PT  - JOURNAL ARTICLE
AU  - Antonio Farina
AU  - Macarena Villagrán-García
AU  - Nicolás Lundahl Ciano-Petersen
AU  - Alberto Vogrig
AU  - Sergio Muñiz-Castrillo
AU  - Luc Taillandier
AU  - Maud Michaud
AU  - Mathilde Lefilliatre
AU  - Adrien Wang
AU  - Zoe Lepine
AU  - Géraldine Picard
AU  - Valentin Wucher
AU  - Maroua Dhairi
AU  - Nicole Fabien
AU  - David Goncalves
AU  - Véronique Rogemond
AU  - Bastien Joubert
AU  - Jèrôme Honnorat
TI  - Anti-Hu Antibodies in Patients With Neurologic Side Effects of Immune Checkpoint Inhibitors
AID  - 10.1212/NXI.0000000000200058
DP  - 2023 Jan 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e200058
VI  - 10
IP  - 1
4099  - http://nn.neurology.org/content/10/1/e200058.short
4100  - http://nn.neurology.org/content/10/1/e200058.full
SO  - Neurol Neuroimmunol Neuroinflamm2023 Jan 01; 10
AB  - Background and Objectives To clinically characterize post–immune checkpoint inhibitor (ICI) Hu antibody (Ab) neurologic disorders, we analyzed Hu-Ab–positive patients with neurologic immune-related adverse events (n-irAEs) and compared them with patients with other n-irAEs, ICI-naive patients with Hu-Ab paraneoplastic neurologic syndromes (PNSs) identified in the same study center, and those with Hu-Ab n-irAEs reported elsewhere.Methods Patients whose samples were sent to the French reference center for a suspicion of n-irAE (2015–2021) were identified; those with a final diagnosis of n-irAE and Hu-Ab were included. Control groups included patients with a final diagnosis of n-irAE occurring during the same period as the patients included (2018–2021) but without Hu-Ab, and ICI-naive patients with Hu-Ab PNS diagnosed during the same period; a systematic review was performed to identify previous reports.Results Eleven patients with Hu-Ab and n-irAEs were included (median age, 66 years, range 44–76 years; 73% men). Ten patients had small cell lung cancer, and 1 had lung adenocarcinoma. The median follow-up from onset was 3 months (range 0.5–18 months). Compared with those with other n-irAEs (n = 63), Hu-Ab–positive patients had more frequently co-occurring involvement of both central and peripheral nervous systems (36% vs 8%, p = 0.02) and limbic (54% vs 14%, p < 0.01), brainstem (27% vs 5%, p = 0.02), and dorsal root ganglia (45% vs 5%, p < 0.01) involvement. The proportion of patients with severe disability (modified Rankin Scale score >3) at diagnosis was higher among Hu-Ab n-irAEs (91% vs 52%, p = 0.02). Patients with Hu-Ab had also poorer outcome (100% vs 28%, p < 0.01) and higher mortality (91% vs 46%, p < 0.01). There was no significant difference in terms of clinical features between Hu-Ab n-irAEs and ICI-naive Hu-Ab PNS (n = 92), but there was a poorer outcome (56/78, 71%, p < 0.01) and higher mortality (26%, p < 0.01) among the former. No significant difference was found between the patients reported herein and those in the literature.Discussion The presence of Hu-Ab identifies a subgroup of n-irAEs that consistently reproduce the phenotypes of Hu-Ab-related PNS, supporting the hypothesis of ICI triggering or unmasking PNS. As these patients show high disability and mortality, further studies are required to investigate the underlying immunopathogenic mechanisms and to improve the outcome of Hu-Ab n-irAEs.CTLA4=cytotoxic T-lymphocyte-associated protein 4; DRG=dorsal root ganglia; Hu-ab=Hu antibody; ICI=immune checkpoint inhibitor; LE=limbic encephalitis; mRS=modified Rankin Scale; n-irAE=neurologic immune-related adverse event; NCS=nerve conduction study; PD1=programmed cell death protein 1; PDL1=programmed death-ligand 1; PNS=paraneoplastic neurologic syndrome; SNN=sensory neuronopathy