{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T02:20:54Z","timestamp":1794018054686,"version":"4.8.0"},"reference-count":33,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Predominantly antibody deficiencies (PAD) represent the most common type of primary immunodeficiencies in humans, characterized by a wide variation in disease onset, clinical manifestations, and outcome. Considering that the prevalence of PAD in Greece is unknown, and there is limited knowledge on the clinical and laboratory characteristics of affected patients, we conducted a nationwide study. Materials and Methods: 153 patients (male\/female: 66\/87; median age: 43.0 years; range: 7.0\u201377.0) diagnosed, and followed-up between August 1979 to September 2023. Furthermore, we classified our cohort into five groups according to their medical history, immunoglobulin levels, and CTLA4-mutational status: 123 had common variable immunodeficiency (CVID), 12 patients with \u201csecondary\u201d hypogammaglobulinemia due to a previous B-cell depletion immunotherapy for autoimmune or malignant disease several years ago (median: 9 years, range 6\u201314) displaying a typical CVID phenotype, 7 with combined IgA and IgG subclass deficiencies, 5 patients with CVID-like disease due to CTLA4-mediated immune dysregulation syndrome, and 6 patients with unclassified hypogammaglobulinemia. Results: We demonstrated a remarkable delay in PAD diagnosis, several years after the onset of related symptoms (median: 9.0 years, range: 0\u201343.0). A family history of PAD was only present in 11.8%, with the majority of patients considered sporadic cases. Most patients were diagnosed in the context of a diagnostic work-up for recurrent infections, or recurrent\/resistant autoimmune cytopenias. Interestingly, 10 patients (5.6%) had no history of infection, diagnosed due to either recurrent\/resistant autoimmunity, or during a work-up of their medical\/family history. Remarkable findings included an increased prevalence of lymphoproliferation (60.1%), while 39 patients (25.5%) developed bronchiectasis, and 16 (10.5%) granulomatous disease. Cancer was a common complication in our cohort (25 patients, 16.3%), with B-cell malignancies representing the most common neoplasms (56.7%). Conclusion: Our findings indicate the necessity of awareness about PAD and their complications, aiming for early diagnosis and the appropriate management of affected patients.<\/jats:p>","DOI":"10.3390\/medicina60050782","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T13:20:24Z","timestamp":1715174424000},"page":"782","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Nationwide Study of the Delayed Diagnosis and the Clinical Manifestations of Predominantly Antibody Deficiencies and CTLA4-Mediated Immune Dysregulation Syndrome in Greece"],"prefix":"10.3390","volume":"60","author":[{"given":"Androniki","family":"Kapousouzi","sequence":"first","affiliation":[{"name":"Department of Immunology and Histocompatibility, Faculty of Medicine, University of Thessaly, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fani","family":"Kalala","sequence":"additional","affiliation":[{"name":"Department of Immunology and Histocompatibility, Faculty of Medicine, University of Thessaly, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8134-9228","authenticated-orcid":false,"given":"Styliani","family":"Sarrou","sequence":"additional","affiliation":[{"name":"Department of Immunology and Histocompatibility, Faculty of Medicine, University of Thessaly, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5132-8255","authenticated-orcid":false,"given":"Evangelia","family":"Farmaki","sequence":"additional","affiliation":[{"name":"Pediatric Immunology and Rheumatology Referral Center, First Department of Pediatrics, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Antonakos","sequence":"additional","affiliation":[{"name":"4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Kakkas","sequence":"additional","affiliation":[{"name":"Department of Immunology and Histocompatibility Department, \u201cEvaggelismos\u201d General Hospital, 10676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Kourakli","sequence":"additional","affiliation":[{"name":"Hematology Division, Department of Internal Medicine, University of Patras Medical School-University Hospital, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassiliki","family":"Labropoulou","sequence":"additional","affiliation":[{"name":"Hematology Division, Department of Internal Medicine, University of Patras Medical School-University Hospital, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charikleia","family":"Kelaidi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology-Oncology (T.A.O.), \u201cAghia Sophia\u201d Children\u2019s Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Tsiouma","sequence":"additional","affiliation":[{"name":"ENT Department, General Hospital of Volos, 38222 Volos, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Dimou","sequence":"additional","affiliation":[{"name":"Department of Haematology and Bone Marrow Transplantation, \u201cLaikon\u201d General Hospital, National and Kapodistrian University of Athens, 15772 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8766-1853","authenticated-orcid":false,"given":"Theodoros P.","family":"Vassilakopoulos","sequence":"additional","affiliation":[{"name":"Department of Haematology and Bone Marrow Transplantation, \u201cLaikon\u201d General Hospital, National and Kapodistrian University of Athens, 15772 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Voulgarelis","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, \u201cLaikon\u201d General Hospital, Medical School, National University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilias","family":"Onoufriadis","sequence":"additional","affiliation":[{"name":"Department of Immunology and Histocompatibility, Faculty of Medicine, University of Thessaly, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Papadimitriou","sequence":"additional","affiliation":[{"name":"Pediatric Immunology and Rheumatology Referral Center, First Department of Pediatrics, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Polychronopoulou","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology-Oncology (T.A.O.), \u201cAghia Sophia\u201d Children\u2019s Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4713-3911","authenticated-orcid":false,"given":"Evangelos J.","family":"Giamarellos-Bourboulis","sequence":"additional","affiliation":[{"name":"4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3685-3473","authenticated-orcid":false,"given":"Argiris","family":"Symeonidis","sequence":"additional","affiliation":[{"name":"Hematology Division, Department of Internal Medicine, University of Patras Medical School-University Hospital, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4769-8376","authenticated-orcid":false,"given":"Christos","family":"Hadjichristodoulou","sequence":"additional","affiliation":[{"name":"Laboratory of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 41222 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3315-6947","authenticated-orcid":false,"given":"Anastasios E.","family":"Germenis","sequence":"additional","affiliation":[{"name":"Department of Immunology and Histocompatibility, Faculty of Medicine, University of Thessaly, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1287-7734","authenticated-orcid":false,"given":"Matthaios","family":"Speletas","sequence":"additional","affiliation":[{"name":"Department of Immunology and Histocompatibility, Faculty of Medicine, University of Thessaly, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1007\/s10875-022-01352-z","article-title":"The 2022 Update of IUIS Phenotypical Classification for Human Inborn Errors of Immunity","volume":"42","author":"Bousfiha","year":"2022","journal-title":"J. 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