الفهرس | Only 14 pages are availabe for public view |
Abstract Abstract Background:The Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and type I interferon (IFN) pathways are important inflammatory pathways implicated to the end-organ manifestations in Systemic Lupus Erythematosus (SLE), including lupus nephritis (LN). Proteins of the tripartite motif (TRIM) family have recently emerged as potentially important regulators of the innate immune pathways. TRIM8, a member of the TRIM family, is identified as a positive regulator of IFN response. Its dysfunction is linked to cancer, inflammatory processes and autoimmune disorders. The involvement of TRIM8 is fundamentally linked to its participation in the regulation of three pivotal cellular signaling pathways: the p53 tumor suppressor signaling pathway, the NF-κB pathway and Signal Transducer and Activator of Transcription 3 (STAT3) of the Janus kinase (JAK)-STAT pathway. Objectives: To evaluate the expression of TRIM8 gene in SLE patients with Nephritis and its relation to activity of the disease. Patients and methods: A case-control study of 90 subjects, composed of 70 SLE patients with LN-proven biopsy at the Ain Shams University Hospital, where they were further subdivided into 40 active LN patients and 30 non-active LN patients, while the remaining 20 subjects were age- and sex-matched healthy volunteers. Active LN patients were defined by at least 2 of the following items: i) new onset proteinuria > 0.5g/24hr, ii) active urinary sediments, and iii) a renal biopsy showing evidence of active LN.Whole blood samples were collected, and then peripheral blood mononuclear cells (PBMCs) were extracted and analyzed for the expression of the TRIM8 gene using real-time RT-PCR. Results: The Relative quantification (RQ) of TRIM8 mRNA expression was the highest in the active LN group, followed by the non-active LN group and the lowest in the control group with (p<0.001). RQ of TRIM8 mRNA expression showed highly significant diagnostic performance in differentiating the SLE patients group from the control group with cut-off point >1.556 and area under the curve (AUC) (0.998) and significant diagnostic performance in differentiating active LN from non-active LN with cut-off point ≥63.10 and AUC (0.988) (p<0.001). It showed high diagnostic characteristics in diagnosing the active LN from the non-active LN with 97.5% sensitivity and 100 % specificity. Conclusion: TRIM8 gene expression may be significantly correlated with LN activity so they can be used as diagnostic tests of lupus nephritis activity and as potential therapy targets for further studies |