Complement System in the Pathogenesis of Benign Lymphoepithelial Lesions of the Lacrimal Gland

Abstract

ObjectiveWe aimed to examine the potential involvement of local complement system gene expression in the pathogenesis of benign lymphoepithelial lesions (BLEL) of the lacrimal gland.MethodsWe collected data from 9 consecutive pathologically confirmed patients with BLEL of the lacrimal gland and 9 cases with orbital cavernous hemangioma as a control group, and adopted whole genome microarray to screen complement system-related differential genes, followed by RT-PCR verification and in-depth enrichment analysis (Gene Ontology analysis) of the gene sets.ResultsThe expression of 14 complement system-related genes in the pathologic tissue, including C2, C3, ITGB2, CR2, C1QB, CR1, ITGAX, CFP, C1QA, C4B|C4A, FANCA, C1QC, C3AR1 and CFHR4, were significantly upregulated while 7 other complement system-related genes, C5, CFI, CFHR1|CFH, CFH, CD55, CR1L and CFD were significantly downregulated in the lacrimal glands of BLEL patients. The microarray results were consistent with RT-PCR analysis results. Immunohistochemistry analysis of C3c and C1q complement component proteins in the resected tissue were positive in BLEL patients, while the control group had negative expression of these proteins. Gene ontology (GO) analysis revealed that activation of the genes of complement system-mediated signaling pathways were the most enriched differential gene group in BLEL patients.ConclusionsLocal expression of complement components is prominently abnormal in BLEL, and may well play a role in its pathogenesis.

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

“…This study had some limitations and the role of the mannosebinding lectin pathway in the pathogenesis of LGBLEL was not veri ed. Due to the di culty in obtaining normal lacrimal gland tissue, orbital CH was used as the control group, in line with previous studies [10] . In conclusion, the results of this and of previous studies indicate that both the classical pathway of the complement system and the bypass alternative pathway are involved in the pathogenesis of LGBLEL.…”

“…Previous studies used transcriptomics to preliminarily determine the involvement of the complement system in the pathogenesis of LGBLEL [10] . Transcriptomics analyzes organisms at the transcriptional level, including the regulation and function of genes at different stages of disease, while proteomics is a comprehensive and in-depth study of the proteome of disease and is used to screen key protein biomarkers.…”

“…LGBLEL through transcriptome sequencing and revealed a relationship between the complement system and the pathogenesis of LGBLEL [10] . On this basis, the current study intends to further examine the role of the complement system in LGBLEL through proteomics.…”

Macrophage migration inhibitory factor contributes to the pathogenesis of benign lymphoepithelial lesion of the lacrimal gland

“…By analyzing the gene expression profile between Cavernous Hemangioma (CH), a benign, non-infiltrative, slowly progressive vascular neoplasm of the orbit [ 30 , 31 ] and BLEL, some authors reported the involvement of T-cell receptor (TCR)-signaling pathway [ 32 ], Complement System [ 33 ] and B-cell receptor signaling pathways in the pathogenesis of BLEL [ 34 , 35 ], that confirmed the role played by the inflammatory process in the pathogenesis of BLEL. Here, we sought to identify the mediators of the inflammatory response and highlight their implication in the pathogenesis of the disease.…”

The Involvement of the Fcεri Signaling Pathway in the Pathogenesis of Lacrimal Gland Benign Lymphoepithelial Lesions

“…Studies have found that complement mediated signaling pathways, T cell signaling pathways, and B cell signaling pathways are all involved in the pathogenesis of LGBLEL [1,7,8] . FcεRI is a high-affinity IgE receptor, which has been shown to be involved in type I hypersensitivities, such as allergic asthma [9] .…”