Characteristics of Serum Autoantibody Repertoire and Immune Subgroup Variation of Tuberculosis-Associated Obstructive Pulmonary Disease

Abstract

Min Jiang,1,* NanNan Pang,2,* Jing Wang,1 Zheng Li,1 Dan Xu,1 Jing Jing,1 Dan Chen,3 Fengsen Li,1 Jianbing Ding,4 Qifeng Li5 1Xinjiang Key Laboratory of Respiratory Disease Research, Traditional Chinese Medical Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830011, Xinjiang, People’s Republic of China; 2CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, People’s Republic of China; 3School of Public Health, Xinjiang Medical University, Urumqi, 830017, Xinjiang, People’s Republic of China; 4Department of Immunology, College of Basic Medicine, Xinjiang Medical University, Urumqi, 830011, Xinjiang, People’s Republic of China; 5Xinjiang Institute of Pediatrics, Xinjiang Hospital of Beijing Children’s Hospital, Children’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830011, Xinjiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qifeng Li, Xinjiang Institute of Pediatrics, Xinjiang Hospital of Beijing Children’s Hospital, Children’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830054, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected]: Studying the potential etiology and pathogenesis of tuberculosis-associated chronic obstructive pulmonary disease (TOPD) from an autoimmunity perspective may provide insights into peripheral blood autoantibodies and immune cells, as well as their interactions.Methods: This study examined the serum autoantibody repertoire in healthy individuals, patients with chronic obstructive pulmonary disease (COPD), patients with pulmonary tuberculosis (TB), and TOPD patients using the HuProtTM protein chip. Autoantigens in the peripheral blood of TOPD patients were verified using ELISA assay. Various epitopes and immune simulation were predicted using bioinformatic methods. Flow cytometry was employed to detect macrophages(M&phis;), T cells, and innate lymphoid cells (ILCs) in the peripheral blood.Results: COPD patients displayed distinct alterations in their IgG and IgM autoantibodies compared to the other groups. GeneOntology (GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses revealed that these autoantibodies were associated with regulating macrophages, T cells, and B cells. ELISA results confirmed the upregulation of expression of proliferating cell nuclear antigen (PCNA), Mitogen-Activated Protein Kinase 3 antigen (MAPK3), and threonine protein kinase 1 antigen (AKT1) proteins in the peripheral blood of TOPD patients. Bioinformatic analysis predicted multiple potential epitopes in Th, CTL, and B cells. Immune simulation results demonstrated that PCNA, MAPK3, and AKT1 can activate innate and adaptive immune responses and induce the expression of different cytokines, such as IFN-g and IL-2. Furthermore, data obtained from flow cytometry assay revealed an upregulation in the face of Th1 cells in the peripheral blood of TOPD patients.Conclusion: Tuberculosis infection can effectively induce autoimmune responses, contributing to increased expression of Th1 cells and associated cytokines, ultimately leading to immune dysregulation. Furthermore, the accumulation of pulmonary inflammatory response facilitates the progression of TOPD and is helpful for the clinical diagnosis and the development of targeted therapeutic drugs for this disease.Keywords: chronic obstructive pulmonary disease, COPD, autoantibody, autoimmunity, inflammatory phenotype

Keywords

• chronic obstructive pulmonary disease ;copd
• autoantibody
• autoimmunity
• inflammatory phenotype.