{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T20:57:53Z","timestamp":1790456273702,"version":"4.1.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100022965","name":"Ministerio de Ciencia, Tecnolog\u00eda e Innovaci\u00f3n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100022965","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Despite the widespread use of antiretroviral therapy (ART), people\u00a0living with HIV continue to exhibit persistent immune alterations. Among the most affected cell populations are B lymphocytes, which show disruptions in differentiation, class-switch recombination, and the development of immunological memory. However, the relationship between these abnormalities, Epstein\u2013Barr virus (EBV) coinfection, and clinical outcomes across different stages of HIV disease remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed 272 patients living with HIV from Hospital Universitario San\u00a0Ignacio (Bogot\u00e1, Colombia), divided in four groups: clinical stage (S1, S2, S3 and lymphoma), clinical categories: AIDS-defining diseases, non-AIDS-defining diseases, and coinfections (CI), time on ART (&amp;lt;1 year, &amp;gt;1 year); and EBV coinfection. B lymphocyte subpopulations and immunoglobulin isotypes were quantified (next-generation flow cytometry). Cytokines (multiplex assays) and EBV viral load (quantitative PCR) were measured.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HIV progression was observed, associated with B cell compartment remodeling, characterized by depletion of na\u00efve and memory B cells (smIgA1\u20132 and smIgG1\u20134) and an increase in immature\/transitional cells and alterations in smIgM with isotype switching. These variations correlated negatively with clinical stage (\u03c1 up to \u20130\u00b743). The cytokine profile showed a persistent inflammatory signature (MIP-1\u03b2, G-CSF, FLT-3L, and IL-3). EBV coinfection intensified this phenotype, being associated with elevated levels of IL-6, IL-10, IL-15, TNF-\u03b1, and sCD40L, and with greater loss of memory cell subpopulations. Patients with AIDS-defining diseases and lymphomas exhibited the most profound alteration. Even after prolonged ART (&amp;gt;1 year), B cell reconstitution remained incomplete and biased toward immature phenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study shows that recovery of the B cell compartment under ART is incomplete and functionally unbalanced. Humoral memory loss, bias toward immature phenotypes, and persistent inflammation create a state of dysregulation that is exacerbated by EBV coinfection, especially in advanced clinical stages. These immunological defects provide a basis for the pathogenesis of non-AIDS-defining diseases and Epstein-Barr-associated lymphomas. Our findings support the need to integrate advanced immunological assessments, including standardized flow cytometry, as a complement to CD4+ count and viral load, in order to more accurately characterize immune competence and anticipate clinical risks in people living with HIV.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1791480","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T05:35:52Z","timestamp":1773812152000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Incomplete B-cell reconstitution in ART-treated people living with HIV is associated with EBV-linked lymphoma progression"],"prefix":"10.3389","volume":"17","author":[{"given":"Niyireth","family":"Pe\u00f1aloza","sequence":"first","affiliation":[{"name":"Grupo de Inmunobiolog\u00eda y Biolog\u00eda Celular, Pontificia Universidad Javeriana","place":["Bogot\u00e1, Colombia"]},{"name":"Grupo de 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