The Role of the Complement System Classical and Alternative Pathways in the Pathogenesis of Lacrimal Gland Benign Lymphoepithelial Lesions

Abstract

\n Objective: The complement system plays an important role in chronic inflammation and autoimmune diseases. On the basis of previous studies, this paper further analyzed the role of the complement system classical pathway and alternative pathway in the pathogenesis of lacrimal gland benign lymphoepithelial lesions (LGBLEL).Methods: Six cases of LGBLEL and six cases of orbital cavernous hemangioma (CH), diagnosed by histopathology in Beijing Tongren Hospital, Capital Medical University, between July 2010 and October 2013 were randomly selected for proteomic analysis. Gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to analyze the signaling pathways of differentially expressed genes and proteins. Four LGBLEL and three orbital CH cases, diagnosed by histopathology in Beijing Tongren Hospital, Capital Medical University, between October 2018 and August 2019, were randomly selected as the experimental group and the control group, respectively. RT-PCR, immunohistochemical staining and western blotting were used to verify the genes and proteins related to the complement system signaling pathway.Results: The expression of complement system signaling pathway in LGBLEL tissue was significantly different (P<0.0001) compared with orbital CH, and C3, C5 and C9 were differentially expressed genes. RT-PCR results showed that mRNA expression levels of C1qA, C3, C5 and C9 related to the complement signaling pathway were higher in LGBLEL tissues than in orbital CH (P<0.0001). Immunohistochemical staining results showed that C1qA, C3, C5 and C9 protein expression was significantly higher in LGBLEL tissues than in orbital CH. Western blotting showed that the levels of C1qA, C3, C5 and C9 proteins were significantly higher in LGBLEL tissues than in orbital CH (P=0.0008; P=0.0375; P=0.0306; P=0.0073, respectively).Conclusion: Both the classical and alternative pathways of complement system are involved in the pathogenesis of LGBLEL.