Reader response: Increased frequency of anti-Ma2 encephalitis associated with immune checkpoint inhibitors
Ahmed Z.Obeidat, Neurologist, Department of Neurology, Medical College of Wisconsin
Submitted September 07, 2019
I read with interest the article by Vogrig et al.1 The authors noted an increase in clinical cases of anti-Ma2 encephalitis in France coinciding with the introduction of immune checkpoint inhibitors (ICIs) for the treatment of specific cancers that can be associated with anti-Ma2 syndromes.1,2 The authors described an association and suggested a possible causality, acknowledging the limitations of the study. Interestingly, in case #2, testing detected “subclinical" anti-Ma2 before the use of ICIs. There was no available pre-ICI serology on the other patients.
It could be hypothesized that all six patients had pre-ICI subclinical anti-Ma2 seropositivity. If that was the case, then, considering the ICIs’ mechanism of action, the use of ICIs could trigger/aggravate the clinical syndrome rather than causing it.2,3 Patients with anti-Ma2 encephalitis exhibit unusual neurological symptoms that often result in diagnostic delay, and mild non-specific symptoms can precede diagnosis (personal experience).1,2
CD8+ T-cell infiltration into the CNS is a major finding in anti-Ma2 encephalitis and ICIs are known to oppose CD8+ T-cell suppression.2,3,4 This suggests that the use of ICIs in patients with circulating anti-Ma2 (before treatment) may trigger/worsen/unmask the neurologic syndrome by opposing CD8+ T-cell suppression among other immune effects as detailed by the authors.
Disclosure
The author reports no relevant disclosures. Contact journal@neurology.org for full disclosures.
References
Vogrig A, Fouret M, Joubert B, et al. Increased frequency of anti-Ma2 encephalitis associated with immune checkpoint inhibitors. Neurol Neuroimmunol Neuroinflamm 2019;6:e604.
Dalmau J, Graus F, Villarejo A, et al. Clinical analysis of anti-Ma2-associated encephalitis. Brain 2004;127:1831–1844.
Pfannenstiel LW, Diaz-Montero CM, Tian YF, et al. Immune-checkpoint blockade opposes CD8+ T-cell suppression in human and murine Cancer. Cancer Immunology Res 2019;7:510–525.
Bien CG, Vincent A, Barnett MH, et al. Immunopathology of autoantibody-associated encephalitides: clues for pathogenesis. Brain 2012;135:1622–1638.
I read with interest the article by Vogrig et al.1 The authors noted an increase in clinical cases of anti-Ma2 encephalitis in France coinciding with the introduction of immune checkpoint inhibitors (ICIs) for the treatment of specific cancers that can be associated with anti-Ma2 syndromes.1,2 The authors described an association and suggested a possible causality, acknowledging the limitations of the study. Interestingly, in case #2, testing detected “subclinical" anti-Ma2 before the use of ICIs. There was no available pre-ICI serology on the other patients.
It could be hypothesized that all six patients had pre-ICI subclinical anti-Ma2 seropositivity. If that was the case, then, considering the ICIs’ mechanism of action, the use of ICIs could trigger/aggravate the clinical syndrome rather than causing it.2,3 Patients with anti-Ma2 encephalitis exhibit unusual neurological symptoms that often result in diagnostic delay, and mild non-specific symptoms can precede diagnosis (personal experience).1,2
CD8+ T-cell infiltration into the CNS is a major finding in anti-Ma2 encephalitis and ICIs are known to oppose CD8+ T-cell suppression.2,3,4 This suggests that the use of ICIs in patients with circulating anti-Ma2 (before treatment) may trigger/worsen/unmask the neurologic syndrome by opposing CD8+ T-cell suppression among other immune effects as detailed by the authors.
Disclosure
The author reports no relevant disclosures. Contact journal@neurology.org for full disclosures.
References