{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:50:29Z","timestamp":1787946629297,"version":"build-2784847793"},"reference-count":102,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T00:00:00Z","timestamp":1695859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency. CVID is a heterogeneous disorder with a presumed multifactorial etiology. Intravenous or subcutaneous immunoglobulin replacement therapy (IgRT) can prevent severe infections but not underlying immune dysregulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we evaluated the serum concentrations of proinflammatory (TNF-\u03b1, IL-1\u03b2, IL-6) and immunoregulatory cytokines (IL-10), as well as lipopolysaccharide (LPS) and soluble CD14 (sCD14) in CVID individuals with infectious only (INF-CVID), and those with additional systemic autoimmune and inflammatory disorders (NIC-CVID), and healthy donors (HD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results showed increased serum concentrations of TNF-\u03b1, IL-1\u03b2, IL-6, and IL-10 in both INF-CVID and NIC-CVID subjects compared to HD. However, elevations of TNF-\u03b1, IL-1\u03b2, IL-6, and IL-10 were significantly more marked in NIC-CVID than INF-CVID. Additionally, LPS concentrations were increased only in NIC-CVID but not in INF-CVID compared to HD. Circulating levels of sCD14 were significantly increased in NIC-CVID compared to both INF-CVID and HD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings indicate persistent cytokine dysregulation despite IgRT in individuals with CVID. Moreover, the circulating cytokine profile reveals the heterogeneity of immune dysregulation in different subgroups of CVID subjects.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1257398","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T04:03:37Z","timestamp":1695960217000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Cytokine dysregulation despite immunoglobulin replacement therapy in common variable immunodeficiency (CVID)"],"prefix":"10.3389","volume":"14","author":[{"given":"Remo","family":"Poto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Pecoraro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne 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