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Background: Three subpopulations of monocytes can be distinguished in human blood: classical (CD14++CD16-), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++). CD16 expressing monocytes are expanded in patients with sarcoidosis and in various other inflammatory diseases. In sarcoidosis, it is unclear whether either intermediate, nonclassical or both CD16 expressing monocytes are responsible for this increase. Data relating to the monocyte subpopulations is receiving increasing attention, but the expression of TNF receptors on these subpopulations has not been studied thus far. The aim of this study was to determine frequencies of monocyte subpopulations and their expression of TNFR1 and TNFR2 in both sarcoidosis patients and healthy controls. Methods: Peripheral blood cells of sarcoidosis patients and healthy controls were stained for the markers HLA-DR, D14, CD16, CD120a and CD120b. Cells were measured on a FACSCalibur and analyzed with FlowJo. We used Student's t-test and a parametric One-way ANOVA for statistical analysis. Results: Sarcoidosis patients had a significant higher frequency of intermediate monocytes than healthy controls. Significant differences in TNF receptor expression were found between the monocyte subpopulations, both in sarcoidosis patients as well as in healthy controls: intermediates expressed more TNFR1 than classicals and nonclassicals and nonclassicals expressed more TNFR2 than intermediates, whereas intermediates showed higher expression than classicals. Conclusions: In both sarcoidosis patients and healthy controls intermediate monocytes show the highest expression level of TNFR1 among monocyte subpopulations and nonclassical monocytes show the highest expression level of TNFR2. These findings, as wells as the higher frequency of intermediate monocytes in sarcoidosis patients, provide evidence for the existence of two functionally-distinct CD16 expressing monocyte subpopulations. [ABSTRACT FROM AUTHOR]

Inconclusive evidence for the efficacy of infliximab in sarcoidosis hinders the global use of this potentially beneficial drug. To study infliximab efficacy in a clinical setting, we performed a prospective open-label trial in patients refractory to conventional treatment. Patients (n=56) received eight infusions of 5 mg·kg(-1) infliximab. Pulmonary function, disease activity measured by (18)F-fluorodeoxyglucose (FDG) by positron emission tomography (PET) and quality of life were part of the clinical work-up. Infliximab levels were measured before every infusion. After 26 weeks of infliximab treatment, mean improvement in forced vital capacity (FVC) was 6.6% predicted (p=0.0007), whereas in the 6 months before start of treatment, lung function decreased. Maximum standardised uptake value (SUVmax) of pulmonary parenchyma on (18)F-FDG PET decreased by 3.93 (p<0.0001). High SUVmax of pulmonary parenchyma at baseline predicted FVC improvement (R=0.62, p=0.0004). An overall beneficial response was seen in 79% of patients and a partial response was seen in 17% of patients. No correlation between infliximab trough level (mean 18.0 µg·mL(-1)) and initial response was found. In conclusion, infliximab causes significant improvement in FVC in refractory (18)F-FDG PET positive sarcoidosis. Especially in pulmonary disease, high (18)F-FDG PET SUVmax values at treatment initiation predict clinically relevant lung function improvement. These results suggest that inclusion of (18)F-FDG PET is useful in therapeutic decision-making in complex sarcoidosis., (Copyright ©ERS 2015.)