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

Xuefei Liu,Xueying Wu,Qiang Wu,Min Zhou,Henghui Zhang,Yanpu Liu,Jieming Qu,Jialiang Wu,Yanping Xu

doi:10.3389/fimmu.2022.844914

Abstract

BackgroundThe 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.MethodsFrom 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.ResultsWe 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.ConclusionWe 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.

Highlights

Lymphangioleiomyomatosis (LAM) is a rare and progressive cystic lung disease that occurs almost exclusively in women of reproductive age [1]
Previous studies reported that LAM patients often had pulmonary hypertension and decreased cardiopulmonary function [26–28], so we collected the patient’s pulmonary artery systolic pressure (PASP), six-minute walk test (6MWT), St
The results showed that the level of PD-1 in the subgroup without complications was lower than that in the subgroup with complications (p=0.015) (Figure 4A)

Summary

Introduction

Lymphangioleiomyomatosis (LAM) is a rare (affecting approximately five per million) and progressive cystic lung disease that occurs almost exclusively in women of reproductive age [1]. LAM is characterized by excessive proliferation of atypical smooth muscle-like cells (LAM cells) and cystic destruction of the lung parenchyma. Many studies have found that excessive proliferation of LAM cells leads to lymphatic vascular malformation, which is related to the involvement of vascular endothelial growth factor D (VEGF-D) in the occurrence of the disease [8–11]. Serum VEGF-D can be used as a noninvasive biomarker for the diagnosis and disease activity of LAM. 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

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Conclusion