POS1407 TOLL-LIKE RECEPTORS SIGNATURE IN ACTIVE LUPUS NEPHRITIS
Authors: M. Dudkova, A. Petrackova, M. Skacelova, J. Videman, V. Smotkova Kraiczova, R. Nesnadna, M. Kudelka, A. Smrzova, A. Skoumalova, E. Kriegova, P. Horak
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The role of innate immunity in systemic lupus erythematosus (SLE) development is already known, but the expression of TLRs might vary in different clinical manifestations of the disease. Only little is known about the expression of TLRs in lupus nephritis (LN). Our study investigated the expression of the m-RNA of Toll-like receptor (TLRs) family as part of the innate gene signature in the clinically defined group of SLE patients with and without the lupus nephritis and assessed their potential for diagnosing organ involvement or damage. <h3>Objectives:</h3> To determine the differences in the TLRs gene expression signature in systemic lupus erythematosus (SLE) patients with/ without LN and in healthy controls. <h3>Methods:</h3> The TLR1-10 m-RNA expression was investigated in peripheral blood mononuclear cells from SLE patients (n=74) and healthy controls (n=34). We compared the subgroup of patients with histologically confirmed active lupus nephritis, defined as renal SLEDAI ≥4 (n=13), with non-LN patients. The expression of TLRs m-RNA was performed by RT-qPCR using high-throughput SmartChip Real-Time-qPCR system (WaferGen). Disease activity was evaluated by SLEDAI and damage by SLICC scores. Statistical analysis (Mann-Whitney, U test, regression analysis) were used to evaluate the obtained results. <h3>Results:</h3> Analysis revealed an upregulation of TLR4 and TLR10 in SLE patients compared to healthy controls (p=0.01, p=0.0007). The active LN group differed from the non-LN group by higher expression of TLR1 (p=0.03), TLR2 (p=0.07), TLR6 (p=0.05) and TLR8 (p=0.03). The expression of TLR2 ant TLR4 correlated with SLE disease activity assessed by SLEDAI (p≤0.05) in lupus group as a whole.. On the other site, no correlation was found with the SLICC index. Multiple correlations were present between the expression of individual TLRs in the whole lupus cohort: TLR1 correlated with TLR2, TLR4, TLR7, TLR8, and TLR10; TLR2 in addition correlated with TLR 3, TLR5 and TLR8; TLR3 to TLR5; TLR 4 to TLR6, TLR7, TLR8; TLR6 to TLR8 and TLR9, TLLR 7 to TLR8 and TLR10 and TLR8 to TLR10. <h3>Conclusion:</h3> Signature of lupus with LN is characteristic by upregulated TLR1, TLR2, TLR6 and TLR8. The multiple mutual relations of TLRs and their correlation with disease activity demonstrate the activation of innate immunity in SLE and promising targets for future therapies. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> Supported by MH CZ – DRO (FNOl, 00098892) and by IGA_LF_2023_002. <h3>Disclosure of Interests:</h3> Marketa Dudkova: None declared, Anna Petrackova: None declared, Martina Skacelova ELI-Lilly, Novartis, Abbvie, Sobi, UCB, Jakub Videman: None declared, Veronika Smotkova Kraiczova: None declared, Romana Nesnadna: None declared, Milos Kudelka: None declared, Andrea Smrzova: None declared, Adela Skoumalova: None declared, Eva Kriegova: None declared, Pavel Horak ELI-Lilly, Novartis, Abbvie, Sobi, AstraZeneca, Boehringer, UCB, Sandoz, Zentiva, ELI-Lilly, Novartis, Abbvie, Sobi, AstraZeneca, Boehringer, UCB.