Presenter of 1 Presentation
O022 - GLYCANS AS KEY CHECKPOINTS OF SELF-TOLERANCE IN SLE (ID 549)
Abstract
Background and Aims
Systemic Lupus Erythematous (SLE) is a classical autoimmune disease that remains an important clinical challenge both in terms of diagnosis and treatment. Glycosylation, as a cell-, tissue-specific modification is associated with organisms’ evolutionary conservation, representing a distinction factor between self- and non-self. Dysregulation of protein N-glycosylation has been reported by others and us to occur in major diseases such as cancer and autoimmune diseases. In this work we aimed to identify glycosylation alterations in autoimmunity and infection and assess its relationship with pro-inflammatory immune responses.
Methods
A combination of advanced tissue mass spectrometry imaging, in situ glyco-characterization and ex vivoglycophenotyping of human kidney biopsies were performed to structurally map the N-glycans repertoire in Lupus Nephritis (LN) samples. In the context of infection, we have glycophenotyped T cells from SARS-CoV-2-infected individuals by FACS.
Results
Interestingly, LN revealed a unique glycan signature characterized by an increased abundance of unusual mannose-enriched glycans that are typically found in lower microorganisms; this glycosignature was specific of LN and has shown to predict the development of chronic kidney disease (CKD) with 93% of specificity. Moreover, this phenotype was associated with increased frequency of a specific T cell subset, equipped with glycan-recognizing receptor, DC-SIGN. Finally, in an in vitro setup, we have observed that this T cell subset is able to sense mannosylated-antigens, leading to its pathogenic activation.
Conclusions
Taken together, this work revealed a unique immunological mechanism based in mannosylated antigens/T-cells/IL-17a axis in SLE immunopathogenesis, proposing glycans as a key target in the comprehension of autoimmunity and infection.