Reduced Th1 response in the lungs of HLA-DRB1*0301 patients with pulmonary sarcoidosis.
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)-gamma and interleukin (IL)-10 mRNA. There were significantly decreased IFN-gamma and tumour necrosis factor (TNF)-alpha mRNA levels, and a tendency toward higher levels of transforming growth factor-beta1 mRNA in HLA-DRB1*0301 positive compared with HLA-DRB1*0301 negative patients. Protein levels of IL-1beta, IL-2, IL-6, IL-12p70 and TNF-alpha in BALF were significantly higher in patients. HLA-DRB1*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-DRB1*0301 positive patients, which may relate to their good prognosis.
Idali
F
F
Dept of Medicine, Division of Respiratory Medicine, Immune and Gene Therapy Laboratory, Karolinska University Hospital, Solna, 171 76 Stockholm, Sweden. Farah.Idali@medks.ki.se
Wikén
M
M
Wahlström
J
J
Mellstedt
H
H
Eklund
A
A
Rabbani
H
H
Grunewald
J
J
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis / Q000096:biosynthesis*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D017565:Sarcoidosis, Pulmonary / Q000276:immunology*; D018417:Th1 Cells / Q000502:physiology*
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen