Stratum corneum markers of innate and T helper cell‐related immunity and their relation to the disease severity in Croatian patients with atopic dermatitis

Abstract

Background Atopic dermatitis (AD) presents with the wide spectrum of clinical phenotypes within and between various populations. Recent study showed low frequency of filaggrin loss-of-function (FLG LOF) mutations in Croatian AD patients. At present, there are no data on biomarkers of immune response in Croatian AD patients that might be useful in the selection and monitoring of novel immune therapies. Objectives To investigate levels of cytokines of various signature in the stratum corneum (SC) collected from lesional and non-lesional skin of AD patients and healthy controls and to evaluate their relationship with the severity of disease and skin barrier function.Methods SC samples were collected from 100 adult patients with moderate-to-severe AD and 50 healthy controls. The levels of 21 cytokines were measured by multiplex immunoassay. We conducted machine learning analysis to assess whether a small number of cytokine measurements can discriminate between healthy controls and AD patients and can predict AD severity (SCORAD). ResultsThe SC levels of thirteen cytokines representing innate immunity, Th-1, Th-2 and Th-17/22 immune response showed significant differences between healthy and AD skin. Our analysis demonstrated that as few as three cytokines measured in lesional skin can discriminate healthy controls and AD with an accuracy of 99% and that the predictive models for SCORAD did not achieve a high accuracy. Cytokine levels were highly correlated with the levels of filaggrin degradation products and skin barrier function.Conclusions Stratum corneum analysis revealed aberrant levels of cytokines representing innate immunity, Th-1-, Th-2-and Th-17/22-mediated immune response in Croatian AD patients. Increased Th-2 cytokines and their strong association with natural moisturizing factor (NMF) can explain low NMF levels despite of low frequency of FLG LOF mutations in Croatian population. Predictive models for SCORAD identified cytokines associated with SCORAD but warrants further investigation.

Factors associated with severity of atopic dermatitis – a Finnish cross‐sectional study

“…Factors that have been associated with severity are early onset, profound Th2‐immune shift, high serum IgE‐levels and eosinophil counts, concomitant asthma and known history of severe AD in first‐degree relatives 11,12 . There have also been studies on predictive biomarkers, filaggrin mutations (FLG) and polygenic prediction regarding severity, but results have been inconsistent 13–17 …”

“…11 , 12 There have also been studies on predictive biomarkers, filaggrin mutations (FLG) and polygenic prediction regarding severity, but results have been inconsistent. 13 , 14 , 15 , 16 , 17 …”

Epidermal biomarkers of the skin barrier in atopic and contact dermatitis

“…30 Furthermore, several studies have reported a strong association between NMF levels, TEWL and immunological biomarkers, underscoring the connection between the skin barrier and immune response. 31 NMF has been measured in clinical studies to monitor therapy, 32,33 the onset of disease 15,16 or to identify distinct disease endotypes. 34 A recent study by Ni Chaoimh et al revealed that measuring NMF levels in neonates within 4 days after birth can serve as a predictive biomarker for the FLG genotype.…”

Skin Microbiota in Atopic Dermatitis

“…Acute lesions are manifested as bright erythema, oedema and oozing, while chronic lesions present as xerosis, lichenification and residual dyspigmentation. In comparison to healthy controls, both non-lesional and lesional AD skin show higher transepidermal water loss (TEWL) and pH values [ 19 ] that corelate with disease severity and predisposition [ 20 , 21 ]. Distributional and morphological characteristics generally relate to age, whilst some phenotypes show predisposition for certain body sites.…”

“…Skin lipids (e.g., ceramides, free fatty acids and cholesterol) are vital for the maintenance of the epidermal barrier function, and thus are responsible for prevention of TEWL and penetration of irritants, allergens and microbes. Disbalance in the composition of skin lipids, as well as the reduction of the lipid content, are associated with the development of AD [ 19 , 42 ].…”