Soluble B7h3 Induction In Pulmonary Fibrosis Is Associated With Disease Severity

Abstract Idiopathic pulmonary fibrosis (IPF) is a progressive disease with limited therapeutic options. Both innate and adaptive immune mechanisms contribute to fibrogenesis. B7 family member B7H3, identified as important regulator of the immune system, has been implicated in cancer, graft-versus host disease, and allergy-related disease. Increased soluble B7H3 (sB7H3) was associated with enhanced lung fibrosis in mice receiving BLM-primed BM. Elevated sB7H3 in bronchoalveolar lavage fluid was associated with acute exacerbation IPF. To investigate whether induced sB7H3 could be used as a biomaker for IPF diagnosis and/or prognosis, plasma sB7H3 from control subjects and IPF patients was measured by ELISA. Its correlation with peripheral blood immune cells, lung function, and drug treatments were evaluated in this study. The results showed that the sB7H3 level was significantly elevated in IPF patients. This induction was associated with increased circulating B7H3+ cells, and significantly correlated with increased granulocytic myeloid-derived suppressive cells (G-MDSCs). This suggests a potential regulatory role of the induced B7H3 in the immune response in IPF. The plasma sB7H3 was negatively correlated with lung function measured as diffusing capacity of the lungs for carbon monoxide (DLCO), indicating the potential utility of plasma sB7H3 as an indicator of disease severity. The slightly elevated sB7H3 in the pirfenidone and/or nintedanib treated IPF patients were not significantly different relative to controls, which was in contrast to the significant elevation noted for the untreated patients. These findings suggest that sB7H3 may be a useful biomarker for clinical assessment of prognosis and response to drug treatment.