NK cells in patients with chronic rhinosinusitis show decreased maturity and limited expression of functional receptors.

Chronic rhinosinusitis is an inflammatory process of the mucous membrane of the nasal cavity and paranasal sinuses, presenting with two phenotypes that differ in symptoms and inflammatory profiles: either with or without polyps. Natural killer (NK) cells are involved in both the innate and acquired immune response, and their function may be limited under pathological conditions, leading to polyp formation. We determined NK cell involvement and maturity in chronic rhinosinusitis, by determining the percentage of NK cells in polyps, nasal mucosa, and in the peripheral blood. Material was obtained from 49 patients with chronic rhinosinusitis (36 with polyps, 13 without polyps), and 15 control patients. Flow cytometry was used to immunophenotype NK cells, and the expression of selected functional receptors was evaluated. NK cells were found to be increased in polyp tissue versus peripheral blood and nasal mucosa. NK cell maturation differed significantly with predominance of a cytotoxic phenotype (CD11b+/27-) in peripheral blood, compared with a regulatory/tolerogenic phenotype (CD11+/-/ 27+) in tissue material. These findings demonstrate the involvement of NK cells in the inflammatory process of chronic rhinosinusitis. Decreased expression of activating receptors in the analyzed groups may also indicate the presence of modifying agents. Disorders of the maturation process of NK cells may be an important element in the etiopathogenesis of chronic rhinosinusitis with and without polyps.

Comparative proteomic profiling of sera from patients with refractory multiple myeloma reveals potential biomarkers predicting response to bortezomib-based therapy.

INTRODUCTION: In the era of implementing novel agents in multiple myeloma (MM) regimens, drug resistance has become a key factor undermining the results of treatment. Identifying biomarkers allows the prediction of therapy outcomes with specific agents and may lead to the avoidance of resistance. OBJECTIVES: This study aimed to identify biomarkers in the pretreatment sera of patients with refractory/ relapsed MM that differ from those in the sera of patients who achieved a better depth of response with bortezomib-containing therapy. PATIENTS AND METHODS: Pretreatment serum samples were obtained from 61 proteasome inhibitor-naive, transplant-eligible patients who were eligible for salvage PAD (bortezomib, doxorubicin, and dexamethasone) or VTD (bortezomib, thalidomide, and dexamethasone) chemotherapy. Based on their response to therapy, patients were classified into 3 groups: complete or very good partial response, partial response, and progressive or stable disease. A comparative proteomic analysis of the groups was performed. RESULTS: The analyzed groups significantly differed in terms of both overall survival and progression­free survival. In total, 632 proteins were identified. The proteomic signature revealed 54 proteins that differentiated each analyzed experimental group. Functional analysis revealed that the main identified pathways (17 proteins) involved the regulation of hydrolase activity and cellular response to stimuli. The identified proteins included apolipoprotein C1, complement components, and sulfhydryl oxidase 1. CONCLUSIONS: Our results demonstrated that the label-free proteomic analysis is a useful method for describing proteins differentially expressed in the sera of patients with MM. Further studies are needed to analyze the use of identified proteins as biomarkers.