{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T06:42:08Z","timestamp":1772779328830,"version":"3.50.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"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>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the clinical relevance of diagnosing and classifying isolated IgG deficiency and combined IgG\/IgM deficiency separately from CVID.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a retrospective cohort of patients with primary hypogammaglobulinemia, we evaluated and compared the clinical spectrum and immunological findings of patients with CVID, isolated IgG deficiency, and combined IgG\/IgM deficiency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In comparison to CVID, respiratory tract infections and gastrointestinal infections were less common in isolated IgG or combined IgG\/IgM deficiency, while recurrent mucocutaneous herpes simplex virus reactivations were more common. With respect to immune dysregulation, splenomegaly and immune thrombocytopenic purpura were more frequently observed in CVID. Comparison of immunophenotypic data, revealed relatively lower class-switch memory B cell counts in CVID, while patients with IgG deficiency displayed lower transitional B cells. Survival analysis for these cohorts reveals a significant divergence in long-term outcomes, demonstrating that patients with CVID experience markedly lower overall survival rates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Comparison of CVID with isolated IgG deficiency or combined IgG\/IgM deficiency revealed distinct immunophenotypic profiles, differences in both infectious and non-infectious manifestations, and markedly worse clinical outcomes in CVID. These findings suggest that CVID and unclassified antibody deficiencies \u2013 manifesting as isolated IgG deficiency or combined IgG\/IgM deficiency \u2013 occupy different immunological niches. Consequently, our data support maintaining CVID as a distinct diagnostic entity, separate from IgG and IgG\/IgM deficiencies, and highlight the need for tailored diagnostic approaches and follow-up strategies for these different forms of primary antibody deficiency.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1777332","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T05:30:40Z","timestamp":1772775040000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and immunological differentiation of isolated IgG and combined IgG &amp; IgM deficiencies from common variable immunodeficiency"],"prefix":"10.3389","volume":"17","author":[{"given":"Yagmur","family":"Dogru","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Hannover Medical School","place":["Hannover, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faranaz","family":"Atschekzei","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Hannover Medical School","place":["Hannover, Germany"]},{"name":"Hannover Medical School, Cluster of Excellence RESIST (EXC 2155)","place":["Hannover, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damla","family":"Dogru","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Hannover Medical School","place":["Hannover, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Torsten","family":"Witte","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Hannover Medical School","place":["Hannover, Germany"]},{"name":"Hannover Medical School, Cluster of Excellence RESIST (EXC 2155)","place":["Hannover, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgios","family":"Sogkas","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Hannover Medical School","place":["Hannover, Germany"]},{"name":"Hannover Medical School, Cluster of Excellence RESIST (EXC 2155)","place":["Hannover, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3466","article-title":"Primary antibody deficiencies","volume":"13","author":"Durandy","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2025.11.009","article-title":"Current concepts: common variable immunodeficiency","volume":"20","author":"Cunningham-Rundles","year":"2025","journal-title":"Ann Allergy Asthma Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2019.02.004","article-title":"The European society for immunodeficiencies (ESID) registry working definitions for the clinical diagnosis of inborn errors of immunity","volume":"7","author":"Seidel","year":"2019","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1552513","article-title":"Reappraisal of IgG subclass deficiencies: a retrospective comparative cohort study","volume":"16","author":"Dogru","year":"2025","journal-title":"Front Immunol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jaip.2015.07.025","article-title":"International consensus document (ICON): common variable immunodeficiency disorders","volume":"4","author":"Bonilla","year":"2016","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00033","article-title":"The expanding field of secondary antibody deficiency: causes, diagnosis, and management","volume":"10","author":"Patel","year":"2019","journal-title":"Front Immunol"},{"key":"B7","unstructured":"Working Definitions for Clinical Diagnosis of PID"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.742530","article-title":"Common variable immunodeficiency-associated cancers: the role of clinical phenotypes, immunological and genetic factors","volume":"13","author":"Bruns","year":"2022","journal-title":"Front Immunol"},{"key":"B9","unstructured":"Leitlinie \u201cDiagnostik auf Vorliegen eines prim\u00e4ren Immundefekts\u201d"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9041049","article-title":"Peripheral blood lymphocyte phenotype differentiates secondary antibody deficiency in rheumatic disease from primary antibody deficiency","volume":"9","author":"Jablonka","year":"2020","journal-title":"J Clin Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v99.5.1544","article-title":"Severe deficiency of switched memory B cells (CD27(+)IgM(-)IgD(-)) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease","volume":"99","author":"Warnatz","year":"2002","journal-title":"Blood"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1080\/00313020801911470","article-title":"B-cell maturation defects in common variable immunodeficiency and association with clinical features","volume":"40","author":"Berglund","year":"2008","journal-title":"Pathology"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2018.09.006","article-title":"Increase of follicular helper T cells skewed toward a Th1 profile in CVID patients with non-infectious clinical complications","volume":"197","author":"Turpin","year":"2018","journal-title":"Clin Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2011.02609.x","article-title":"Age-matched reference values for B-lymphocyte subpopulations and CVID classifications in children","volume":"74","author":"Schatorj\u00e9","year":"2011","journal-title":"Scand J Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2208","DOI":"10.1016\/j.jaci.2018.02.017","article-title":"Age-associated distribution of normal B-cell and plasma cell subsets in peripheral blood","volume":"141","author":"SBlanco","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-014-0087-3","article-title":"Increased prevalence of gastrointestinal viruses and diminished secretory immunoglobulin a levels in antibody deficiencies","volume":"34","author":"van de Ven","year":"2014","journal-title":"J Clin Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-024-01027-4","article-title":"Role of mucosal IgA antibodies as novel therapies to enhance mucosal barriers","volume":"47","author":"SGao","year":"2024","journal-title":"Semin Immunopathol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2018.12.004","article-title":"Differentiation of common variable immunodeficiency from IgG deficiency","volume":"7","author":"Filion","year":"2019","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B19","doi-asserted-by":"publisher","first-page":"498","DOI":"10.2500\/aap.2025.46.250077","article-title":"Comparative analysis of demographic and clinical features in common variable immunodeficiency and selective immunoglobulin G deficiency","volume":"46","author":"Gerek","year":"2025","journal-title":"Allergy Asthma Proc"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.085076","article-title":"Common variable immunodeficiency and idiopathic primary hypogammaglobulinemia: two different conditions within the same disease spectrum","volume":"98","author":"Driessen","year":"2013","journal-title":"Haematologica"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1586\/eci.09.43","article-title":"Role of B cells in common variable immune deficiency","volume":"5","author":"Ahn","year":"2009","journal-title":"Expert Rev Clin Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202149480","article-title":"Follicular helper T cell signature of replicative exhaustion, apoptosis, and senescence in common variable immunodeficiency","volume":"52","author":"Milardi","year":"2022","journal-title":"Eur J Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1006\/clim.1999.4799","article-title":"Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies)","volume":"93","author":"Conley","year":"1999","journal-title":"Clin Immunol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1016\/j.jaip.2025.03.009","article-title":"Uncovering risk factors of premature mortality in common variable immunodeficiency","volume":"13","author":"Bez","year":"2025","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.02.017","article-title":"Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficiencies","volume":"144","author":"Blanco","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"e20250003","DOI":"10.70962\/jhi.20250003","article-title":"Human inborn errors of immunity: 2024 update on the classification from the International Union of Immunological Societies Expert Committee","volume":"1","author":"Poli","year":"2025","journal-title":"J Hum Immun"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.780134","article-title":"Implementation of early next-generation sequencing for inborn errors of immunity: A prospective observational cohort study of diagnostic yield and clinical implications in dutch genome diagnostic centers","volume":"12","author":"Elsink","year":"2021","journal-title":"Front Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1159\/000519199","article-title":"Diagnostic yield and therapeutic consequences of targeted next-generation sequencing in sporadic primary immunodeficiency","volume":"183","author":"Sogkas","year":"2022","journal-title":"Int Arch Allergy Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2265-1","article-title":"Whole-genome sequencing of a sporadic primary immunodeficiency cohort","volume":"583","author":"Thaventhiran","year":"2020","journal-title":"Nature"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1777332\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T05:30:41Z","timestamp":1772775041000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1777332\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,6]]},"references-count":29,"alternative-id":["10.3389\/fimmu.2026.1777332"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1777332","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,6]]},"article-number":"1777332"}}