimmunity.
Jonathan CleaverKatie JefferyPaul KlenermanMing LimLahiru HandunnetthiSarosh R IraniAdam E HandelPublished in: Brain : a journal of neurology (2023)
Herpes simplex virus encephalitis (HSE) is the leading cause of non-epidemic encephalitis in the developed world and, despite antiviral therapy, mortality and morbidity is high. The emergence of post-HSE autoimmune encephalitis (AE) reveals a new immunological paradigm in autoantibody-mediated disease. A reductionist evaluation of the immunobiological mechanisms in HSE is crucial to dissect the origins of post-viral autoimmunity and supply rational approaches to the selection of immunotherapeutics. Herein, we review the latest evidence behind the phenotypic progression and underlying immunobiology of HSE including the cytokine/chemokine environment, the role of pathogen-recognition receptors, T- and B-cell immunity and relevant inborn errors of immunity. Secondly, we provide a contemporary review of published patients with post-HSE AE from a combined cohort of 110 patients. Thirdly, we integrate novel mechanisms of autoimmunisation in deep cervical lymph nodes to explore hypotheses around post-HSE AE and challenge these against mechanisms of molecular mimicry and others. Finally, we explore translational concepts where neuroglial surface autoantibodies have been observed with other neuroinfectious diseases and those that generate brain damage including traumatic brain injury, ischaemic stroke and neurodegenerative disease. Overall, the clinical and immunological landscape of HSE is an important and evolving field, from which precision immunotherapeutics could soon emerge.
Keyphrases
- herpes simplex virus
- traumatic brain injury
- lymph node
- sars cov
- type diabetes
- newly diagnosed
- systemic lupus erythematosus
- emergency department
- multiple sclerosis
- coronary artery disease
- prognostic factors
- cardiovascular events
- early stage
- blood brain barrier
- single cell
- rectal cancer
- sentinel lymph node
- neoadjuvant chemotherapy
- locally advanced