{"database":"GEO","file_versions":[],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330223"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Convergence of cytokine dysregulation and antibody deficiency in common variable immunodeficiency with inflammatory complications","description":"Background: Noninfectious complications are the greatest cause of morbidity and mortality in common variable immunodeficiency (CVID), but their pathogenesis remains poorly defined. Objective: Using high-throughput approaches, we aimed to identify, correlate, and determine the significance of immunologic features of CVID with noninfectious complications (CVIDc). Methods: We simultaneously applied proteomics, RNA sequencing, and mass cytometry to a large cohort with primary antibody deficiency. Results: CVIDc is differentiated from uncomplicated CVID, other forms of primary antibody deficiency, and healthy controls by a distinct plasma proteomic profile. In addition to confirming previously reported elevations of 4-1BB, IL-6, IL-18, and IFN-γ, we found elevations of colony-stimulating factor 1, IL-12p40, IL-18R, oncostatin M, TNF, and vascular endothelial growth factor A to differentiate CVIDc. This cytokine dysregulation correlated with deficiency of LPS-specific antibodies and increased soluble CD14, suggesting microbial translocation. Indicating potential significance of reduced LPS-specific antibodies and resultant microbial-induced inflammation, CVIDc had altered LPS-induced gene expression matching plasma proteomics and corresponding with increased CD14+CD16- monocytes, memory T cells, and tissue inflammation ameliorated by T-cell-targeted therapy. Unsupervised machine learning accurately differentiated subjects with CVIDc and supported cytokine dysregulation, antibody deficit, and T-cell activation as defining and convergent features. Conclusions: Our data expand understanding of CVIDc proteomics, establish its link with deficiency of IgA and LPS-specific antibodies, and implicate altered LPS-induced gene expression and elevated monocytes and T cells in this cytokine dysregulation. This work indicates that CVIDc results when insufficient antibody neutralization of pathogen-associated molecular patterns, like LPS, occurs in those with a heightened response to these inflammatory mediators, suggesting a 2-hit model of pathogenesis requiring further exploration.","dates":{"publication":"2026/05/12"},"accession":"GSE330223","cross_references":{"GSM":["GSM9721549","GSM9721569","GSM9721547","GSM9721548","GSM9721567","GSM9721545","GSM9721546","GSM9721568","GSM9721543","GSM9721565","GSM9721566","GSM9721544","GSM9721563","GSM9721541","GSM9721564","GSM9721542","GSM9721561","GSM9721540","GSM9721562","GSM9721560","GSM9721538","GSM9721539","GSM9721558","GSM9721536","GSM9721537","GSM9721559","GSM9721556","GSM9721535","GSM9721557","GSM9721576","GSM9721554","GSM9721555","GSM9721552","GSM9721574","GSM9721575","GSM9721553","GSM9721572","GSM9721550","GSM9721573","GSM9721551","GSM9721570","GSM9721571"],"GPL":["30173"],"GSE":["330223"],"taxon":["Homo sapiens"]}}