The Study On Th17 Cells And IL-17 Expression And The Association With MUM1/IRF4 In Multiple Myeloma

ObjectiveTh17 cells are novel CD4+ T helper cells which participate in the inflammation and autoimmunity and play an important role in protecting the body escape from infections of parasites and fungus. IL-17 is secreted by Th17 cells and used as a marker. Recent studies have shown that Th17 cells and related cytokines of multiple myeloma (MM) patients were significantly higher than healthy donor. The differentiation and development of Th17 cells are related to Treg cells closely. IL-17 acts on promoting the proliferation of myeloma cells, but the mechanism is still unclear. MUM1/IRF4 is a member of the Interferon Regulatory Factor family, it is highly expressed in MM and have an effect on prognosis of MM. MUM1/IRF4 also plays an important role in the differentiation of Th17 cells. This study aims to explore Th17 cells and IL-17 expression and the association with MUM1/IRF4 in multiple myeloma.MethodsA total of 58 MM patients were collected from the First Affiliated Hospital of Nanjing Medical University from January 2012 to March 2014. These patients were divided into 2 groups,38 cases of newly diagnosed MM patients were in group 1,20 cases of relapsed MM patients were in group 2. There were 20 healthy donors who were diagnosed without autoimmune disease, cancer or infection. Flow cytometry was used to detect the proportion of Th17 cells and Treg cells in peripheral blood of MM patients and healthy donors. The serum IL-17 level was measured by enzyme-linked immunosorbent assay. The expression of IRF4 in bone marrow of MM patients was detected by immunohistochemistry (IHC).ResultsThe Th17 cells and Treg cells of peripheral blood was significantly increased in newly diagnosed and relapsed MM patients (p< 0.05) while the Th17 cells of newly diagnosed MM patients was higher than relapsed patients without statistically significance (p> 0.05). The Treg cells of relapsed MM patients was increased than newly diagnosed MM (p< 0.01), the proportion of Treg cells was positively correlated with serum calcium level (r= 0.359, p= 0.048). The serum IL-17 level of newly diagnosed and relapsed MM patients was higher than healthy donors (p< 0.05) which was in keeping with the proportion of Th17 cells. The serum IL-17 level of patients who diagnosed at Durie-Salmon Criteria group B was elevated with statistically significance than group A (p< 0.05).65.5% of MM patients expressed IRF4, the expression level of patients in stage Ⅲ was significantly higher than patients in stages Ⅰ and Ⅱ (Durie-Salmon Criteria,p< 0.05; ISS Criteria,p< 0.01). We concluded higher expression level of IRF4 is associated with adverse prognosis. The proportion of Th17 cells and serum IL-17 level was positively correlated with the intensity of IRF4 in MM patients (r= 0.379, p= 0.027; r= 0.406, p= 0.011).ConclusionsThe Th17 cells of peripheral blood and serum IL-17 level is significantly increased in MM patients, the serum IL-17 level of patients who diagnosed at Durie-Salmon Criteria group B is elevated with statistically significance than group A. The proportion of Th17 cells and serum IL-17 level is positively correlated with the intensity of IRF4 in MM patients. MUMI/IRF4 may play an important role in MM by promoting the secretion of IL-17 in Th17 cells.