Birth Cohort: Development of IgE Autoantibodies in Newborns With (High Risk of) Atopic Dermatitis

Официальное название

Development of IgE Autoantibodies in Newborns With Atopic Dermatitis (DIANA) Birth Cohort

Обзор

Previous research has shown that some patients with atopic eczema have specific self-reactive antibodies, known as IgE autoantibodies, that react to their own skin cells, referred to as "self-reactive antibodies" or "autoantibodies". It is not yet known when and how these self-reactive antibodies develop, so this is what we aim to investigate. This study aims to examine the presence of self-reactive antibodies at birth. In other words, the investigators want to study the earliest stage of developing antibodies that target the body's own skin cells. Additionally, factors that contribute to the development of these self-reactive antibodies will be explored as well as the correlation with the development of atopic eczema. The study will involve newborns who are at an increased risk of developing atopic eczema due to a family history of asthma, hay fever, or atopic eczema. There will also be a control group of newborns without these characteristics. The study's approach is to examine a portion of the umbilical cord blood, which is routinely collected after birth, to investigate self-reactive antibodies. The goal is to determine whether these self-reactive antibodies are linked to the development of atopic eczema in the first two years of life. For this purpose, follow-ups will be conducted at the ages of 6, 12, and 24 months. This study will contribute to an increased understanding of the prevalence of self-reactive antibodies and the factors influencing their development. Moreover, the study will determine whether these antibodies play a role in the prevention of and/or serve as predictive factors for the development of atopic eczema.

Подробное описание

IgE autoantibodies against self-peptides in the skin have been identified in a subgroup of patients AD. These autoantibodies are present in subjects with comorbid allergic diseases in particular and are usually absent in healthy individuals, suggesting a link between IgE autoreactivity and allergic disease burden (Kortekaas Krohn I, et al. Allergy 2023). A prevalence of 15% of IgE autoantibodies was reported in infants younger than one year with AD, proving the development of IgE autoantibodies already early in life (Mothes N, et al. J Allergy Clin Immunol 2005).

The Development of IgE Autoantibodies in Newborns with (a high-risk of) Atopic dermatitis (DIANA) study is a large birth cohort, including a well-characterized and demographically diverse population with extensive early-life data of the infants and their parents. The DIANA birth cohort has an interdisciplinary design with a follow-up until the age of two years, enabling detailed monitoring of AD and other conditions.

In the present study, it is hypothesized that hereditary factors, lifestyle, and the environment can influence the development of self-reactive antibodies. To assess hereditary factors, a one-time blood sample will be taken from the biological mother and father, focusing solely on self-reactive antibodies and inflammatory substances. In addition, non-invasive and painless skin barrier measurements will be performed to study the skin barrier function. Environmental factors are investigated through questionnaires and swabs are being taken from the skin or stool to study the composition of the microbes.

The primary objective is:

To determine the presence of self-reactive antibodies at birth or early development.

Secondary objectives are:

1. to investigate whether the presence of self-reactive antibodies is correlated with the development of atopic eczema during the first two years of life 2. to study whether heredity can influence the development of self-reactive antibodies 3. to examine whether environmental factors can influence the development of self-reactive antibodies

Eligible parents who plan to give birth at the University Hospital (UZ) Brussel will be offered the opportunity to participate in the study. If they are interested, the prenatal baseline visit (visit 1) is scheduled. A total of five visits will be scheduled over two years. After birth, umbilical cord blood will be collected and the second visit will take place within 72 hours. Follow-up visits will be scheduled at 6 months of age (visit 3), 12 months (visit 4), and 24 months (visit 4).

Вмешательства

• Другое Development of atopic dermatitis with/without IgE autoantibodies
  No studies have been performed on the presence of IgE autoantibodies at birth and whether this is related to AD development, prediction of the development of atopic diseases (biomarker) or clinical relevance in the pathophysiology. Causative environmental and hereditary factors still need to be unraveled. We assume that newborns with IgE autoantibodies are prone to develop atopic dermatitis and its comorbidities (food allergy, allergic asthma/ rhinitis) . In case IgE autoantibodies are identifie

Первичные конечные точки

• Prevalence of IgE autoantibodies against skin epitopes in newborns [Срок оценки: From enrollment to study visit 2 after birth.]

Вторичные конечные точки (4)

• Correlation between the presence of IgE autoantibodies and the development of atopic dermatitis [Срок оценки: From visit 2 (after birth) to visit 5 at 24 months of age.]
• Correlation of IgE autoantibodies with IgE levels in serum [Срок оценки: From visit 2 after birth to visit 5 at 24 months of age.]
• Investigation of the hereditary factor in case IgE autoantibodies present [Срок оценки: From enrollment to visit 5 at 24 months.]
• Characterization of leukocytes in infants [Срок оценки: Through study completion, an average of 2 years]

Критерии участия

Критерии включения

Newborns who are planned to be born at the maternity ward of UZ Brussel with the following criteria:

• 400 newborns with high-risk for AD-development (at least 1 parent or sibling with physician diagnosed atopic dermatitis AND/OR asthma AND/OR allergic rhinitis)
• 100 newborns with low-risk for AD-development (no parents or siblings with history of atopic dermatitis AND/OR asthma AND/OR allergic rhinitis)

Критерии исключения

• Newborns not born at the maternity ward of UZ Brussel
• Parents with a poor understanding of Dutch, French or English
• Newborns who are admitted post-partum to the neonatal intensive care unit (gestational age <34 weeks) or with medical complications
• Newborns with severe genetic abnormalities/birth defects
• Newborns whose parents will not be able to attend the study visits for a period of 2 years (location, working hours)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

Бельгия · 1 центр

• Universitair Ziekenhuis (UZ) Brussel, Vrije Universiteit Brussel (VUB) — Jette

Публикации

• Charles N, Kortekaas-Krohn I, Kocaturk E, Scheffel J, Altrichter S, Steinert C, Xiang YK, Gutermuth J, Reber LL, Maurer M. Autoreactive IgE: Pathogenic role and therapeutic target in autoimmune diseases. Allergy. 2023 Dec;78(12):3118-3135. doi: 10.1111/all.15843. Epub 2023 Aug 9. PMID 37555488
• Kolkhir P, Altrichter S, Badloe FMS, Belasri H, Charles N, De Vriese S, Gutermuth J, Huygen L, Kocaturk E, Kortekaas Krohn I, Munoz M, Monino-Romero S, Reber LL, Scheffel J, Steinert C, Xiang YK, Maurer M. The European Network for IgE-Mediated Autoimmunity and Autoallergy (ENIGMA) initiative. Nat Med. 2024 Apr;30(4):920-922. doi: 10.1038/s41591-024-02819-9. No abstract available. PMID 38429523
• Kortekaas Krohn I, Badloe FMS, Herrmann N, Maintz L, De Vriese S, Ring J; CK-CARE Study Group; Bieber T, Gutermuth J. Immunoglobulin E autoantibodies in atopic dermatitis associate with Type-2 comorbidities and the atopic march. Allergy. 2023 Dec;78(12):3178-3192. doi: 10.1111/all.15822. Epub 2023 Jul 24. PMID 37489049
• Belasri H, De Leye H, Saerens J, Vandermeersch L, Badloe FM, Vandeneynde A, Lenie S, De Vriese S, Gies I, Cools F, Gucciardo L, Kortekaas Krohn I, Gutermuth J. Development of IgE autoantibodies in newborns with atopic dermatitis (DIANA): protocol of a prospective, non-interventional, observational birth cohort. BMJ Open. 2026 May 29;16(5):e114509. doi: 10.1136/bmjopen-2025-114509. PMID 42215271

Идентификаторы

NCT: NCT07316465 · EC-2023-074 · 18E2K24N · G056322N

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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