Decoding the Immune Response and Its Biomarker B2M for High Altitude Pulmonary Edema in Rat: Implications for Diagnosis and Prognosis

Abstract

Mu Yuan,1,2,* Weijun Wan,1,2,* Wei Xing,1,2 Chengxiu Pu,1,2 Xiaofeng Wu,1,2 Zhikang Liao,3 Xiyan Zhu,3 Xueting Hu,1,2 Zhan Li,1,2 Qing Zhao,1,2 Hui Zhao,3,* Xiang Xu1,2,* 1Department of Stem Cell and Regenerative Medicine, National Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 2Central Laboratory, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 3Research Department Fourth Laboratory, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiang Xu, Stem Cell and Regenerative Medicine Department, Daping Hospital, Army Medical University, Chongqing, No. 10, Changjiang Road, Yuzhong District, Chongqing, 400042, People’s Republic of China, Email [email protected] Hui Zhao, Research Department Fourth Laboratory, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China, Email [email protected]: We aimed to investigate whether peripheral blood biomarkers B2M related to immune response can serve as indicators of HAPE pathophysiological characteristics or disease progression.Patients and Methods: Bioinformatics technology was used to explore the peripheral blood pathophysiological mechanisms and immune hub genes related to the occurrence of HAPE. The hub gene was verified through animal experiments, and its function and correlation between its expression level and the diagnosis, treatment effect and prognosis of HAPE were explored.Results: The GSVA results showed that the occurrence of HAPE was related to the down-regulation of immune response pathways by RUNX3 and STING. WGCNA results showed that the peripheral blood immune gene module related to the development of HAPE was related to the decrease of immune function and the increase of immune checkpoint molecule PD-L1 gene expression, and the expression of immune checkpoint genes LILRB2 and SIGLEC15 increased. Cytoscape software, RT-qPCR and WB confirmed that the hub gene B2M is a specific peripheral blood biomarker of HAPE. ROC, DCA, RT-qPCR, HE and Masson results showed that the expression of peripheral blood B2M has the ability to indicate the diagnosis, treatment effect and prognosis of HAPE. The decreased expression of B2M protein in peripheral blood leukocytes may be a marker of HAPE. Single-gene GSEA confirmed that the reduced expression of B2M in peripheral blood may be involved in the down-regulation of the antigen presentation pathway mediated by MHC class I molecules, was positively correlated with the down-regulation of the TNF signaling pathway, and was negatively correlated with the expression of LILRB2 and SIGLEC15.Conclusion: The occurrence of HAPE may be related to decreased immune function and immune tolerance. Peripheral blood B2M may be involved in the related pathways, its expression level can prompt the diagnosis, treatment and prognosis of HAPE. Keywords: high altitude pulmonary edema, immune tolerance, biomarker, B2M, prognosis

Keywords

• high altitude pulmonary edema
• immune tolerance
• biomarker
• b2m
• prognosis