The polymorphisms of IL-6/STAT3 signaling pathway may contribute to cutaneous T-cell lymphomas susceptibility

Berenika Olszewska,Małgorzata Sokołowska-Wojdyło,Roman J Nowicki,Monika Zabłotna,Jolanta Gleń

doi:10.1007/s00403-020-02062-5

Berenika Olszewska, Małgorzata Sokołowska-Wojdyło + Show 3 more

Open Access

https://doi.org/10.1007/s00403-020-02062-5

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Abstract

IL-6/STAT3 signaling pathway has been suggested to play a role in CTCL pathogenesis. Polymorphisms in STAT3 signaling pathway-related genes might be a risk factor for CTCL. However, the exact role of inherited gene polymorphisms of IL-6 and STAT3 in the pathogenesis of CTCL is still not fully understood. The aim was to examine whether IL-6 cytokine and polymorphisms of IL-6 and STAT3 gene are associated with CTCL susceptibility, stage of disease and pruritus intensity. We compared the IL-6 serum level and the frequency of selected single nucleotide polymorphisms of IL-6 and STAT3 in 106 CTCL and 198 control group using polymerase chain reaction with sequence-specific primers method and ELISA. We have found that serum IL-6 level in CTCL patients was significantly higher than in healthy controls (p < 0.05). We also demonstrated that two genotypes, CC of IL-6 and GG of STAT3, were overexpressed in CTCL patients compared to healthy controls, and that they increase the risk of malignancy development (OR = 1.8, p = 0.04 for IL-6 and OR 2.53, p = 0.0064 for STAT3). Moreover, the GG genotype of STAT3 polymorphism seems to be associated with lack of pruritus or mild pruritus in CTCL patients. Our results indicate that IL-6 is involved in pathogenesis of CTCL but not pruritus. Moreover, CC of IL-6 and GG genotype of STAT3 genes might be considered as the risk factor for development of CTCL.

Highlights

Cutaneous T-cell lymphomas (CTCLs) comprise a clinically heterogeneous group of malignant limfoproliferative disorders
The median and mean ± SD serum IL-6 levels in CTCL patients were significantly higher than in healthy controls (6.85 ± 8.78 pg/ml; 4.31 pg/ml; range: 0.14–53.0 compared to 1.4 ± 1.28 pg/ml; 1.05 pg/ml; range: 0.08–6.27; p < 0.05) (Fig. 1)
There were no statistically significant differences in serum IL-6 level between pruritic and non-pruritic CTCL patients (VAS p = 0.71; numerical analog scale (NRS) p = 0.84) No positive correlation was found between serum IL-6 levels and severity of pruritus in CTCL (VAS p = 0.68; NRS p = 0.58)

Summary

Introduction

Cutaneous T-cell lymphomas (CTCLs) comprise a clinically heterogeneous group of malignant limfoproliferative disorders. Most common subtypes are mycosis fungoides (MF) and Sezary syndrome (SS), an aggressive variant of CTCL [1]. CTCLs are characterized by cutaneous infiltrates of malignant CD4 + CD45RO + skin-homing T cells, eosinophilia and high levels of immunoglobulin E. MF display varying degrees of inflammation, early stage presents limited patches or plaques; they can eventually evolve into tumors or erythroderma [1, 2]. The disease can further disseminate to the lymph nodes, blood and visceral organs [1, 2]. There are a few hypotheses of CTCL pathogenesis, including viral etiology or chronic antigen stimulation, e.g., exposure to UV radiation or bacterial superantigens such as S. aureus

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