Reduced Th1 response in the lungs of HLA-DRB1*0301 patients with pulmonary sarcoidosis

Abstract

To investigate why human leukocyte-associated antigen-DRB1*0301 (HLA-DRB1* 0301) positive Scandinavian patients have a better prognosis than HLA-DRB1*0301 negative patients, the present authors examined patterns of cytokine expression in bronchoalveolar lavage (BAL) cells and BAL fluid (BALF) from patients with pulmonary sarcoidosis and controls. Using real-time PCR, the mRNA expression of selected cytokines in BAL cells from newly diagnosed, untreated nonsmoking patients (n=25) and controls (n=11) was quantified. Cytokine protein levels in BALF from patients (n=34) and controls (n=11) were assessed using cytometric bead array. The patients were evaluated and stratified into two subgroups: HLA-DRB1*0301 positive (all with an acute onset) and HLA-DRB1*0301 negative (all with an insidious onset). When comparing patients and controls, BAL cells of the patients expressed significantly higher levels of interferon (IFN)-γ and interleukin (IL)-10 mRNA. There were significantly decreased IFN-γ and tumour necrosis factor (TNF)-α mRNA levels, and a tendency toward higher levels of transforming growth factor-β1 mRNA in HLA-DRB1*0301 positive compared with HLA-DRB1*0301 negative patients. Protein levels of IL-1β, IL-2, IL-6, IL-12p7O and TNF-α in BALF were significantly higher in patients. HLA-DR131*0301 positive patients exhibited tendencies to lower levels of most cytokines in BALF. In conclusion, the present data show a reduced expression of T-helper cell type-1 cytokines in human leukocyte-associated antigen-DRBI*0301 positive patients, which may relate to their good prognosis. Copyright © ERS Journals Ltd 2006.