Soluble Immune-Related Proteins as New Candidate Serum Biomarkers for the Diagnosis and Progression of Lymphangioleiomyomatosis

BACKGROUND: The goal of this study was to analyze serum from lymphangioleiomyomatosis (LAM) patients and healthy controls to identify novel biomarkers that could shed light on disease diagnosis and pathogenesis. METHODS: From April 2017 to October 2019, qualified serum samples were obtained to explore differences in 59 immune proteins between 67 LAM patients and 49 healthy controls by the Luminex method. RESULTS: We characterized 22 serum immune proteins that were differentially expressed in LAM patients compared with healthy people. Fifty-nine proteins were then classified into eight categories according to their biological function, and the results showed that LAM patients displayed significantly higher levels of growth factors (p = 0.006) and lower levels of costimulatory molecules (p = 0.008). LAG-3 was not only likely to have better predictive value than VEGF-D but also showed a significant difference between patients without elevated VEGF-D and healthy people. IL-18 was positively correlated with lung function and six-minute walk test (6MWT) distance and negatively correlated with St. George’s Respiratory Questionnaire (SGRQ) score and pulmonary artery systolic pressure (PASP), which suggested that IL-18 was related to disease severity. PD-1 was significantly different between patients with pneumothorax and/or chylothorax and those without complications. CONCLUSION: We performed a large-scale serum immune factor analysis of LAM. Our study provides evidence that LAG-3 may be a novel candidate serum biomarker for the diagnosis of LAM. Future independent validation in prospective studies is warranted.