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）：重新担心天花病毒可能被用作生物恐怖主义代理，导致了有限的疫苗接种计划的早期实施。由于湿疹疫苗是疫苗疫苗的恐惧并发症，因此严格的标准排除了目前患有特应性皮炎（AD）或以前遭受过AD的人，甚至与AD的人接触AD的人。据估计，上述标准将至少将当前美国人口的至少50％排除在自愿免疫之外。但是，如果发生生物恐怖袭击，则无法保持这种排除标准，因为必须立即开始进行大规模疫苗接种以防止病毒进一步传播。该提案的目的是确定基于表皮屏障功能异常的免疫遗传标准（普遍的假设）（普遍的假设）或替代假设，AD的临床亚组有疫苗并发症的风险。 已经提出了两种病理生理机制来解释AD患者的倾向增加，以发展细菌和毒毒感染。一个假设假设AD是遗传免疫缺陷的外部表现，而我们怀疑它可能是皮肤的抗菌/渗透性障碍，主要解释了AD中的病毒性传播。这项研究将首先确定谁具有开发湿疹疫苗的最高风险，比较各种推定的AD临床亚组中的皮肤屏障功能测量和生化参数以确定渗透性屏障状态。在同一AD队列中，我们将同时评估异常Th2细胞功能的一组免疫遗传标记，包括IL -4，-5，-13，-18和IFN Gamma的改变。这些研究的结果将首先使用Alllow医生使用一种或两种方法来确定谁对湿疹疫苗的风险最高。其次，这些研究可能会允许医生预处理患有AD或相关疾病亚组但仍需要疫苗疫苗的患者，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患有AD或AD病史的人可以安全接收疫苗疫苗；并确定皮肤预处理是否会降低必须接受疫苗疫苗的高风险患者的湿疹疫苗的风险。这项研究的长期目标是确定表皮抗菌和渗透性屏障缺陷的相对贡献与AD患者开发传播病毒感染的免疫遗传异常相对于免疫遗传异常。

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

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.

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

Expression of epidermal CAMP changes in parallel with permeability barrier status.

• DOI: 10.1038/jid.2011.210
• 发表时间: 2011-11
• 期刊: JOURNAL OF INVESTIGATIVE DERMATOLOGY
• 影响因子: 6.5
• 作者: Rodriguez-Martin, Marina;Martin-Ezquerra, Gemma;Man, Mao-Qiang;Hupe, Melanie;Youm, Jong-Kyung;Mackenzie, Donald S.;Cho, Soyun;Trullas, Carles;Holleran, Walter M.;Radek, Katherine A.;Elias, Peter M.
• 通讯作者: Elias, Peter M.