POS0419 ABERRANT SPLICEOSOME AND ALTERED EXPRESSION OF IFN-RESPONSE RELATED GENES ARE HALLMARKS OF MONOCYTES FROM LUPUS PATIENTS WITH RENAL DISEASE

Background: To date, novel mechanisms such as the involvement of splicing machinery components in lupus nephropathy and its interplay with transcriptome innate immune cells have not been evaluated. Objectives: 1- identify altered transcriptomic signatures associated response monocytes from SLE patients association clinical features. 2- evaluate role spliceosome linked to profile monocytes. 3- analyze mechanistically impact anti-dsDNA antibodies (Ab) modulation activity. Methods: Sixty forty healthy donors (HD) were included study. Infiltration rate myeloid features analyzed kidney biopsies by Immunohistochemistry. In parallel, circulating purified peripheral blood immune-magnetic selection. The expression a set 770 genes related autoimmune/inflammatory diseases was evaluated using NanoString Technologies. levels main 45 further these samples microfluidic qPCR array (Fluidigm). An extensive clinical/serological evaluation also performed, comprising disease activity, renal parameters, autoAb profile, systemic inflammatory status (27-plex Assay). Finally, vitro studies involving anti-dsDNA-IgG Ab treatment over/down-expression carried out their effects monocyte Results: CD68 expressing confirmed parameters failure (C3/C4, chronic index), highlighting key compartment nephropathy. Gene profiling recognized 156 differentially expressed compared HDs, including 87 up-regulated 69 down-regulated. Functional analysis showed that most dysregulated IFN (i.e. IFIT1, IFI44, IFI44L, RSAD2). 27 demonstrated HD, 3 24 Correlation aberrant interferon signature plasma profile. This at molecular level activity status, positivity C3/C4 levels. Interestingly, displayed simultaneous alteration both, monocytes, along an enlarged pro-inflammatory plasma. Logistic regression models integrated concomitant some IFNs identified nephritis high accuracy. Mechanistic HDs promoted deregulation several PTB, RBM17, RNU6ATAC). selected (PTB RBM17) reduced active release cytokines adhesion capacity. Conclusion: 1) Monocytes exhibit remarkable response, components. 2) Anti-dsDNA dysregulation both signatures, mediators. 3) reduce migration Ongoing may provide biomarkers therapeutic tools treat Acknowledgements: Funded ISCIII, PI18/00837 RIER RD16/0012/0015 co-funded FEDER Disclosure Interests: None declared