Abstract
Rationale: Blockade of TNF by infliximab can be effective as third-line treatment for severe sarcoidosis. Monocyte subsets have differential expression of TNF-receptors 1 and 2 (TNFR1 and TNFR2). The effect of infliximab on monocytes is unknown.
Methods: In this prospective study we collected serum of 38 patients during infliximab treatment and 18 healthy controls. Blood cells were stained for HLA-DR, CD14, CD16, CCR2, CCR5, TNFR1 and TNFR2 and analyzed by flow cytometry.
Results: The percentage of monocytes at baseline correlated positively with disease activity as measured by sIL-2R at baseline (R=0.47; p=0.003), ACE at baseline (R=0.43; p=0.014) and negatively with change in ACE during therapy (R=0.56; p=0.001).
Monocytes were classified as classical, intermediate or nonclassical, based on CD14 and CD16 expression. The percentage of intermediates at baseline was higher in patients than in controls (3.2% vs 1.8%; p<0.0001) and increased after 14 weeks of therapy (3.2% vs 4.1%; p=0.010), but fell back to baseline at week 26. During therapy, the percentage of nonclassicals decreased from 15.6% to 12.3% (p=0.0063). Furthermore, the percentage of TNFR1 expressing classicals decreased from 59.8% to 43.6% (p=0.0065), while TNFR2 expression remained stable. Mean CCR5 expression increased on intermediates from 40.3% to 46.4% (p=0.03), and on nonclassicals from 7.5% to 11.6% (p=0.001).
Conclusions: During infliximab therapy, the percentage of nonclassicals decreases significantly. Furthermore, changes in expression of TNFR1 and CCR5 expression were seen. Our findings suggest a differential role for monocyte subsets in sarcoidosis.
- Copyright ©ERS 2015
