Anti-Hu Antibodies in Patients With Neurologic Side Effects of Immune Checkpoint Inhibitors
Antonio Farina, Macarena Villagrán‐García, Nicolás Lundahl Ciano-Petersen, Alberto Vogrig, Sergio Muñiz‐Castrillo, Luc Taillandier, Maud Michaud, Mathilde Lefilliatre, Adrien Wang, Zoe Lepine, Géraldine Picard, Valentin Wucher, Maroua Dhairi, Nicole Fabien, David Gonçalves, Véronique Rogemond, Bastien Joubert, Jérôme Honnorat
Abstract
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: < 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.