Decreased Expression of Hla-Dq and -Dr on Blood Monocytes, Sputum Macrophages and Monocytederived Macrophages in Patients Eth Cystic Fibrosis

We studied HLA class II molecules in adult patients with cystic fibrosis (CF) and healthy subjects at the protein level (flow cytometry) and mRNA level (RT-PCR) in blood monocyte subsets, sputum macrophages and monocyte-derived macrophages as putative contributors to the CF phenotype. In healthy donors we found a high average HLA-DQ expression of 4.35 mean specific fluorescence intensity (ΔMnI) on classical blood monocytes, with the lowest value of 2 ΔMnI. In F508del homozygous CF patients the average ΔMnI was low (1.80). 14 of these patients had HLA-DQ expression above 2 ΔMnI (average 3.25 ΔMnI, CF-DQ group1 ) and 36 below (average 1.24 ΔMnI, CF-DQ group2 ). In healthy controls the CD16-positive monocyte subset expressed higher levels of HLA-DQ (10.88 ΔMnI) when compared to the classical monocytes but again the CF-DQ group2 patients showed much lower levels for HLA-DQ on these cells (2.48 ΔMnI). DQ expression levels on sputum macrophages and monocyte-derived macrophages (MDM) exhibit dramatically decreased levels in the CF-DQ group2 cases. At mRNA level we found a seven-fold decrease for DQβ1 transcripts in monocytes from the CF-DQ group2 patients. CRP levels of the patients are correlated with low HLA-DQ (p=0.024) and -DR (p=0.0007) protein expression. In vitro HLA-DQ and -DR expression on blood monocytes was also decreased after LPS-treatment (p The data demonstrate that CF patients showed reduced expression of MHC class II molecules in monocytes and macrophages, which is most pronounced for HLA-DQ both at the mRNA and protein level an.