MicroRNA analysis of childhood atopic dermatitis reveals a role for miR‐451a*

Abstract

Summary Background MicroRNAs (miRNAs), important regulators of gene expression, have been implicated in a variety of disorders. The expression pattern of miRNAs in paediatric atopic dermatitis (AD) has not been well studied. Objectives We sought to investigate miRNA expression profiles in different blood compartments of infants with AD. Methods Small RNA and analysis with the HTG EdgeSeq system were performed to identify differentially expressed miRNAs in peripheral blood mononuclear cells (PBMCs) and plasma of infants with AD vs. age‐matched healthy controls, with reverse transcription quantitative real‐time polymerase chain reaction (RT‐qPCR) used for validation and measurement of miRNA targets. Logistic regression models with area under the receiving operating characteristic estimation was used to evaluate the diagnostic potential of chosen miRNAs for AD. Results RNA sequencing was performed to access miRNA expression profiles in paediatric AD. We identified 10 differentially expressed miRNAs in PBMCs and eight dysregulated miRNAs in plasma of infants with AD compared with controls. Upregulated miRNAs in PBMCs included miRNAs known to be involved in inflammation: miR‐223‐3p, miR‐126‐5p and miR‐143‐3p. Differential expression of only one miRNA, miR‐451a, was observed in both PBMCs and plasma of children with AD. Dysregulation of three miRNAs (miR‐451a, miR‐143‐3p and miR‐223‐3p) was validated in larger numbers of samples and miR‐451a was identified as a predictive biomarker for the early diagnosis of the disease. Experimentally verified targets of miR‐451a, interleukin 6 receptor (IL6R) and proteasome subunit beta type‐8 (PSMB8), were increased in patients with AD, negatively correlated with miR‐451a levels and upregulated following inhibition of miR‐451a in PBMCs. Conclusions In infants with AD, a distinct peripheral blood miRNA signature is seen, highlighting the systemic effects of the disease. miR‐451a is uniquely expressed in different blood compartments of patients with AD and may serve as a promising novel biomarker for the early diagnosis of AD.

Classifying atopic dermatitis: a systematic review of phenotypes and associated characteristics

“…Regarding WHO region, the majority of studies were conducted in the European Region ( n = 50, 55%), followed by the Western Pacific Region ( n = 21, 23%), the Region of the Americas ( n = 16, 18%) and the African Region and the Eastern Mediterranean Region (both n = 1, 1%). Investigated characteristics included the following categories: skin barrier function ( n = 15), 19–33 serum blood cell types and markers ( n = 23), 9,18,23,34–53 serum Ig levels and sensitization ( n = 15), 20,22,25,51,54–64 microbial colonization ( n = 10), 15,65–73 DNA mutations ( n = 14), 10,51,74–85 skin parameters ( n = 8), 32,86–92 personal and family history of allergy ( n = 4), 58,93–95 comorbidities ( n = 7), 8,51,96–100 morphology ( n = 3) 51,93,101 and other characteristics ( n = 5) 51,95,102–104 (see Table a and Appendix , Supporting Information).…”

“…Regarding WHO region, the majority of studies were conducted in the European Region (n = 50, 55%), followed by the Western Pacific Region (n = 21, 23%), the Region of the Americas (n = 16, 18%) and the African Region and the Eastern Mediterranean Region (both n = 1, 1%). Investigated characteristics included the following categories: skin barrier function (n = 15), [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] serum blood cell types and markers (n = 23), 9,18,23,[34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] serum Ig levels and sensitization (n = 15), 20,22,25,51,54-64 microbial colonization (n = 10), 15,[65][66][67][68][69][70][71][72][73] DNA mutations (n = 14), 10,51,…”

“…25,59,79 In addition, in many articles, no further specification of the basis of the severity definition was given. 10,15,38,42,44,68,69,89,52,91 Phenotypes based on disease trajectories (phenotype group 2) Within this phenotype category, 50% (28/56) of studies was cross-sectional, 57% (32/56) was hospital-based only, and in 18% (10/56), a data-driven approach was used. In the studies, the number of included AD patients ranged from nine to 108 703.…”

Early life regulation of inflammation in atopic dermatitis by microRNA

“…Early life regulation of inflammation in atopic dermatitis by microRNA DOI: 10.1111/bjd.19475 In this issue of the BJD, Nousbeck et al explore the expression of microRNAs (miRNAs) in different blood compartments, and postulate their use as noninvasive biomarkers for paediatric eczema. 1 miRNAs are groups of short (21-24 nucleotides) noncoding RNA molecules, controlling gene expression at the post-transcriptional level. 2 Even though they are never translated to protein themselves, miRNAs critically regulate key biological processes, including cell cycle progression and death, differentiation, maturation and activation of immune cells.…”

“…In this issue of the BJD , Nousbeck et al . explore the expression of microRNAs (miRNAs) in different blood compartments, and postulate their use as noninvasive biomarkers for paediatric eczema 1 …”