Validation of Soluble Programmed Death-1 in Predicting Progression of Nodular-bronchiectatic Form of Nontuberculous Mycobacterial Lung Disease: a Multi-Country Research

Overview

The incidence of nontuberculous mycobacterial lung disease (NTM-LD) is increasing worldwide and in Eastern Asia. NTM-LD leads significant morbidity and mortality, around 25% within 5 years, but the treatment rate is low because the course of NTM-LD is indolent, especially in nodular-bronchiectatic (NB) form. However, there is no biomarker proven for predicting the progression in NB form of NTM-LD. Recently, it has been reported that the ratio of membrane-form programmed death-1 (PD-1) expressed T cells increased in patients with NTM-LD and it was associated with disease severity and progression. The mechanism has been speculated as a "immune exhaustion". In contrast to PD-1 expressed in cell membrane, soluble-form PD-1 is another biomarker that can be easily detected in serum. We recently reported that soluble PD-1 significantly correlated with cavitary lesion and disease progression in patients with NB-form NTM-LD in Taiwan. However, this has not been validated in other countries and ethnicities. Furthermore, the usefulness of soluble PD-1 in diagnosis and predicting mortality warrants further studies.

The incidence of nontuberculous mycobacterial lung disease (NTM-LD) is increasing worldwide and in Eastern Asia. NTM-LD leads significant morbidity and mortality, around 25% within 5 years, but the treatment rate is low because the course of NTM-LD is indolent, especially in nodular-bronchiectatic (NB) form. However, there is no biomarker proven for predicting the progression in NB form of NTM-LD. Recently, it has been reported that the ratio of membrane-form programmed death-1 (PD-1) expressed T cells increased in patients with NTM-LD and it was associated with disease severity and progression. The mechanism has been speculated as a "immune exhaustion". In contrast to PD-1 expressed in cell membrane, soluble-form PD-1 is another biomarker that can be easily detected in serum. We recently reported that soluble PD-1 significantly correlated with cavitary lesion and disease progression in patients with NB-form NTM-LD in Taiwan. However, this has not been validated in other countries and ethnicities. Furthermore, the usefulness of soluble PD-1 in diagnosis and predicting mortality warrants further studies. Moreover, it is worthwhile to measure soluble PD-1 in bronchoalveolar lavage to explore local immune pathogenesis of NTM-LD. Therefore, we apply this project to investigate the role of soluble PD-1 in NTM-LD through a multi-country cooperation.