BACKGROUND: Acinetobacter baumannii is a critical global health threat due to multidrug resistance and high mortality. Although antimicrobial resistance mechanisms are well characterised, the virulence determinants that drive severe infections remain poorly understood. METHODS: We screened 89 carbapenem-resistant clinical isolates of A. baumannii for virulence in animal infection models and combined comparative genomics with functional assays to identify virulence factors. An immunoglobulin-binding protein from A. baumannii (ImbA) encoded on the type D plasmid was selected and characterised. Protein-immunoglobulin interactions were analysed by pull-down and biolayer interferometry. Additional ImbA inhibition of IgG-Fcγ receptor binding by flow cytometry were tested. Protective efficacy was evaluated in mice using vaccination or anti-ImbA antibodies. FINDINGS: A type D plasmid was consistently linked to high virulence in clinical isolates. The deletion of plasmid-encoded ImbA attenuated virulence. ImbA bound murine IgA and IgG with high affinity. The binding to the Fc region of IgG disrupted IgG-Fcγ receptor interactions. Vaccination with recombinant ImbA improved survival and reduced bacterial dissemination in female mice with anti-ImbA antibodies partially protecting against lethal infection. Bacterial burdens in the blood were reduced in treated groups. INTERPRETATION: Our study demonstrates ImbA as an unrecognised plasmid-encoded virulence factor in A. baumannii. By intercepting host immunoglobulins, ImbA drives immune evasion and hypervirulence. Blocking ImbA by vaccination and antibody therapy restored host defence and improved outcomes in female mice, highlighting ImbA as a non-antibiotic therapeutic target with potential against multidrug-resistant A. baumannii. FUNDING: Bio&Medical Technology Development Program of the National Research Foundation (NRF), funded by the Korean government (MSIT) (No. RS-2023-00219213); Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program.

OBJECTIVE: Cardiovascular disease in SLE is not fully explained by traditional risk factors, supporting a role for disease-specific immunovascular mechanisms. Autoantibodies targeting endothelin receptor A (ETAR) and endothelin receptor B (ETBR) have been implicated in vascular injury in other autoimmune diseases, but their clinical and functional relevance in SLE remains unclear. We tested whether ET receptor autoantibodies associate with endothelial activation and directly stimulate ET receptor signalling in SLE. METHODS: Plasma anti-ETAR and anti-ETBR autoantibodies and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured in a pilot cohort of women with SLE and non-SLE controls and in an independent validation cohort stratified by SLE and hypertension (HTN) status. Multivariable models adjusted for demographic variables, blood pressure and medication use. Mechanistic studies were performed in primary human renal endothelial cells (HRECs) using live-cell calcium (Ca2+) imaging, ET receptor antagonists and receptor-directed blocking peptides. RESULTS: Anti-ETAR and anti-ETBR autoantibodies were elevated in SLE across both cohorts, with the highest level observed in SLE with HTN. Anti-ETAR demonstrated the strongest association with sVCAM-1 and independently identified women with the highest endothelial activation burden beyond clinical covariates and anti-double-stranded DNA. In primary HRECs, SLE-derived IgG induced Ca2+ flux that was attenuated by ET receptor antagonism. Blockade of the ETAR extracellular loop 2 domain reduced IgG-mediated Ca2+signalling, supporting a non-canonical mechanism of endothelial ETAR activation. CONCLUSIONS: Anti-ETAR autoantibodies associate with immunovascular risk and endothelial activation in SLE and directly stimulate endothelial signalling through a non-canonical ETAR-dependent mechanism. These findings support the use of anti-ETAR autoantibodies as clinically relevant biomarkers and potential novel contributors to vascular dysfunction in SLE.

Mare endometrosis is a chronic degenerative condition of the endometrium, primarily characterized by fibrosis, involving interactions among fibroblasts, immune cells, and epithelial cells regulated by cytokines and growth factors. T helper (Th)1 and Th2 cells seem to play a pivotal role in fibrosis. However, their roles in equine endometrial fibrosis remain unknown. This study explores Th1 and Th2 cell distribution across different stages of endometrium histopathological Kenney and Doig categories; and evaluated their secretome effects on non-fibrotic endometrium derived fibroblast functional characteristics, extracellular matrix (ECM)-associated mRNA transcription, and transcriptomic profiles. Th1 and Th2 cells, along with cytokines (IFN-γ, IL-4, IL-13) and their receptors, were present in mare endometria at all endometrium stages. Th1 secretome influenced genes enriched in metabolism, cell cycle, and ECM-related pathways, while Th2 secretome regulated genes enriched in tissue remodeling and signaling pathways, suggesting their role in the development of fibrosis in the endometrosis progression.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-20152-0.