Tumor necrosis factor receptors (TNFRs) on T lymphocytes and soluble TNFRs in different clinical courses of sarcoidosis

Abstract

The release of tumor necrosis factor (TNF-alpha) is increased in sarcoidosis patients. TNF-alpha exerts its effect by binding to specific cell surface receptors. There are only fragmentary data concerning the expression of tumor necrosis factor receptors (TNFRs) on bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) lymphocytes. The aim of the study was to evaluate TNFRI (CD120a) and TNFRII (CD120b) expression on T cells and the level of soluble TNFRs in specimens of patients with different clinical manifestation and clinical outcome of sarcoidosis. We examined 49 patients with newly diagnosed pulmonary sarcoidosis. TNFRI and TNFRII density on CD4+ and CD8+ BALF and PB cells surface was estimated using monoclonal antibodies and a flow cytometry technique. The level of TNFRs in PB serum and BALF cell culture supernatant (CCS) was measured using ELISA. Immunological analyses were also performed on PB samples collected from 10 healthy volunteers. The level of soluble TNFRI (sTNFRI) in PB serum was similar in sarcoidosis patients and healthy subjects, whereas the concentration of sTNFRII in serum was significantly higher in the sarcoidosis group (P<0.001). Patients without acute symptoms of sarcoidosis, patients with radiological stage II/III as well as patients with further disease progression showed a tendency to higher levels of sTNFRs in PB serum and lower levels of sTNFRs in BALF CCS compared to Löfgren syndrome and radiological stage I subjects, and patients with spontaneous resolution of sarcoidosis. More than 80% of BALF and PB lymphocytes of sarcoidosis patients expressed both CD120a and CD120b antigens. The percentage of double-positive CD4+CD120a+ and CD4+CD120b+ cells in PB was significantly higher (P<0.005) in sarcoidosis patients than in healthy subjects. The highest percentage of CD4+CD120a+ and CD4+CD120b+ lymphocytes in BALF was determined in patients with acute disease, and in PB of patients with further spontaneous improvement. The evaluation of sTNFRs and TNFRs expression on T-helper cells may be useful in the estimation of sarcoidosis activity.