Identification of genetic polymorphisms in Stevens Johnson syndrome and toxic epidermal necrolysis

史蒂文斯约翰逊综合征和中毒性表皮坏死松解症遗传多态性的鉴定

• 批准号: 10609663
• 负责人: Hajirah Saeed
• 金额: $ 25.48万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10609663
• 关键词: Admission activity; Adverse reactions; Affect; Age; Alleles; American; Area; Asian ancestry; Biological; Blindness; Blood; Carbamazepine; Caucasians; Chronic; Cicatrix; Clinic; Clinical effectiveness; Code; Collaborations; Complication; Cornea; Cost of Illness; DNA; DNA Resequencing; Data; Data Collection; Data Set; Databases; Delayed Hypersensitivity; Department chair; Desiccation; Development; Development Plans; Disease; Drug Exposure; Drug Hypersensitivity; Ear; Environment; Ethnic Origin; Ethnic group; European; Exons; Eye; Fellowship; Foundations; Frequencies; Fright; Future; Gender; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic study; Genomics; Genotype; Growth; HLA-B Antigens; Haplotypes; Health Care Costs; Health Sciences; Healthcare Systems; Hong Kong; Incidence; Individual; Inflammation; Inpatients; Institutes; Institution; Large-Scale Sequencing; Lead; Length of Stay; Linkage Disequilibrium; Literature; Maps; Massachusetts; Medical; Mentors; Methods; Morbidity - disease rate; Multicenter Studies; Odds Ratio; Online Systems; Ophthalmology; Outcomes Research; Partner in relationship; Pathogenesis; Pathogenicity; Patients; Pharmaceutical Preparations; Population; Population Heterogeneity; Positioning Attribute; Prospective Studies; Public Health Schools; Quality of life; Rare Diseases; Reaction; Registries; Research; Research Design; Resources; Risk; Risk Factors; Saliva; Sample Size; Sampling; Scientist; Series; Signal Transduction; Site; Stevens-Johnson Syndrome; Survivors; System; T-Lymphocyte; Testing; Toxic Epidermal Necrolysis; Training; Trimethoprim-Sulfamethoxazole; United States; University Health Services; Urine; Variant; Work; base; biobank; care costs; career; career development; case control; cohort; comparative; cost; data standards; design; disability; disease natural history; disorder risk; electronic data; epidemiology study; exome; exome sequencing; genetic epidemiology; genetic risk factor; instructor; interest; medical schools; mortality; ocular surface; prevent; programs; rare variant; recruit; repository; research study; skills; tool

Candidate: Dr. Saeed is an Instructor in Ophthalmology at Massachusetts Eye and Ear Infirmary (MEEI), Harvard Medical School. She completed her cornea fellowship at MEEI in July 2016 and then took the intensive 7-week Program in Clinical Effectiveness at the Harvard School of Public Health (HSPH), meant to introduce quantitative and analytic research skills to medical professionals with an interest in pursuing a clinician-scientist career. Dr. Saeed's proposed career development plan includes pursuing an MPH degree with a concentration in Genetic Epidemiology and Statistical Genetics at HSPH. Her career development plan includes expanding her skills in three areas in order to study new aspects in Stevens Johnson Syndrome/toxic epidermal necrolysis (SJS/TEN): 1) quantitative methods for engaging in genetic epidemiology research, 2) outcomes research in rare diseases, including database development, 3) multi-center study design. Environment: Dr. Saeed's career development will be supported by a rich academic environment at Harvard institutions dedicated to her growth as a clinician-scientist. The Harvard system has one of the highest volumes of SJS/TEN patients per year in the nation. The extensive resources at MEEI and the Harvard system, including the Ocular Genomics Institute, represent an extraordinary environment to train and conduct the proposed research. Her mentors and collaborators include national experts in genetic epidemiology (Dr. Janey Wiggs and Dr. Daniel Chasman), SJS/TEN (Dr. James Chodosh and Dr. Elizabeth Phillips), and outcomes research and database development (Dr. Richard Gliklich). She has the full support of her department chair, Dr. Joan W. Miller. Research: SJS/TEN are on a spectrum of a rare mucocutaneous disease that most commonly manifest as an adverse reaction to a medication. Involvement of the ocular surface can lead to corneal blindness and 85% of survivors are thought to have chronic ocular disease. Data suggest that there are ethnicity and medication dependent genetic predispositions to developing SJS/TEN. Most studies have been done in genetically homogenous populations and with relatively small sample sizes. No studies have used whole exome sequencing to detect rare variants influencing pathogenesis of SJS/TEN. Dr. Saeed seeks to study the genetic predispositions to developing SJS/TEN through a multi-center collaboration. There is no national registry or biorepository of SJS/TEN patients. These will be essential in prospectively studying this rare and devastating disease, both through the proposed project and in future work on the genetics and immunopathogenesis of SJS/TEN. Her new collaborations with the Uniformed Services University of the Health Sciences will allow for large scale sequencing on various racial and drug cohorts and will allow her to detect genetic polymorphisms that may confer risk of SJS/TEN. Trimethoprim sulfamethoxazole (TS) is thought to be a common inciting agent of SJS/TEN in the US and will be studied in particular. Only one study in the literature has examined genetic risk factors in TS-induced SJS and it was purely an HLA genotyping study.

候选人：Saeed 博士是马萨诸塞州眼耳医院 (MEEI) 的眼科讲师， 哈佛医学院。她于 2016 年 7 月在 MEEI 完成了角膜研究金，然后参加了 哈佛大学公共卫生学院 (HSPH) 为期 7 周的强化临床有效性项目，旨在 向有兴趣追求医学专业人士介绍定量和分析研究技能 临床医生科学家的职业生涯。 Saeed 博士提出的职业发展计划包括攻读公共卫生硕士学位 HSPH 专注于遗传流行病学和统计遗传学。她的职业发展规划 包括扩展她在三个领域的技能，以便研究史蒂文斯约翰逊综合症/有毒物质的新方面 表皮坏死松解症（SJS/TEN）：1）从事遗传流行病学研究的定量方法，2） 罕见疾病的成果研究，包括数据库开发，3）多中心研究设计。 环境：赛义德博士的职业发展将得到哈佛大学丰富的学术环境的支持 致力于帮助她成长为临床医生科学家的机构。哈佛系统是拥有最高容量的系统之一 全国每年有 10 名 SJS 患者。 MEEI 和哈佛系统的丰富资源， 包括眼基因组研究所，为培训和开展 提出的研究。她的导师和合作者包括国家遗传流行病学专家（Janey博士） Wiggs 和 Daniel Chasman 博士）、SJS/TEN（James Chodosh 博士和 Elizabeth Phillips 博士）以及结果 研究和数据库开发（Richard Gliklich 博士）。她得到了系主任的全力支持， 琼·W·米勒博士。研究：SJS/TEN 属于一种罕见的皮肤粘膜疾病，大多数人都患有这种疾病 通常表现为对药物的不良反应。眼表受累可导致 角膜失明，85% 的幸存者被认为患有慢性眼病。数据表明，有 是发展 SJS/TEN 的种族和药物依赖性遗传倾向。大多数研究都有 是在遗传同质群体中以相对较小的样本量进行的。没有研究有 使用全外显子组测序来检测影响 SJS/TEN 发病机制的罕见变异。赛义德博士寻求 通过多中心合作研究发展 SJS/TEN 的遗传倾向。没有 SJS/TEN 患者的国家登记处或生物储存库。这些对于前瞻性研究这一点至关重要 罕见和毁灭性的疾病，无论是通过拟议的项目还是在未来的遗传学和 SJS/TEN 的免疫发病机制。她与制服服务健康大学的新合作 科学将允许对各种种族和药物群体进行大规模测序，并使她能够检测 可能带来 SJS/TEN 风险的基因多态性。甲氧苄啶磺胺甲恶唑 (TS) 被认为是 一种在美国常见的 SJS/TEN 煽动剂，将予以特别研究。仅有一项文献研究 已经检查了 TS 诱发的 SJS 的遗传危险因素，这纯粹是一项 HLA 基因分型研究。

项目成果

Long-Term Effect of a Treatment Protocol for Acute Ocular Involvement in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.

史蒂文斯-约翰逊综合征/中毒性表皮坏死松解症急性眼部受累治疗方案的长期效果。

• DOI: 10.1016/j.ajo.2019.07.006
• 发表时间: 2019-12
• 期刊: American journal of ophthalmology
• 影响因子: 4.2
• 作者: Shanbhag SS;Rashad R;Chodosh J;Saeed HN
• 通讯作者: Saeed HN

Acute and Chronic Management of Ocular Disease in Stevens Johnson Syndrome/Toxic Epidermal Necrolysis in the USA.

• DOI: 10.3389/fmed.2021.662897
• 发表时间: 2021
• 期刊: Frontiers in medicine
• 影响因子: 3.9
• 作者: Metcalfe D;Iqbal O;Chodosh J;Bouchard CS;Saeed HN
• 通讯作者: Saeed HN

The effects of systemic cyclosporine in acute Stevens-Johnson syndrome/toxic epidermal necrolysis on ocular disease.

• DOI: 10.1016/j.jtos.2020.05.003
• 发表时间: 2021-01
• 期刊: The ocular surface
• 作者: Hall LN;Shanbhag SS;Rashad R;Chodosh J;Saeed HN
• 通讯作者: Saeed HN

Acute ophthalmic manifestations in Mycoplasma induced rash and mucositis.

支原体引起的皮疹和粘膜炎的急性眼部表现。

• DOI: 10.1016/j.jtos.2022.03.004
• 发表时间: 2022
• 期刊: The ocular surface
• 作者: Rashad,Ramy;Elhusseiny,AbdelrahmanM;Shanbhag,SwapnaS;Chodosh,James;Saeed,HajirahN
• 通讯作者: Saeed,HajirahN

Long-term outcomes of amniotic membrane treatment in acute Stevens-Johnson syndrome/toxic epidermal necrolysis.

• DOI: 10.1016/j.jtos.2020.03.004
• 发表时间: 2020-07
• 期刊: The ocular surface
• 作者: Shanbhag SS;Hall L;Chodosh J;Saeed HN
• 通讯作者: Saeed HN