RESUMO
Sarcoidosis is a rare granulomatous disease of unknown aetiology belonging to the wide group of interstitial lung diseases.). Although the limitlessness of BAL fluid is debated, it remains one of the best matrices for studying the pathogenesis of sarcoidosis. Natural killer (NK) cells have been described in BAL fluid from sarcoidosis patients. Elevated NK cells in BAL fluid from sarcoidosis patients have been found to be associated with poor outcomes. In this study, NK cells were evaluated in BAL samples from sarcoidosis patients at the time of diagnosis and associated with clinical characteristics in order to evaluate their prognostic role. Of the 276 patients suspected to have sarcoidosis on the basis of clinical and radiological findings, 248 had a final diagnosis of sarcoidosis. Clinical parameters, Scadding stage, and extrapulmonary localization were collected in a database. It resulted in fibrotic sarcoidosis patients being associated with an increase in lymphocyte percentages in BAL samples, particularly NK cells when compared with other groups. From ROC analysis, NK cell percentages in BAL samples resulted as being the best predictive markers in discriminating stage 4 of sarcoidosis from other RX stages (AUC=0.85, p<0.0001). Furthermore, after the stratification of patients on the basis of the number of extrapulmonary localizations, patients with an higher number of extrapulmonary localizations also showed higher percentages of NK cells in BAL fluid. In conclusion, NK cell percentages in BAL fluid can be considered a good prognostic marker of fibrotic phenotypes of sarcoidosis and involvement of other organs, although their diagnostic utility was poor.
RESUMO
ABTRACT: Background The pathogenetic and regulatory roles of natural killer (NK) and natural killer T-like cells in interstitial lung diseases (ILDs), fibrotic and granulomatous of unknown etiology are unclear. Objectives Here we investigated NK and NKT-like cells in peripheral blood (PB) and Bronchoalveolar lavage (BAL) from patients with ILDs. Method 190 patients (94 male mean age 61 ± 14.3 years) and 8 controls undergoing bronchoscopy for ILD diagnostic work-up were enrolled consecutively; 115 patients sarcoidosis, 24 chronic fibrotic hypersensitivity pneumonitis and 43 patients other ILDs [32 idiopathic pulmonary fibrosis (IPF) and 11 non-specific interstitial pneumonia (NSIP)]. PB and BAL were processed by flow cytometry using monoclonal antibodies to differentiate NK and NKT-like cells. Results NK% in BAL was significantly different among ILDs (p = 0.02). Lower NK% was observed in BAL from sarcoidosis than other ILDs (p < 0.05). Similar findings were observed for NKT-like, whereas no differences were found for PB NK%. Difference of NK% was observed between BAL and PB in all groups (p < 0.001). Sarcoidosis patients reported the best area under the curve for NKT-like (AUC = 0.678, p = 0.0015) and NK cells (AUC = 0.61, p = 0.001). In the IPF-NSIP subgroup, NK% cell was inversely correlated with FVC% (r = - 0.34, p = 0.03) and DLCO% (r = - 0.47, p = 0.0044). Conclusions NK and NKT-like were expressed differently in BAL from patients with different ILD and were significantly depleted in sarcoidosis respect to other ILDs. This suggests that these cells may play a protective role in the pathogenesis of sarcoidosis.