Distinctive Tissue and Serum MicroRNA Profile of IgG4-Related Ophthalmic Disease and MALT Lymphoma

Abstract

The molecular pathogenesis of orbital lymphoproliferative disorders, such as immunoglobulin G4-related ophthalmic disease (IgG4-ROD) and orbital mucosa-associated lymphoid tissue (MALT) lymphoma, remains essentially unknown. Differentiation between the two disorders, which is important since the work-up and treatment can vary greatly, is often challenging due to the lack of specific biomarkers. Although miRNAs play an important role in the regulation of carcinogenesis and inflammation, the relationship between miRNA and orbital lymphoproliferative diseases remains unknown. We performed a comprehensive analysis of 2565 miRNAs from biopsy and serum specimens of 17 cases with IgG4-ROD, where 21 cases with orbital MALT lymphoma were performed. We identified specific miRNA signatures and their miRNA target pathways, as well as the network analysis for IgG4-ROD and orbital MALT lymphoma. Machine-learning analysis identified miR-202-3p and miR-7112-3p as the best discriminators of IgG4-ROD and orbital MALT lymphoma, respectively. Enrichment analyses of biological pathways showed that the longevity-regulating pathway in IgG4-ROD and the mitogen-activated protein kinase (MAPK) signaling pathway in orbital MALT lymphoma was most enriched by target genes of downregulated miRNAs. This is the first evidence of miRNA profiles of biopsy and serum specimens of patients with IgG4-ROD and orbital MALT lymphoma. These data will be useful for developing diagnostic and therapeutic interventions, as well as elucidating the pathogenesis of these disorders.

Systematic Bibliometric and Visualized Analysis of Research Hotspots and Trends on the Application of Artificial Intelligence in Ophthalmic Disease Diagnosis

“…AI is widely used to identify ophthalmic diseases, which is typically based on the analysis of ophthalmic images ( Xu et al, 2021a ; Wan et al, 2021b ; Xu et al, 2021b ). In addition, this research also includes the detection of genes related to ophthalmic diseases ( Saikia and Nirmala, 2022 ), ocular metabolites ( Myer et al, 2020 ), and pathology ocular metabolites ( Nezu et al, 2020 ). Areas of active interest and the research frontiers of AI in ophthalmic disease diagnosis can be identified based on the clustering timeline of emerging keywords and co-cited references.…”

Upregulated Expression of Activation-Induced Cytidine Deaminase in Ocular Adnexal Marginal Zone Lymphoma with IgG4-Positive Cells

“…A study by Kasar et al found AID activity even in indolent chronic lymphocytic leukemia, a disease entity known as one of hematologic malignancies with slower progression whole-genome sequencing [32]. Recently, efforts to reveal genomics and metabolomics profiles of IgG4-ROD and IgG4+ MZL of ocular adnexa are underway to reveal the underlying pathogenesis [21,22]. Given the current results, genomic level assessment and evaluation of AID activity may further help clarify the lymphomagenesis of IgG4+ MZL in the setting of IgG4-ROD.…”

“…We previously proposed that ocular adnexal IgG4+ MZL could arise in association with IgG4-ROD [17]. While some researchers tried to propose underground pathogenesis of IgG4+ MZL emergence in the setting of IgG4-ROD [18][19][20][21][22], the mechanism has been unclear to date.…”