HLA-DR*04:05 is involved in the development of Vogt-Koyanagi-Harada disease-like immune-related adverse events in patients receiving immune checkpoint inhibitors
Purpose
Immune checkpoint inhibitors (ICIs) activate anti-tumor activity by inhibiting immune checkpoint molecules that suppress inflammatory T-cell activity. On the other hand, ICIs cause excessive immune responses called immune-related adverse events (irAEs), including uveitis (ICIU). Vogt-Koyanagi-Harada disease (VKH)-like uveitis is a common form of ICIU. In this study, we investigated which factors determined the disease form of ICIU.
Methods
In the present study, we retrospectively reviewed the medical records of nine ICIU cases treated with ICI for malignancies. In addition, we also performed HLA typing on seven cases to investigate the association between HLA and disease type. Fisher's exact test was applied for statistical analysis.
Results
Five of the ICIU cases were VKH-like ICIUs, and four were non-VKH-like ICIUs. No association was found between mean age, gender, primary disease, ICI, time to onset, uveitis, and disease type. Four of four patients with VKH-like ICIU who underwent HLA genotyping were positive for HLA-DR4*04:05, and three of three patients with non-VKH-like ICIU were negative for HLA-DR4*04:05. Statistical analysis showed that HLA-DR4*04:05 was significantly associated with developing VKH-like ICIU (P = 0.029).
Conclusion
In ICIU, HLA-DR4*04:05 was suggested to be a factor defining the pathogenesis of VKH-like uveitis, suggesting that ICI-associated VKH-like uveitis shares similar pathogenesis with VKH.
Conflict of interest
No
Authors 1
Last name
TAKEUCHI
Initials of first name(s)
M
Department
Ophthalmology and Visual Science
City
Yokohama
Country
Japan
Authors 2
Last name
Meguro
Initials of first name(s)
A
Department
Ophthalmology and Visual Science
City
Yokohama
Country
Japan
Authors 3
Last name
Chikagawa
Initials of first name(s)
R
Department
Ophthalmology and Visual Science
City
Yokohama
Country
Japan
Authors 4
Last name
Osada
Initials of first name(s)
R
Department
Ophthalmology and Visual Science
City
Yokohama
Country
Japan
Authors 5
Last name
Shibuya
Initials of first name(s)
E
Department
Ophthalmology and Visual Science
City
Yokohama
Country
Japan
Authors 6
Last name
Hasumi
Initials of first name(s)
Y
Department
Ophthalmology and Visual Science
City
Yokohama
Country
Japan
Authors 7
Last name
Ishihara
Initials of first name(s)
M
Department
Ophthalmology and Visual Science
City
Yokohama
Country
Japan
Authors 8
Last name
Mizuki
Initials of first name(s)
N
Department
Ophthalmology and Visual Science
City
Yokohama
Country
Japan
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