{"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=GSE333202"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Coexistent alterations of BAFF and B cell phenotypes in complicated CVID course","description":"Background: Common variable immunodeficiency (CVID) is a primary immunodeficiency marked by impaired antibody production and infection susceptibility, with about half developing non-infectious complications. BAFF elevation and genetic variants in a BAFF receptor, transmembrane activator and CAML interactor (TACI), frequently occur in CVID. While these findings associate with autoimmune and lymphoproliferative complications, pathogenic mechanisms remain incompletely defined. Objective: This work explored how coexistent changes in BAFF, its receptors, and B cell subsets may shape CVID. Methods: Plasma protein measurement, spectral flow cytometry, and single-cell RNA sequencing was applied. Results: CVID with autoimmune cytopenias and lymphoid hyperplasia had elevated plasma BAFF:TACI ratio and increased transitional and activated naïve B cells. Activated naïve B cells from CVID patients had increased mRNA of genes downstream of BAFF receptor (BAFF-R) that promote B cell survival. Also on these expanded subsets, BAFF-R surface protein decreased, consistent with negative feedback, while autoreactive B cell receptor (BCR) VH4-34 clonality increased. Conclusions: Novel application of spectral flow cytometry, paired BCR sequencing RNA-seq, and measurement of BAFF and related proteins in plasma found CVID with autoimmune and lymphoproliferative complications to be marked by coexistent BAFF and B cell subset dysregulation. This included increased plasma BAFF, BAFF:TACI ratio, and transitional and activated naïve B cells with reduced BAFF-R expression and BCR repertoire diversity. The expanded activated naïve B cell subset in CVID had increased expression of BAFF-R-driven genes that subvert B cell tolerance as well as increased autoreactive VH4-34 clonality. Convergence of BAFF, its receptors, and B cell subset dysregulation, should be further explored in CVID.","dates":{"publication":"2026/05/29"},"accession":"GSE333202","cross_references":{"GSM":["GSM9758937","GSM9758915","GSM9758936","GSM9758914","GSM9758935","GSM9758934","GSM9758919","GSM9758918","GSM9758917","GSM9758939","GSM9758938","GSM9758916","GSM9758933","GSM9758932","GSM9758931","GSM9758930","GSM9758926","GSM9758948","GSM9758947","GSM9758925","GSM9758946","GSM9758924","GSM9758923","GSM9758945","GSM9758929","GSM9758928","GSM9758949","GSM9758927","GSM9758940","GSM9758944","GSM9758922","GSM9758943","GSM9758921","GSM9758920","GSM9758942","GSM9758941"],"GPL":["30173"],"GSE":["333202"],"taxon":["Homo sapiens"]}}