PMID- 33031633
OWN - NLM
STAT- MEDLINE
DCOM- 20210924
LR  - 20240330
IS  - 2328-9503 (Electronic)
IS  - 2328-9503 (Linking)
VI  - 7
IP  - 11
DP  - 2020 Nov
TI  - HLA-B27 association of autoimmune encephalitis induced by PD-L1 inhibitor.
PG  - 2243-2250
LID - 10.1002/acn3.51213 [doi]
AB  - 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.
CI  - (c) 2020 The Authors. Annals of Clinical and Translational Neurology published by 
      Wiley Periodicals LLC on behalf of American Neurological Association.
FAU - Chang, Hyeyeon
AU  - Chang H
AUID- ORCID: 0000-0001-6939-7913
AD  - Department of Neurology, Seoul National University Hospital, Seoul, Republic of 
      Korea.
AD  - Department of Neurology, Konyang University Hospital, Deajeon, Republic of Korea.
FAU - Shin, Yong-Won
AU  - Shin YW
AUID- ORCID: 0000-0002-6781-7782
AD  - Department of Neurology, Seoul National University Hospital, Seoul, Republic of 
      Korea.
AD  - Center for Hospital Medicine, Seoul National University Hospital, Seoul, Republic 
      of Korea.
AD  - Department of Neurosurgery, Seoul National University Hospital, Seoul, Republic 
      of Korea.
FAU - Keam, Bhumsuk
AU  - Keam B
AUID- ORCID: 0000-0001-8196-4247
AD  - Department of Internal Medicine, Seoul National University Hospital, Cancer 
      Research Institute, Seoul National University College of Medicine, Seoul, 
      Republic of Korea.
FAU - Kim, Miso
AU  - Kim M
AUID- ORCID: 0000-0002-4064-4199
AD  - Department of Internal Medicine, Seoul National University Hospital, Cancer 
      Research Institute, Seoul National University College of Medicine, Seoul, 
      Republic of Korea.
FAU - Im, Seock-Ah
AU  - Im SA
AUID- ORCID: 0000-0002-5396-6533
AD  - Department of Internal Medicine, Seoul National University Hospital, Cancer 
      Research Institute, Seoul National University College of Medicine, Seoul, 
      Republic of Korea.
FAU - Lee, Soon-Tae
AU  - Lee ST
AUID- ORCID: 0000-0003-4767-7564
AD  - Department of Neurology, Seoul National University Hospital, Seoul, Republic of 
      Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201008
PL  - United States
TA  - Ann Clin Transl Neurol
JT  - Annals of clinical and translational neurology
JID - 101623278
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (HLA-B27 Antigen)
RN  - 0 (Immune Checkpoint Inhibitors)
RN  - 52CMI0WC3Y (atezolizumab)
SB  - IM
MH  - Adult
MH  - Antibodies, Monoclonal, Humanized/*adverse effects
MH  - Autoimmune Diseases of the Nervous System/*chemically induced/genetics
MH  - Encephalitis/*chemically induced/genetics
MH  - Female
MH  - HLA-B27 Antigen/*genetics
MH  - Humans
MH  - Immune Checkpoint Inhibitors/*adverse effects
MH  - Male
MH  - Neoplasms/*drug therapy
MH  - Prospective Studies
PMC - PMC7664281
COIS- Patent pending for the HLA analysis to predict CNS-irAE (H.C., and S.-T.L.). 
      Seock-Ah Im received a research grant from AstraZeneca, Pfizer and Roche outside 
      of the current work and have advisory role for AstraZeneca, Amgen, Eisai, Hanmi 
      Corp. Lilly, Novartis, Pfizer, and Roche outside of the current work. Soon-Tae 
      Lee have an advisory role for Ono Pharmaceuticals and received research grants 
      from GC Pharma outside of the current work.
EDAT- 2020/10/09 06:00
MHDA- 2021/09/25 06:00
PMCR- 2020/10/08
CRDT- 2020/10/08 17:15
PHST- 2020/04/29 00:00 [received]
PHST- 2020/08/26 00:00 [revised]
PHST- 2020/09/12 00:00 [accepted]
PHST- 2020/10/09 06:00 [pubmed]
PHST- 2021/09/25 06:00 [medline]
PHST- 2020/10/08 17:15 [entrez]
PHST- 2020/10/08 00:00 [pmc-release]
AID - ACN351213 [pii]
AID - 10.1002/acn3.51213 [doi]
PST - ppublish
SO  - Ann Clin Transl Neurol. 2020 Nov;7(11):2243-2250. doi: 10.1002/acn3.51213. Epub 
      2020 Oct 8.