Humoral and Cellular Immune Responses in Hen's Egg Oral Immunotherapy
试验速览
- 阶段
- 不适用
- 入组人数
- 50
- 主要终点
- OIT-induced allergen-specific antibody responses
研究概览
简要总结
The study determines how a 6 months oral immunotherapy (OIT) program with hen's egg (HE) effects cellular and humoral immune responses in 50 children with HE allergy. Clinical data, transcriptomics and epigenetics are combined and analyzed by advanced system biology methods. This study will provide better understanding of the effects and mechanisms of OIT.
详细描述
Oral immunotherapy (OIT) is a therapeutic approach, where gradually increasing doses of a specific food allergen are administered orally. OIT can desensitize up to 80% of children with persistent food allergy, and in a subset lead to sustained immune tolerance. The immunologic mechanisms induced by OIT are still poorly understood.
In this randomized cross-over study, 50 children with challenge-confirmed hen's egg (HE) allergy will be randomized (2:1) to receive either active HE OIT or continue on an avoidance diet for 6 months after which active OIT is started. The immunological changes induced by OIT will be compared to the patient's initial status and to that of the patients on an avoidance diet.
Serum antibody and humoral mediator analyses as well as gene expression of blood mononuclear cell (PBMC) by genome-wide microarray assays will be studied. PBMCs will be stimulated with HE allergens and innate immunity agonists, and the differences in the expression profiles of messenger-RNAs as well as microRNAs will be studied. Single-cell sequencing and sorting of regulator T cells (Tregs) will be performed focusing on their transcriptomic responses and gene methylation. Finally, clinical data, transcriptomics and epigenetic changes will be combined and analyzed by advanced system biology methods.
This study will provide better understanding of the effects and mechanisms of OIT and identify biomarkers for selection of patients benefitting from personalized OIT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 19 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 6-19 years
- •Sensitization to egg white (egg white- specific IgE ≥0.35 kU/l or skin prick test ≥3 mm)
- •Positive double-blind, placebo-controlled food challenge to heated egg white
排除标准
- •Poor adherence
- •Uncontrolled or severe asthma
- •Severe systemic illness
- •Active autoimmune disease
- •Active, malignant neoplasia
研究组 & 干预措施
Hen's egg OIT
Daily intake of gradually increasing doses of egg white protein under a 32 weeks period, continued by regular, daily intake of 1000 mg egg white protein.
干预措施: Hen's egg OIT (Dietary Supplement)
Hen's egg avoidance
Hen's egg is avoidance diet is continued.
结局指标
主要结局
OIT-induced allergen-specific antibody responses
时间窗: Up to 32 weeks
The amount of specific serum IgE, IgG4, and IgA antibodies (kU/L) to the major egg allergens (Gal d1 - d4) will be measured by ImmunoCAP after 0, 14, and 32 weeks of OIT or avoidance.
OIT-induced changes in the peripheral blood cell transcriptome
时间窗: Up to 32 weeks
Gene expression of blood mononuclear cells (PBMC) after 0, 14 and 32 weeks of OIT or avoidance will be studied. Total-RNA extracted from PBMCs will be used for microarrays. The genome-wide expression of the approximately 25.000 genes will be investigated on Agilent SurePrint G3 Human Gene Expression v3 arrays.
OIT-induced allergen-specific expression profiles of messenger-RNAs and microRNAs
时间窗: Up to 32 weeks
Comprehensive highthroughput sequencing for long (mRNA) and short (miRNA) coding gene expression approach will be used to investigate transcriptional changes in exposed blood cells after different stimulations (egg extract, LPS, PolyI:C)
次要结局
- The prorportion of participants able to consume 1000mg of egg protein after 32 weeks of OIT(Up to 32 weeks)
研究者
Kati Palosuo
MD, PhD, Principal investigator
Helsinki University Central Hospital