The Expression And Significance Of Hypoxia Inducible Factor-1α And Th1/Th2/Th17 Subsets Cytokines In Pretibial Myxedema

Background and objective:Pretibial myxedema is a disease of mucinosis under the background of autoimmune thyroid disease.The main manifestations of pretibial myxedema could be characterized by non-pitting swelling,nodules,plaques and elephantiasic legs,the most common lesions locates at the pretibial area.Abnormal deposition of abundant hyaluronic acid in the dermis is the main pathological feature of pretibial myxedema,but the precise pathogenesis has not been clarified.Current research revealed that local factors of lower extremity(trauma and stasis posture)may play important roles in the occurrence and development of the disease,and the possible mechanism may refer to the disorder of microcirculation,the accumulation of inflammatory media and the hypoxia of local tissue.Hypoxia inducible factor-1α accumulates in cells under hypoxic condition,mediating cellular biological behaviors including inflammation and immunity.It also plays an significant role in the differentiation of CD4+T cells.CD4+T cells can differentiate into different helper lymphocyte subsets,such as Th1,Th2,and Th17.These subsets and the proinflammatory cytokines they secreted play important roles in the process of mediating cellular immune,humoral immune and autoimmune respectively.The purpose of this study was to preliminarily explore the expression and possible significance of HIF-1α and cytokines secreted by Th1/Th2/Th17 subsets in pretibial myxedema,to further elaborate on the mechanism of local factors involved in the initiate and development of pretibial myxedema,and to lay the foundation for exploring new therapeutic methods.Materials and Methods:In this study,a total of 10 paraffin samples of PTM lesions and 10 paraffin samples of normal skin,6 patients of pretibial myxedema and 6 healthy volunteers were included.Detailed demographic and medical records were recorded,all subjects gave informed and signed consent to participate in the study.1.Immunohistochemical staining and qRT-PCR were used to analyze the expression differences of HIF-1α between pretibial myxedema lesions and normal skin.2.Flow cytometry was used to analyze the concentration differences ofinflammatory cytokines of Th1/Th2/Th17 subsets in peripheral blood and tissue fluid from pretibial myxedema patients and normal persons.3.SPSS24.0 software was used for statistical analysis.The data obtained in this study were expressed as mean±standard deviation(x ±s)or the distance between the median and the quartile: M(P25,P75).The independent samples t test or the non-parametric Wilcoxon rank sum test were used for the inter-group comparison.When P <0.05,the difference was considered statistically significant,and when P<0.01,the difference had obvious statistical significance.Result:1.Immunohistochemical staining showed HIF-1α was mainly expressed in the dermis of pretibial myxedema lesions,but hardly expressed in normal skin.The histochemical score of lesions was higher than that of normal skin(P<0.01).The result of qRT-PCR demonstrated the HIF-1α mRNA relative expression levels in pretibial myxedema lesions was higher than normal skin(P<0.05).2.The levels of IL-6 and IL-17 A in lesion tissue fluid of pretibial myxedema patients were higher than those in their own peripheral blood(P<0.05);The levels of IL-6 and IL-17 A in lesion tissue fluid of pretibial myxedema patients were higher than those in pretibial tissue fluid of normal persons(P<0.05).Conclusion:Our study found HIF-1α was high expressed in pretibial myxedema lesions,and IL-6 and IL-17 A were high expressed in lesion tissue fluid,which confirmed that pretibial myxedema is an autoimmune skin disease with involvement of IL-6 and IL-17 A,limited inflammation and local tissue hypoxia.Changing the postures of both lower extremities frequently,avoidance of trauma,improving the microcirculation of both lower extremities and the microenvironment of local hypoxia may have positive effects on the treatment and remission of pretibial myxedema.In-depth study on the functions of Th1/Th2 and Th17/Treg and the mechanisms that maintain the balance may provide new therapeutic strategies for the treatment of pretibial myxedema.