HLA‐B27 association of autoimmune encephalitis induced by PD‐L1 inhibitor

Abstract

Objective: While immune checkpoint inhibitors are increasingly used for various cancers, unpredictable immune-related adverse events (irAEs) such as autoimmune encephalitis is life-threatening. Here, we report an association between human leukocyte antigen (HLA) and atezolizumab-induced encephalitis. Methods: From an institutional prospective cohort for encephalitis, we identified patients with autoimmune encephalitis after the use of atezolizumab, a PD-L1 (programmed death-ligand 1) inhibitor, from August 2016 to September 2019 and analyzed their HLA genotypes. Results: A total of 290 patients received atezolizumab, and seven patients developed autoimmune encephalitis, and five of whom were enrolled for the analysis. The patients presented altered mentality, seizures, or myelitis. Three patients had the HLA-B*27:05 genotype in common (60%), which is significantly frequent given its low frequency in the general population (2.5%). After Bonferroni correction, HLA-B*27:05 was significantly associated with autoimmune encephalitis by atezolizumab (corrected P < 0.001, odds ratio 59, 95% CI = 9.0~386.9). Interpretation: Here we found that three in five patients with autoimmune encephalitis associated with atezolizumab had the rare HLA-B*27:05 genotype. Further systematic analyses in larger cohorts are necessary to investigate the value of HLA screening to prevent the life-threatening adverse events.

Atezolizumab-induced Encephalitis in a Patient with Hepatocellular Carcinoma: A Case Report and Literature Review

“…The difference in frequencies among individuals and races may be ascribed to a particular immunogenetic background. According to a Korean report, HLA-B*27:05 might be related to encephalitis induced by atezolizumab ( 13 ).…”

Acetylcholine receptor binding antibody–associated myasthenia gravis, myocarditis, and rhabdomyolysis induced by tislelizumab in a patient with colon cancer: A case report and literature review

“…Neurological irAEs are not associated with the brand of ICI. Nevertheless, atezolizumab can cause autoimmune encephalitis in Asian cancer patients at an unexpectedly high rate ( 86 , 87 ).…”

Nivolumab-associated DRESS in a genetic susceptible individual

“… 33 In this regard, different HLA molecules are reasonably able to enhance or repress specific T cell-mediated or antibody response to specific antigens. Indeed, HLA signature has been tightly correlated to either ICI therapy treatment response 34 35 or other irAEs, including pneumonitis, 33 encephalitis, 36 thyroid dysfunctions, 37 and adrenal insufficiency. 38 Given the exponential application of ICI therapy, HLA-typing assay may be valuable to screen genetic susceptible or potential beneficial individuals before ICIs treatment.…”