Biology subjects

Nerviani, A.

Publications and source records attributed to Nerviani, A..

3 recordsLinked to original sources

bioRxiv2026

Molecular and spatial profiling identifies immune endotypes for the stratification of OA patients

Osteoarthritis (OA) is a prevalent and heterogeneous joint disease in which synovial inflammation drives structural progression and pain. Despite the recognized heterogeneity of OA, the cellular and molecular organization of synovial tissue remains poorly characterized and defining distinct histological and immune endotypes could guide precision medicine and therapeutic targeting. We show that histologically defined synovial pathotypes are conserved across independent cohorts and correspond to distinct molecular immune endotypes. Integration of bulk and spatial transcriptomics with proteomics revealed niche-specific gene and protein signatures, reflecting the anatomical and functional diversity of OA synovium. The lympho-myeloid pathotype was characterized by mature ectopic lymphoid structures containing CD21+CD23+ follicular dendritic cells, spatially organized T and B cell zones, and clonally expanded T and B cells with shared immune cell receptor motifs, consistent with local adaptive immune activity correlating with radiological joint damage. These findings highlight how immune organization and cellular composition shape OA pathogenesis and provide a framework for endotype-guided stratification and therapeutic targeting.

immunology↗

bioRxiv2023

Spatial mapping of rheumatoid arthritis synovial niches reveals specific macrophage networks associated with response to therapy

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease affecting peripheral joints and for which approximately 40% of the patients respond insufficiently to the available synthetic or biologic disease modifying anti-rheumatic drugs (DMARDs). The infiltration of the synovial membrane by lymphocytes and monocytes profoundly alters its homeostatic functions, leading to chronic joint inflammation and bone destruction. A better understanding of how DMARDs impact the complex synovial cell social network in relationship to response/ non-response remains an unmet need to design more targeted and active therapeutic strategies. Here, we used imaging mass cytometry (IMC) to comparatively profile more than 115,000 cells in the synovial tissue of healthy, low inflammatory osteoarthritis and matched active early treatment-naive RA patients at baseline and at 6 months after starting DMARDs treatment. We notably highlighted that tissue resident macrophages (LYVE1+CD206+) in perivascular synovial niches encompassing specific subsets of vascular cells, fibroblasts and immune cells vanished in active RA but were recovered in response to DMARDs treatment. Combined ligand-receptor analysis of single-cell RNA sequencing datasets identified that IL10, C-type lectin or TAM (TYRO3, AXL and MERTK) receptors were particularly involved in the restoration of these spatial cell interactions in the context of clinical remission. In addition to providing an unprecedented synovial spatial mapping, our work uncovered novel potential cellular and molecular targets for the development of therapies for RA. One Sentence SummarySingle-cell spatial profiling of rheumatoid arthritis synovium identifies specific cell states linked to treatment response

immunology↗

bioRxiv2022

Cellular deconstruction of inflamed synovium defines diverse inflammatory phenotypes in rheumatoid arthritis

Rheumatoid arthritis (RA) is a prototypical autoimmune disease that causes destructive tissue inflammation in joints and elsewhere. Clinical challenges in RA include the empirical selection of drugs to treat patients, inadequate responders with incomplete disease remission, and lack of a cure. We profiled the full spectrum of cells in inflamed synovium from patients with RA with the goal of deconstructing the cell states and pathways characterizing pathogenic heterogeneity in RA. Our multicenter consortium effort used multi-modal CITE-seq, RNA-seq, and histology of synovial tissue from 79 donors to build a >314,000 single-cell RA synovial cell atlas with 77 cell states from T, B/plasma, natural killer, myeloid, stromal, and endothelial cells. We stratified tissue samples into six distinct cell type abundance phenotypes (CTAPs) individually enriched for specific cell states. These CTAPs demonstrate the striking diversity of RA synovial inflammation, ranging from marked enrichment of T and B cells (CTAP-TB) to a congregation of specific myeloid, fibroblast, and endothelial cells largely lacking lymphocytes (CTAP-EFM). Disease-relevant cytokines, histology, and serology metrics are associated with certain CTAPs. This comprehensive RA synovial atlas and molecular, tissue-based CTAP stratification reveal new insights into RA pathology and heterogeneity, which could lead to novel targeted-treatment approaches in RA.

genomics↗