Lymphocyte expression of human leukocyte antigen class II molecules in patients with chronic obstructive pulmonary...

Chronic obstructive pulmonary disease (COPD) is a multifactorial disorder, deriving from a combination of environmental and genetic factors. Polymorphisms of genes of the human major histocompatibility complex in COPD have been poorly studied in the past. In a preliminary approach, it was difficult to type human leukocyte antigen (HLA) at the protein level and it was hypothesized that there was a reduced surface density of HLA class II molecules. The aims of this study were to analyse, by cytofluorimetry, HLA class I and II molecule densities on peripheral mononuclear cells of COPD patients and to investigate whether there was a correlation with the polymorphisms of DQA and DQB promoter regions which are supposed to be important factors involved in surface expression of HLA-DQ molecules. The study investigated 27 male COPD patients admitted because of disease exacerbation and 49 healthy male controls. Quantitative analysis of fluorescence intensity of HLA class I (A, B, C) and class II (DR, DP, DQ) molecules was performed on blood mononuclear cells by cytoron cytofluorimetry. Polymorphisms of DQA and DQB promoters (QAP and QBP) were determined from the DNA (PCR-SSO). The surface densities of HLA class I and HLA-DQ molecules did not differ between the COPD patients and controls. HLA-DP molecule density seemed to be slightly, but not significantly lower in COPD, whereas surface HLA-DR molecules were significantly reduced (p < 0.005 vs controls). Frequencies of QAP alleles were not different between the COPD patients and controls, but the QBP 5.12 allele was significantly more frequent in COPD than in controls (chi 2 = 10.83, p = 0.0182, RR 5.5). In conclusion, individuals with exacerbated chronic obstructive pulmonary disease have reduced surface DR molecule expression and an increased frequency of the QBP 5.12 allele. The possible relationship between these two features and the possible role of cytokines in reducing human leukocyte antigen-DR expression in exacerbated chronic obstructive pulmonary disease is explored.