African-Americans with Atopic Dermatitis: Skin Barrier and Immune

患有特应性皮炎的非裔美国人：皮肤屏障和免疫

• 批准号: 9868281
• 负责人: David Margolis
• 金额: $ 34.43万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-18 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9868281
• 关键词: Adult; Affect; African; African American; Age-Months; Allergens; Asians; Asthma; Atopic Dermatitis; Biocompatible Materials; Biology; Child; Childhood; Chronic; Chronic Disease; Code; Development; Disease; Eczema; Ethnic group; European; Filament; Frequencies; Functional disorder; Genes; Genetic; Genetic Epistasis; Genetic Variation; Goals; High Prevalence; Immune; Immune system; Individual; Inflammatory; Knowledge; Longitudinal cohort; Lupus; Mental Depression; Mental disorders; Modeling; Mutation; Non-Malignant; Pathway interactions; Phenotype; Population; Prevalence; Production; Productivity; Prognosis; Proteins; Pruritus; Public Health; Publishing; Quality of life; Race; Recurrence; Registries; Relapse; Reporting; Risk; Role; Schools; Science; Sleep disturbances; Stimulus; Structure; TSLP gene; Variant; Work; base; burden of illness; cohort; disability; early childhood; filaggrin; immunoregulation; infection risk; loss of function; loss of function mutation; novel; protein aggregation; protein function; psychological distress; public health relevance; seasonal allergies; skin barrier; skin disorder; social; targeted treatment

 DESCRIPTION (provided by applicant): Atopic dermatitis (AD) is a highly pruritic chronic episodic inflammatory skin disease that often presents between 3 and 6 months of age but may also present during later childhood or in adulthood. In the US, AD affects roughly 10-20% of all children of all races and ethnic groups. The highest prevalence of AD in the US is among African-Americans. The prevalence of AD is increasing worldwide and it is a major public health burden. The majority of children with AD will also develop asthma and seasonal allergies. From the recent Global Burden of Disease study, AD was among the top 50 most prevalent diseases worldwide and it had the second highest disability rank of all non-malignant skin diseases. Recent studies have established a strong association between loss-of-function mutations in filaggrin (FLG), a gene coding for a protein responsible for maintaining an intact skin barrier and AD. We have already demonstrated that these mutations are also associated with more persistent AD. However, these mutations are rarely noted in children of African ancestry. As a result, there is a gap in our knowledge with respect to the basic biology of AD in African-Americans. We recently found that mutations in filaggrin-2 (FLG2) are associated with persistence of AD in African-American children. We have also shown that genetic variation of the gene that codes thymic stromal lymphopoietin appears to modify the association of FLG with AD. The goals of this proposal are to comprehensively explore the association of FLG2 with AD in African-Americans, to better understand the association of thymic stromal lymphopoietin with the persistence of AD, and to explore how TSLP/FLG2 interact to create the phenotype of persistent AD. We will continue to focus on loss-of- function mutations in skin barrier genes using FLG as a model, a concept that was recently justified by a report that LOF may be a preferred pathway for adaptation to environmental stimuli. We plan to focus our studies on African-Americans. This proposal has two goals. The first goal is to better understand FLG2 loss-of-function mutations in African Americans. The second goal is to better understand TSLP variation and ultimately the interaction between TSLP and barrier dysfunction.



项目成果

Identification of HLA-DPA1*01:03:01:57 and HLA-DPA1*02:01:01:29 from a case-control study of atopic dermatitis.

从特应性皮炎病例对照研究中鉴定 HLA-DPA1*01:03:01:57 和 HLA-DPA1*02:01:01:29。

• DOI: 10.1111/tan.14900
• 发表时间: 2023
• 期刊: HLA
• 影响因子: 8
• 作者: Damianos,Georgios;Duke,JamieL;Pagkrati,Ioanna;Margolis,DavidJ;Monos,DimitriS
• 通讯作者: Monos,DimitriS

Uncommon variants in FLG2 and TCHHL1 are associated with remission of atopic dermatitis in a large longitudinal US cohort.

• DOI: 10.1007/s00403-021-02319-7
• 发表时间: 2022-12
• 期刊: Archives of dermatological research
• 影响因子: 3

Human leukocyte antigen class-I variation is associated with atopic dermatitis: A case-control study.

• DOI: 10.1016/j.humimm.2021.04.001
• 发表时间: 2021-08
• 期刊: Human immunology
• 影响因子: 2.7
• 作者: Margolis DJ;Mitra N;Duke JL;Berna R;Margolis JD;Hoffstad O;Kim BS;Yan AC;Zaenglein AL;Chiesa Fuxench Z;Dinou A;Wasserman J;Tairis N;Mosbruger TL;Ferriola D;Damianos G;Kotsopoulou I;Monos DS
• 通讯作者: Monos DS

HLA Class I Polymorphisms Influencing Both Peptide Binding and KIR Interactions Are Associated with Remission among Children with Atopic Dermatitis: A Longitudinal Study.

• DOI: 10.4049/jimmunol.2001252
• 发表时间: 2021-05-01
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Margolis DJ;Mitra N;Kim BS;Duke JL;Berna RA;Hoffstad OJ;Wasserman JR;Ferriola DA;Mosbruger TL;Wubbenhorst BS;Nathanson KL;Monos DS
• 通讯作者: Monos DS