Dynamics of the chemokine ENA-78/CXCL5 levels in blood serum and skin exudate in patients with atopic dermatitis

Currently, there are only scarce data on dynamics of biologically active substances in the lesions associated with atopic dermatitis. Persistence of microorganisms in atopic dermatitis is high on the skin surface. However, pathophysiological significance of ENA-78/CXCL5 for development of atopic dermatitis was not studied so far. The ENA-78/CXCL5 is known to be produced by endotheliocytes, keratinocytes, eosinophils, fibroblasts to activate neutrophil migration, especially under the influence of LPS-containing microorganisms. The aim of this study was to evaluate the dynamics of ENA-78/CXCL5 chemokine levels in blood serum and skin exudates in the patients with atopic dermatitis, as well as to determine pathophysiological role of the chemokine in pathogenesis of dermatosis. 80 patients with limited and widespread forms of atopic dermatitis and 15 volunteers were under observation. The dynamics of ENA-78/CXCL5 levels was studied in blood sera and skin exudates. Blood samples for the study were drawn at the time periods of exacerbation and remission. Skin exudates were taken from the patients during the exacerbation period using disposable insulin syringes and 20-G disposable needles. In healthy volunteers, the skin exudate was obtained by the “skin window” technique as described by V.V. Klimov and coauthors “A method for assessing minimal inflammatory activity of skin in atopic dermatitis in remission”. The cell analysis was conducted by flow cytofluorimetry using the LEGEND plex TM Human Proinflammatory Chemokine Panel (USA) according to the manufacturer’s protocol. Serum concentrations of chemokine ENA-78/CXCL5 in adolescents with atopic dermatitis, exceeded the range for healthy volunteers. During remission of dermatitis, the chemokine level did not reach the indices in the control group. In adults, the ENA-78/CXCL5 concentration, both at the onset of symptoms and upon their resolution, was below the control levels. Maximal concentrations of ENA-78/CXCL5 chemokine were detected in the skin exudates. As based on our data on the dynamics of ENA-78/CXCL5 chemokine levels, it could be assumed that this substance may represent a sufficient link in pathogenesis of atopic dermatitis, by causing migration of neutrophils and monocytes to the affected area. The ENA-78/CXCL5 chemokine may be a marker of microbial pathogenesis and cellular damage in atopic dermatitis

Time course of autoantibodies to collagen type I and III in blood serum and skin exudate in atopic dermatitis

In accordance with Clinical Guidelines of the Russian Society of Dermatovenerologists and Cosmetologists, atopic dermatitis is a chronic allergic genetically determined dermatosis of a multifactorial nature. There are, however, some aspects that challenge the allergic nature of dermatosis. For example, according to literature data, not all the patients have increased synthesis of immunoglobulin E, some of them are torpid to antihistamine treatment, and, when examining the skin of some patients with atopic dermatitis, an absolute polymorphism of rashes is revealed, thus being not typical to the reagin-type allergic reactions. According to modern data, autoimmune theory is assumed for the mechanisms of atopic dermatitis. However, objective proofs of this theory have not been presented, thus drawing our attention to the studies of this issue. The aim of this study was to identify autoimmune pathogenetic mechanisms of atopic dermatitis. The study included 40 adolescents and 40 adult patients with limited and extended forms of atopic dermatitis. The patients were evaluated during the period of exacerbation and remission of the disease. Blood and skin exudates samples were taken from all the patients. The control group consisted of 30 practically healthy volunteers in whom skin exudate was obtained by the “skin window” technique as proposed by Klimov V.V. et al. “A method for assessing minimal inflammatory activity of skin in atopic dermatitis in remission”. Concentrations of IgG autoantibodies to collagen types I and III were determined in blood serum and skin exudate samples applying ELISA techniques with ready-made panels AEA571Hu ELISA Kit for Anti-Collagen Type I Antibody (USA), AEA176Hu ELISA Kit for Anti-Collagen Type III Antibody (USA), according to the manufacturer’s protocols. For the first time, the contents of autoantibodies to skin collagen types I and III in the patients with atopic dermatitis we studied in parallel, i.e., at systemic level and in affected skin. If compared to the group of healthy volunteers, the concentration of autoantibodies to collagen types I and III was found to be increased in all the patients with atopic dermatitis, both during exacerbation and in remission of the disease. The maximal values of autoantibodies to collagen types I and III were recorded in blood serum upon development of clinical symptoms of dermatosis, along with low contents of these antibodies detectable in their skin exudates. Permanently high concentrations of autoantibodies to collagen types I and III in blood serum at exacerbation and remission of atopic dermatitis, and their low level in their skin exudate suggest emergence of circulating and precipitating immune complexes, thus allowing us to consider atopic dermatitis as an autoimmune process

Pathophysiological role of chemokine MIG/CXCL9 in the development of atopic dermatitis

Background. In patients with atopic dermatitis, the persistence of microorganisms on the skin surface is high, which can enhance the expression of MIG/CXCL9, exacerbating inflammation and activating keratinocyte apoptosis, however, the dynamics of this chemokine in atopic dermatitis has not been studied.The aim. To study the concentration of chemokine MIG/CXCL9 in the dynamics of atopic dermatitis and determine its role in the pathogenesis of dermatosis.Materials and methods. The study included 80 patients aged 13 to 44 years with limited and widespread atopic dermatitis and 30 practically healthy volunteers. The therapy of patients, the collection of biological material were carried out in the Regional Dermatovenerologic Dispensary in Chita, laboratory tests were performed at the Chita State Medical Academy in the period from 2018 to 2020. The MIG/CXCL9 level was studied during exacerbation and remission of the disease in blood serum and skin exudate by flow cytofluorimetry using LEGENDplex Human Proinflammatory Chemokine Panel (BioLegend, USA). In healthy volunteers, skin exudate sampling was carried out by the “skin window” method. For statistical processing, the Microsoft Excel (Microsoft Corp., USA) application software package and SPSS Statistics 25.0 (IBM Corp., USA) were used.Results. The concentration of chemokine MIG/CXCL9 in the skin exudate is greater than in the blood serum. With a limited form of the disease in adolescents, the level of MIG/CXCL9 in the skin exudate is 8.1 times higher than the control values, with a common form – 9.3 times. In adults with advanced atopic dermatitis, the concentration of chemokine IL/CXCL9 in the skin exudate is 20.8 times higher than the values of the control group.Conclusion. In atopic dermatitis, the level of chemokine MIG/CXCL9 is higher in the cutaneous pathological process. In the pathogenesis of the disease, MIG/ CXCL9 inhibits collagen synthesis and promotes apoptosis of keratinocytes, followed by the formation of hyperreactivity of the skin, its dryness and peeling