Risk Factors for Eczema Vaccinatum in Atopic Dermatitis

特应性皮炎中发生疫苗性湿疹的危险因素

• 批准号: 7571642
• 负责人: WALTER M HOLLERAN
• 金额: $ 38.37万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-06 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7571642
• 关键词: Accounting; Affect; Aftercare; Age; Antiviral Agents; Atopic Dermatitis; Biochemical; Biochemical Markers; Biopsy; Biopsy Specimen; Bioterrorism; Blood; Catabolism; Cell physiology; Cells; Clinical; Complication; Cutaneous; Defect; Development; Disease; Drug Formulations; Eczema; Eczema Vaccinatum; Environment; Evaluation; Event; Exclusion Criteria; Exhibits; Fright; Functional disorder; Gender; Genes; Genetic Markers; Goals; Growth Factor; Hand; Immune; Immunization; Immunogenetics; Infection; Inflammatory; Inherited; Interferon Type II; Interleukin-13; Interleukin-18; Interleukin-4; Interleukin-5; Kinetics; Lipids; Mass Vaccinations; Measures; Mediating; Messenger RNA; Modeling; Mus; Patients; Permeability; Persons; Physicians; Population; Predisposition; Production; Psoriasis; Recording of previous events; Recovery; Relative (related person); Risk; Risk Factors; SCID Mice; Sampling; Site; Skin; Smallpox Viruses; Subgroup; Time; Vaccination; Vaccines; Vaccinia; Vaccinia Vaccine; Viral; Virus; Virus Diseases; Wild Type Mouse; animal care; antimicrobial; atopy; base; cohort; cytokine; high risk; inhibitor/antagonist; prevent; programs; repaired; restoration; skin disorder

DESCRIPTION (provided by applicant): Renewed concern that smallpox virus might be employed as a bioterrorism agent has led to an early implementation of a limited vaccination program. Because eczema vaccinatum is a feared complication of the Vaccinia vaccine, stringent criteria have excluded persons who currently suffer from atopic dermatitis (AD), or who have previously suffered from AD, and even close contacts of persons who have AD, from vaccination. The above criteria are estimated to exclude at least 50% of the current US population from voluntary immunization. In the event of a bioterrorism attack, however, such exclusion criteria could not be maintained, since mass vaccination would have to be initiated immediately to prevent further spread of the virus. The goal of this proposal is to identify which clinical subgroups of AD are at risk for Vaccinia complications, based upon either immunogenetic criteria (the prevailing hypothesis), or an alternate hypothesis, based upon abnormalities in epidermal barrier function. Two pathophysiologic mechanisms have been proposed to explain the increased propensity of persons with AD to develop bacterial and viiral infections. One hypothesis postulates that AD is an external manifestation of inherited immune defects, while alternatively we suspect that it could be the skin's antimicrobial/permeability barrier that primarily account for viral dissemination in AD. This study will first determine who is at the highest risk of developing eczema vaccinatum, comparing skin barrier functional measure-ments and biochemical parameters in various putative AD clinical subgroups to determine permeability barrier status. In the same AD cohorts, we will simultaneously assess a panel of immuno-genetic markers of abnormal TH2 cell function, including alterations in IL-4, -5, -13, -18, and IFN gamma. Results of these studies will first, alllow physicians to use the one or both approaches to determine who is at the highest risk for eczema vaccinatum. Second, these studies will potentially allow physicians to pretreat patients who have AD or related disease subgroups, but still require the Vaccinia vaccine, to decrease the risk in the eczema vaccinatum. In summary, the short-term goals of this study are to determine which persons suffering from AD or a history of AD can safely receive the Vaccinia vaccine; and to determine if skin pretreatment decreases the risk of eczema vaccinatum in patients at high risk who must receive the Vacciniia vaccine. The long-term goals of this study are to determine the relative contributions of epidermal antimicrobial and permeability barrier defects vs. immunogenetic abnormalities for the development of disseminated viral infections in patients with AD.

描述(由申请人提供)：对天花病毒可能被用作生物恐怖主义制剂的新一轮担忧导致了一项有限疫苗接种计划的早期实施。由于疫苗湿疹是疫苗的一种令人恐惧的并发症，严格的标准将目前患有特应性皮炎(AD)或以前患有AD的人，甚至是AD患者的密切接触者排除在接种疫苗之外。上述标准估计将至少50%的当前美国人口排除在自愿免疫之外。然而，如果发生生物恐怖主义袭击，这种排除标准将无法维持，因为必须立即开始大规模接种疫苗，以防止病毒的进一步传播。这项建议的目的是根据免疫遗传标准(主流假说)或基于表皮屏障功能异常的替代假说，确定AD的哪些临床亚组有发生痘苗并发症的风险。 已经提出了两种病理生理机制来解释阿尔茨海默病患者发生细菌和病毒感染的倾向增加。一种假设认为AD是遗传性免疫缺陷的外部表现，而另一种假设是，我们怀疑可能是皮肤的抗菌/渗透屏障导致了AD中的病毒传播。这项研究将首先确定谁是患湿疹疫苗的最高风险者，比较不同AD临床亚组的皮肤屏障功能测量和生化参数，以确定通透性屏障状态。在相同的AD队列中，我们将同时评估一组TH2细胞功能异常的免疫遗传标志物，包括IL-4、-5、-13、-18和干扰素-γ的变化。这些研究的结果将首先允许医生使用其中一种或两种方法来确定谁是湿疹疫苗感染的最高风险者。其次，这些研究可能允许医生对患有AD或相关疾病亚组的患者进行预治疗，但仍需要接种牛痘疫苗，以降低湿疹疫苗的风险。 总而言之，这项研究的短期目标是确定哪些阿尔茨海默病患者或有阿尔茨海默病病史的人可以安全地接种疫苗；以及确定皮肤预处理是否降低了必须接受疫苗接种的高危患者患湿疹疫苗的风险。这项研究的长期目标是确定表皮抗菌和通透性屏障缺陷与免疫遗传异常在AD患者播散性病毒感染发展中的相对贡献。

项目成果

Barrier requirements as the evolutionary "driver" of epidermal pigmentation in humans.

• DOI: 10.1002/ajhb.21043
• 发表时间: 2010-07
• 期刊: AMERICAN JOURNAL OF HUMAN BIOLOGY
• 影响因子: 2.9
• 作者: Elias, Peter M.;Menon, Gopinathan;Wetzel, Bruce K.;Williams, John (Jack) W.
• 通讯作者: Williams, John (Jack) W.

An Appropriate Response to the Black-Box Warning: Corrective, Barrier Repair Therapy in Atopic Dermatitis.

对黑盒警告的适当反应：特应性皮炎的纠正、屏障修复疗法。

• 发表时间: 2009
• 期刊: Clinical medicine. Dermatology
• 作者: Elias,PeterM

Psychological stress regulates antimicrobial peptide expression by both glucocorticoid and ýý-adrenergic mechanisms.

心理压力通过糖皮质激素和α-肾上腺素能机制调节抗菌肽的表达。

• DOI: 10.1684/ejd.2011.1273
• 发表时间: 2011
• 期刊: European journal of dermatology : EJD
• 作者: Martin-Ezquerra,Gemma;Man,Mao-Qiang;Hupe,Melanie;Rodriguez-Martin,Marina;Youm,Jong-Kyung;Trullas,Carles;Mackenzie,DonaldS;Radek,KatherineA;Holleran,WalterM;Elias,PeterM
• 通讯作者: Elias,PeterM

Filaggrin deficiency confers a paracellular barrier abnormality that reduces inflammatory thresholds to irritants and haptens.

• DOI: 10.1016/j.jaci.2009.06.046
• 发表时间: 2009-09
• 期刊: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
• 影响因子: 14.2
• 作者: Scharschmidt, Tiffany C.;Man, Mao-Qiang;Hatano, Yutaka;Crumrine, Debra;Gunathilake, Roshan;Sundberg, John P.;Silva, Kathleen A.;Mauro, Theodora M.;Hupe, Melanie;Cho, Soyun;Wu, Yan;Celli, Anna;Schmuth, Matthias;Feingold, Kenneth R.;Elias, Peter M.
• 通讯作者: Elias, Peter M.

Efficacy of combined peroxisome proliferator-activated receptor-α ligand and glucocorticoid therapy in a murine model of atopic dermatitis.

• DOI: 10.1038/jid.2011.144
• 发表时间: 2011-09
• 期刊: JOURNAL OF INVESTIGATIVE DERMATOLOGY
• 影响因子: 6.5
• 作者: Hatano, Yutaka;Elias, Peter M.;Crumrine, Debra;Feingold, Kenneth R.;Katagiri, Kazumoto;Fujiwara, Sakuhei
• 通讯作者: Fujiwara, Sakuhei