Biology subjects

Hurabielle, C.

Publications and source records attributed to Hurabielle, C..

3 recordsLinked to original sources

bioRxiv2026

Longitudinal linear-epitope profiling of SLE identifies novel antigens associated with disease and disease activity

Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disease defined by the production of autoantibodies directed against diverse self-antigens. Antinuclear antibodies (ANA) are central to SLE diagnosis, and anti-double-stranded DNA (anti-dsDNA) antibodies are clinically used to track disease activity. However, these biomarkers provide only partial insight into the full spectrum of autoimmune changes in patients. To expand the known landscape of SLE autoreactivity shared among patients and associated with disease activity, we performed an unbiased characterization of 1,268 SLE plasma samples from 695 SLE patients and 301 healthy controls using phage immunoprecipitation and sequencing (PhIP-seq). This technique preferentially displays linear epitopes, and thus provides a complementary set of autoreactivities to previously discovered autoreactive targets. Despite the marked clinical heterogeneity of SLE, machine learning applied to this data surfaced a shared, reproducible signature that robustly discriminates between SLE and healthy controls in two validation cohorts. Autoreactivities in SLE were significantly enriched for RNA-binding protein targets. Autoreactive proteins containing Basic Acidic Dipeptides (BAD) repeat domains, features associated with biomolecular condensate formation, distinguished patients with high disease activity (by SLEDAI score) from patients with no disease activity. Among all shared autoreactivities, a peptide derived from YTHDF2 emerged as the most prevalent target across SLE cohorts occurring in ~25% of SLE patients and displayed striking sequence similarity to a peptide derived from the Epstein Barr virus (EBV) lytic switch protein BZLF1. Competition assays demonstrated higher-affinity binding to the viral peptide, supporting a model in which antiviral humoral responses to EBV may drive secondary epitope spreading toward molecularly mimicked self-antigens. Remarkably, orthogonal validation using the Luminex bead platform containing a panel of only 10 peptides, including BZLF1, demonstrated strong discrimination between SLE and healthy controls (AUC = 0.95). Together, these findings identify a rich, greatly expanded landscape of autoreactivities in SLE, candidate biomarkers associated with high disease activity, and provide mechanistic insight linking EBV-driven immunity to epitope-specific autoimmunity in lupus.

immunology↗

bioRxiv2025

The emerging fungal pathogen Candida auris induces IFNγ to colonize mammalian hair follicles

Public health alarm concerning the emerging fungus Candida auris is fueled by its antifungal drug resistance and propensity to cause deadly outbreaks. Persistent skin colonization drives transmission and lethal sepsis although its basis remains mysterious. We compared the skin colonization dynamics of C. auris with its relative C. albicans, quantifying skin fungal persistence and distribution and immune composition and positioning. C. auris displayed a higher propensity to colonize hair follicles and avidly bound to human hair. While C. albicans triggered an effective sterilizing type 3/17 antifungal immune response driven by IL-17A/F-producing lymphocytes, C. auris triggered a type 1, IFN{gamma}-driven immune response targeting hair follicles. Rather than promoting fungal clearance, IFN{gamma} enhanced C. auris skin colonization by acting directly on keratinocytes impairing epithelial barrier integrity and repressing antifungal defense programs. C. auris exploits focal skin immune responses to create a niche for persistence in hair follicles.

immunology↗

bioRxiv2019

Decoding commensal-host communication through genetic engineering of Staphylococcus epidermidis

Commensal skin bacteria elicit potent, antigen-specific immune responses in the skin without barrier breach or visible inflammation. While microbial modulation of immune homeostasis has profound consequences for epithelial health and inflammatory skin diseases, the mechanisms of microbe-immune crosstalk in the skin are largely unknown. A key barrier to mechanistic work has been genetic intractability of one of the most prevalent skin colonists, Staphylococcus epidermidis (S. epidermidis). Here, we develop a novel method to create a library of mutants with defined cell envelope alterations in primary human S. epidermidis isolates. By colonizing mice with these mutants, we uncover bacterial molecules involved in the induction of defined immune signatures. Notably, we show that under conditions of physiologic colonization, S. epidermidis cell envelope glycolipids are sensed by C-type lectin receptors, likely in non-myeloid cells, in conjunction with Toll-like receptors. This combinatorial signaling determines the quality of T cell responses and results in the potential for greater specificity toward commensal microbiota than previously appreciated. Additionally, the microbial molecules required for the colonization-induced immune response are dispensable for T cells responses in a model of S. epidermidis infection, but differentially modulate innate inflammatory responses. Thus, the same microbe uses distinct sets of molecules to signal to the immune system commensal versus pathogenic behavior, and differential sensing of these microbial signals depends on host context.

microbiology↗