Abstract
The skin barrier defect in cutaneous T-cell lymphomas (CTCL) was recently confirmed to be similar to the one observed in atopic dermatitis (AD). We have examined the expression level of cornified envelope (CE) proteins in CTCL, AD and healthy skin, to search for the differences and their relation to the courses of both diseases. The levels of FLG, FLG2, RPTN, HRNR, SPRR1A, SPRR1B, SPRR3 and LELP-1 mRNA were determined by qRT-PCR, while protein levels were examined using the ELISA method in skin samples. We have found that mRNA levels of FLG, FLG2, LOR, CRNN and SPRR3v1 were decreased (p ≤ 0.04), whereas mRNA levels of RPTN, HRNR and SPRR1Av1 were increased in lesional and nonlesional AD skin compared to the healthy control group (p ≤ 0.04). The levels of FLG, FLG2, CRNN, SPRR3v1 mRNA increased (p ≤ 0.02) and RPTN, HRNR and SPRR1Av1 mRNA decreased (p ≤ 0.005) in CTCL skin compared to the lesional AD skin. There was a strong correlation between the stage of CTCL and increased SPRR1Av1 gene expression at both mRNA (R = 0.89; p ≤ 0.05) and protein levels (R = 0.94; p ≤ 0.05). FLG, FLG2, RPTN, HRNR and SPRR1A seem to play a key role in skin barrier dysfunction in CTCL and could be considered a biomarker for differential diagnosis of AD and CTCL. SPRR1Av1 transcript levels seem to be a possible marker of CTCL stage, however, further studies on a larger study group are needed to confirm our findings.
Highlights
Cutaneous T-cell lymphomas (CTCLs) represent a rare heterogeneous group of extranodal non-Hodgkin lymphomas
We have found significantly lower levels of FLG, FLG2, LOR and CRNN mRNA in lesional and nonlesional atopic dermatitis (AD) skin compared to the healthy control group (p ≤ 0.02). mRNA level of SPRR3v1 was decreased in AD samples, only in lesional skin (p ≤ 0.00008)
Our study has revealed decreased mRNA expression of FLG, FLG2, LOR, CRNN and SPRR3v1 concomitant with increased LELP1, RPTN, HRNR and SPRR1Av1 mRNA levels in AD compared to healthy controls, which is in line with previous findings [15,16,17,21,22,23,24]
Summary
Cutaneous T-cell lymphomas (CTCLs) represent a rare heterogeneous group of extranodal non-Hodgkin lymphomas. The inflammatory microenvironment of the skin seems to play a crucial role in CTCL pathogenesis, as the predominance of Th2 over Th1 cells in inflammatory microenvironment seems to be responsible. The clinical presentation and immunological features are overlapping Both MF and AD show infiltration of the skin by skin-homing T-cells [10,11]. The malignant T-cells were reported to be responsible for changes in the epidermis in CTCL and impaired epidermal barrier function [13]. Skin infections have been a significant clinical problem both in AD and in CTCL as a result of compromised skin barrier and a progressive immunodeficiency in CTCL. In the face of so many similarities between CTCL and AD, evaluation of expression of genes encoding the cornified envelope (CE) proteins such as the late cornified envelope-like proline-rich protein-1 (LELP-1), small proline-rich proteins (SPRR1A, SPRR1B, SPRR3), repetin (RPTN), cornulin (CRNN), hornerin (HRNR), loricrin (LOR) and filaggrin (FLG, FLG2) might provide accurate information and findings to differentiate those diseases and determine their relation to the course and development of both diseases
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