臨床眼科76巻13号

2022年12月発行

特集 ゲノム解析の「今」と「これから」—解析結果は眼科診療に何をもたらすか

重篤な眼合併症を伴うStevens-Johnson症候群のゲノム解析による病態解明

著者： 上田真由美¹

所属機関： ¹京都府立医科大学眼科学教室

ページ範囲：P.1680 - P.1690

文献概要

●重篤な眼合併症・眼後遺症を伴うSJS/TEN（広義のStevens-Johnson症候群）の原因候補薬としては，アセトアミノフェンなどの解熱鎮痛薬を含んだ感冒薬が最も頻度が高い。

●日本人感冒薬関連眼合併症型SJSの発症にはHLA-A^＊02：06，HLA-B^＊44：03が関連する。

●その他の疾患関連遺伝子にTLR3，PTGER3，IKZF1などがあり，それらの遺伝子間相互作用が病態につよく関与している。

参考文献

1）上田真由美：眼科におけるStevens-Johnson症候群の病型ならびに遺伝素因．あたらしい眼科32：59-67，2015

2）上田真由美：重篤な眼合併症と伴うStevens-Johnson症候群の発症予測．あたらしい眼科33：501-510，2016

3）Lee HS, Ueta M, Kim MK et al：Analysis of ocular manifestation and genetic association of allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in South Korea. Cornea 35：199-204, 2016

5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A 102：4134-4139, 2005

5）Lonjou C, Borot N, Sekula P et al：A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs. Pharmacogenet Genomics 18：99-107, 2008

6）Tohkin M, Kaniwa N, Saito Y et al：A whole-genome association study of major determinants for allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients. Pharmacogenomics J 13：60-69, 2013

7）Chung WH, Hung SI, Hong HS et al：Medical genetics：a marker for Stevens-Johnson syndrome. Nature 428：486, 2004

3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med 364：1134-1143, 2011

3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in Japanese population. Hum Mol Genet 20：1034-1041, 2011

44：03 with cold medicine-related Stevens-Johnson syndrome with severe mucosal involvement. Sci Rep. doi：10.1038/srep04862, 2014

with cold medicine-related Stevens-Johnson syndrome with severe ocular surface complications. Sci Rep. doi：10.1038/srep05981, 2014

07：01 haplotype and cold medicine-related Stevens-Johnson syndrome with severe ocular complications in Thailand. Br J Ophthalmol 102：1303-1307, 2018

13）Ueta M, Kinoshita S：Ocular surface inflammation is regulated by innate immunity. Prog Retin Eye Res 31：551-575, 2012

14）Ueta M, Uematsu S, Akira S et al：Toll-like receptor 3 enhances late-phase reaction of experimental allergic conjunctivitis. J Allergy Clin Immunol 123：1187-1189, 2009

15）Nakamura N, Tamagawa-Mineoka R, Ueta M et al：Toll-like receptor 3 increases allergic and irritant contact dermatitis. J Invest Dermatol 135：411-417, 2015

16）Ueta M, Sotozono C, Nakano M et al：Association between prostaglandin E receptor 3 polymorphisms and Stevens-Johnson syndrome identified by means of a genome-wide association study. J Allergy Clin Immunol 126：1218-1225, 2010

17）Ueta M, Matsuoka T, Narumiya S et al：Prostaglandin E receptor subtype EP3 in conjunctival epithelium regulates late-phase reaction of experimental allergic conjunctivitis. J Allergy Clin Immunol 123：466-471, 2009

18）Kunikata T, Yamane H, Segi E et al：Suppression of allergic inflammation by the prostaglandin E receptor subtype EP3. Nat Immunol 6：524-531, 2005

19）Honda T, Matsuoka T, Ueta M et al：Prostaglandin E（2）-EP（3）signaling suppresses skin inflammation in murine contact hypersensitivity. J Allergy Clin Immunol 124：809-818, 2009

20）Ueta M, Sotozono C, Yokoi N et al：Prostaglandin E receptor subtype EP3 Expression in Human Conjunctival Epithelium and Its Changes in Various Ocular Surface Disorders. PLoS One. doi：10.1371/journal.pone.0025209, 2011

, for cold medicine-related Stevens-Johnson Syndrome/toxic epidermal necrolysis with severe mucosal involvements. J Allergy Clin Immunol 135：1538-1545, e17, 2015

22）Ueta M, Hamuro J, Nishigaki H et al：Inflammation in the Ikaros Family Zinc Finger 1（IKZF1）-keratin 5 specifc transgenic mice. Allergy 73：395-404, 2018

23）Ueta M, Tamiya G, Tokunaga K et al：Epistatic interaction between Toll-like receptor 3（TLR3）and prostaglandin E receptor 3（PTGER3）genes. J Allergy Clin Immunol 129：1413-1416, 2012

0206 with TLR3 polymorphisms exerts more than additive effects in Stevens-Johnson syndrome with severe ocular surface complications. PLoS One. doi：10.1371/journal.pone.0043650, 2012

polymorphism exerts additive effects in cold medicine-related Stevens-Johnson syndrome with severe ocular complications. Hum Genome Var. doi：10.1038/hgv.2015.23, 2015

26）Ueta M, Nishigaki H, Sotozono C et al：Downregulation of interferon-γ-induced protein 10 in the tears of patients with Stevens-Johnson syndrome with severe ocular complications in the chronic stage. BMJ Open Ophthalmol. doi：10.1136/bmjophth-2017-000073, 2017

27）Ueta M, Nishigaki H, Mizushima K et al：Regulation of innate immune response by miR-628-3p upregulated in the plasma of Stevens-Johnson syndrome patients. Ocul Surf 21：174-177, 2021