Risk of progression to autoimmune disease in severe drug eruption patients: identification of risk factors and trial for risk factor-guided stratification
| Project/Area Number |
19K08755
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53050:Dermatology-related
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| Research Institution | Kyorin University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
青山 裕美 川崎医科大学, 医学部, 教授 (90291393)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 薬剤性過敏症症候群 / 自己免疫疾患 / ウィルス再活性化 / 免疫再構築症候群 / risk factor / biomarker / regulatory T細胞 / バイオマーカー / 自己免疫性疾患 / リスクファクター |
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| Outline of Research at the Start |
薬剤性過敏症症候群(DiHS/DRESS)では様々なヘルペスウィルスが再活性化し、長い経過で自己免疫疾患が発症する. そのため、DiHS/DRESSはウィルス感染から自己免疫疾患発症までの免疫動態の推移を経時的に検討できる理想的な疾患モデルと言える.我々は今までの臨床研究から、自己免疫疾患の発症には様々な特徴が存在する可能性に気付いた. 本研究では、DiHS/DRESSの長期観察例を用いて自己免疫疾患発症のリスクファクターを確立することを目的とする. これにより自己免疫疾患発症の予測だけでなく、自己免疫疾患発症を防げるステロイドの使い方を明らかにし、長期予後の点からも最適な治療を確立したい.
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| Outline of Final Research Achievements |
The risk factors/biomarkers are key to uncover the etiology and pathogenesis of autoimmune disease. Drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is likely the best prototypic example for the analysis of events leading to autoimmune disease. The combination of increase in lymphocyte counts, severe liver damage, a rebound increase in globulin levels, long-lasting reactivations of Epstein-Barr virus and human herpesvirus 6, and low serum interleukin (IL)-2 and IL-4 levels at the acute/subacute phases, were significant biomarkers for the future development of autoimmune disease. We established a scoring system by which we could identify high-risk patients of autoimmune disease. Our data provide novel insights into autoimmune biology and represent the first scoring system that can identify patients at a high-risk of developing autoimmune disease.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の検討により、自己免疫疾患の発症をDIHS発症早期から予測しえることを明らかにしただけでなく、従来から言われてきた自己免疫疾患発症にはウィルスの再活性化が強く関与していることを明らかにすることができた。この結果は従来の明らかにされてこなかった自己免疫疾患の機序を明らかにするとともに、今後の重症薬疹の治療や経過観察にも大きな影響を与えうるものであり、その学術的社会的意義は大きいと考える。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Association of HLA-A*11:01 with sulfonamide-related severe cutaneous adverse reactions in Japanese patients.2020
Author(s)
Nakamura R, Ozeki T, Hirayama N, Sekine A, Yamashita T, Mashimo Y, Mizukawa Y, Shiohara T, Watanabe H, Sueki H, Ogawa K, Asada H, Kaniwa N, Tsukagoshi E, Matsunaga K, Niihara H, Yamaguchi Y, Aihara M, Mushiroda T, Saito Y, Morita E
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Journal Title
J Invest Dermatol
Volume: -
Issue: 8
Pages: 1659-1662
DOI
Related Report
Peer Reviewed
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[Journal Article] The nationwide epidemiological survey of Stevens-Johnson syndrome and toxic epidermal necrolysis in Japan, 2016-2018.2020
Author(s)
Sunaga Y, Kurosawa M, Ochiai H, Watanabe H, Sueki H, Azukizawa H, Asada H, Watanabe Y, Yamaguchi Y, Aihara M, Mizukawa Y, Ohyama M, Hama N, Abe R, Hashizume H, Nakajima S, Nomura T, Kabashima K, Tohyama M, Takahashi H, Mieno H, Ueta M, Sotozono C, Niihara H, Morita E, Kokaze A.
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Journal Title
J Dermatol Sci.
Volume: 100(3)
Issue: 3
Pages: 175-182
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] HLA-B*51:01 and CYP2C9*3 Are Risk Factors for Phenytoin-Induced Eruption in the Japanese Population: Analysis of Data From the Biobank Japan Project.2020
Author(s)
Hikino K, Ozeki T, Koido M, Terao C, Kamatani Y, Mizukawa Y, Shiohara T, Tohyama M, Azukizawa H, Aihara M, Nihara H, Morita E, Murakami Y, Kubo M, Mushiroda T
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Journal Title
Clin Pharmacol Ther
Volume: 107
Issue: 5
Pages: 1170-1178
DOI
Related Report
Peer Reviewed
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[Journal Article] Confusion in determination of two types of cutaneous adverse reactions to drugs, maculopapular eruption and erythema multiforme, among the experts: A proposal of standardized terminology2020
Author(s)
Hashizume H, Abe R, Azukizawa H, Fujiyama T, Hama N, Mizukawa Y, Morita E, Nakagawa Y, Nakajima S, Niihara H, Teraki Y, Tohyama M, Watanabe H, Tokura Y, Drug Allergy Database Committee in Japanese Cutaneous Immunology and Allergy Association
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Journal Title
J Dermatol
Volume: 47
Issue: 2
Pages: 169-173
DOI
Related Report
Peer Reviewed
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[Journal Article] Galectin-7 as a potential biomarker of Stevens-Johnson syndrome/ toxic epidermal necrolysis: Identification by targeted proteomics using causative drug-exposed peripheral blood cells2019
Author(s)
Natsumi Hama, Keiko Nishimura, Akito Hasegawa, Akihiko Yuki, Hideaki Kume, Jun Adachi, Manao Kinoshita, Youichi Ogawa, Saeko Nakajima, Takashi Nomura, Hideaki Watanabe, Yoshiko Mizukawa, Takeshi Tomonaga, Hiroshi Shimizu, Riichiro Abe
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Journal Title
J Allergy Clin Immunol Pract
Volume: 印刷中
Issue: 8
Pages: 2894-2897
DOI
Related Report
Peer Reviewed
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