IgLON5 autoimmunity secondary to immune checkpoint inhibitor

IgLON5 autoimmunity is characterized by a diverse range of clinical presentations, including neuropsychiatric symptoms, sleep disturbances, gait instability, and bulbar symptoms, that are usually insidiously progressive. While some individuals with specific HLA haplotypes may be more susceptible to developing anti-IgLON5 disease, this antibody is typically not associated with a paraneoplastic etiology nor known to be induced by immune checkpoint inhibitors (ICI). We present a clinical and serological workup of a patient who developed symptoms of IgLON5 autoimmunity following treatment with pembrolizumab. He was found to have IgLON5 antibodies present in both the serum and cerebrospinal fluid, but he also expressed high-risk HLA haplotypes. This case suggests that immune checkpoint inhibitors (ICI) may promote the development of IgLON5 autoimmunity, particularly in those with high-risk HLA haplotyes. •ICI may contribute to the development of IgLON5 autoimmunity, especially in those with high-risk HLA haplotypes.•The growing utilization of ICI is anticipated to result in heightened frequency and an expanded spectrum of neurologic adverse events associated with ICI.•ICI may induce development of antibodies in cancer patients that are not typically associated with paraneoplastic neurologic syndrome.