Identifying TNF and IL6 as potential hub genes and targeted drugs associated with scleritis: A bio-informative report

Abstract

BackgroundScleritis is a serious inflammatory eye disease that can lead to blindness. The etiology and pathogenesis of scleritis remain unclear, and increasing evidence indicates that some specific genes and proteins are involved. This study aimed to identify pivotal genes and drug targets for scleritis, thus providing new directions for the treatment of this disease.MethodsWe screened candidate genes and proteins associated with scleritis by text-mining the PubMed database using Python, and assessed their functions by using the DAVID database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to identify the functional enrichment of these genes and proteins. Then, the hub genes were identified with CytoHubba and assessed by protein-protein interaction (PPI) network analysis. And the serum from patients with active scleritis and healthy subjects were used for the validation of hub genes. Finally, the DGIdb database was used to predict targeted drugs for the hub genes for treating scleritis.ResultsA total of 56 genes and proteins were found to be linked to scleritis, and 65 significantly altered pathways were identified in the KEGG analysis (FDR < 0.05). Most of the top five pathways involved the categories “Rheumatoid arthritis,” “Inflammatory bowel disease”, “Type I diabetes mellitus,” and “Graft-versus-host disease”. TNF and IL6 were considered to be the top 2 hub genes through CytoHubba. Based on our serum samples, hub genes are expressed at high levels in active scleritis. Five scleritis-targeting drugs were found among 88 identified drugs.ConclusionsThis study provides key genes and drug targets related to scleritis through bioinformatics analysis. TNF and IL6 are considered key mediators and possible drug targets of scleritis. Five drug candidates may play an important role in the diagnosis and treatment of scleritis in the future, which is worthy of the further experimental and clinical study.

Ophthalmological Manifestations in Inflammatory Bowel Diseases: Keep an Eye on It

“…IL-22 typically protects against bacterial and fungal infections, but recent findings suggest that it amplifies the effects of other cytokines that are known to be involved in ocular inflammation, such as interleukin 1-β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and IL-17. Additionally, elevated levels of IL-22 were detected in patients with scleritis and episcleritis [42,44].…”

“…The inflammation is mediated by the activation of resident immunity cells releasing cytokines and inducing vasodilation with vessels' engorgement [42]. De la Maza et al reported a potential role of interleukin-22 (IL-22) in the pathogenesis of episcleritis and scleritis [43,44]. IL-22 typically protects against bacterial and fungal infections, but recent findings suggest that it amplifies the effects of other cytokines that are known to be involved in ocular inflammation, such as interleukin 1-β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and IL-17.…”

Augenbeteiligung bei ausgewählten rheumatischen Erkrankungen – Klinik im Erwachsenenalter

“…Neben den konventionellen synthetischen (insbesondere MTX) werden die biologischen (z. B. Anti-IL-6, Anti-TNF) [14] oder Targeted Synthetic DMARDs (ts; Tofacitinib, Baricitinib) wegen des schnellen Wirkungseintritts und der guten Verträglichkeit zunehmend favorisiert [15]. Bei besonders schwerem Verlauf von RA und Skleritis (insbesondere mit Nekrose) können Rituximab (Anti-CD-20-Antikörper) [16] oder kombiniert Cyclophosphamid-Puls und Plasmapherese angezeigt sein.…”

“…In the case of a recurrent or particularly severe disease course with the occurrence of secondary complications threatening visual acuity (e.g., ulcerative keratitis, exudative retinal detachment), an interdisciplinary decision must be made on the use or intensification of treatment with DMARDs. In addition to conventional synthetic DMARDs (in particular MTX), biological (e.g., anti-IL-6, anti-TNF) [14] or targeted synthetic (ts) (tofacitinib, baricitinib) DMARDs are increasingly favored because of their rapid effect and good tolerability [15]. In particularly severe courses of RA and scleritis (especially with necrosis), rituximab (anti-CD-20 antibody) [16] or combined pulse cyclophosphamide and plasmapheresis may be indicated.…”