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.
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)
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
Single group
Development of atopic dermatitis with/without IgE autoantibodies
Other interventionNo 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 identified in cord blood, this may originate from the mother and passes to the child due to maternal spillover , or it is produced by the fetus (prenatally) who produces IgE autoantibodies him/herself or by the infant in early life. This project aims to insights to the understanding of the first stages of IgE autoantibody development, its relation to AD and other allergic diseases as well as heredity and environmental factors. The endpoints study hold the potential to improve prevention and/or prognosis.
Prevalence of IgE autoantibodies against skin epitopes in newborns
The prevalence (or first developmental stages) of IgE autoantibodies directed against keratinocyte-derived proteins in newborns (with high risk of atopic dermatitis).
Correlation between the presence of IgE autoantibodies and the development of atopic dermatitis
The presence of IgE autoantibodies will be measured after birth, at 6, 12 and 24 months of age. The skin will be examined by a dermatologist (resident) after birth, 6, 12 and 24 months for dryness and/or the presence of atopic dermatitis (according to the Hanifin and Rajka criteria). The subjects will be subdivided based on the presence of IgE autoantibodies and correlated with the skin conditions.
Correlation of IgE autoantibodies with IgE levels in serum
We will sub-divide the participants based on the presence of IgE autoantibodies (positive or negative) and analyse the levels of IgE in serum (kU/L).
Investigation of the hereditary factor in case IgE autoantibodies present
Serum is collected from both of the biological parents (if available/possible) to measure the presence of IgE autoantibodies for evaluatation of evaluation of the hereditary factor. 1. In case IgE autoantibodies are present in the infant after birth, we will evaluate if the mother is positive too (spill-over from the mother?). 2. If they develop autoantibodies during the two-year follow-up period, we will analyse if (one or both) the parents are positive as well.
Characterization of leukocytes in infants
1. Characterization of leukocytes in infants and correlate with the presence of IgE autoantibodies (positive, negative) 2. Characterization of leukocytes in infants and correlate with the development of AD (present yes/no)
Determination of serum inflammatory mediators
Inflammatory cytokines and chemokines in serum will be measured using the Luminex multiplex assay. Serum samples are collected at birth, 6, 12 and 24 months of age. The results can be linked to the presence/disease severity of atopic dermatitis (if present), IgE autoantibodies or other environmental factors (infection).
Skin barrier function: Electrical impedance spectroscopy
We will analyze the electrical impedance spectroscopy (EIS) using the Nevisense device (SciBase, Sweden) for the non-invasive objective measurement of the skin barrier function. Measurements are performed 1-3 days after birth (visit 2), at 6 (visit 3) and 24 months (visit 5) of age. The results will be linked to the development of atopic dermatitis, and if possible, to the presence of IgE autoantibodies and/or the skin microbiome.
Skin barrier function: Natural moisturizing factor
The natural moisturizing factor (NMF) consists of a group of components that exist in normal skin to maintain its function and hydration, including amino acids, lactic acid, pyrrolidone carboxylic acid, sugars, minerals, and peptides. Low levels of NMF have been correlated with a loss of function mutation in the filaggrin (FLG) gene. We measure the NMF levels at 6, 12 or 24 months of age using the prototype NMFScan (RiverD, The Netherlands) and the results will be linked to the development of atopic dermatitis, and if possible, the presence of IgE autoantibodies and/or skin microbiome.
Iron deficiency: Is there a link with atopic dermatitis and/or IgE autoantibodies?
Serum ferritin is the most reliable indicator of iron stores and used as the primary test for iron deficiency diagnosis. Low levels (\<30 μg/L in adults) indicate iron deficiency, while high levels can be present in inflammation or infection. The results will be linked to the presence of atopic dermatitis and/or IgE autoantibodies, but also to the data of the questionnaires.
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Universitair Ziekenhuis Brussel
Lead sponsor
Vrije Universiteit Brussel
Collaborator
