Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

A Nationwide Study of the Delayed Diagnosis and the Clinical Manifestations of Predominantly Antibody Deficiencies and CTLA4-Mediated Immune Dysregulation Syndrome in Greece

Androniki Kapousouzi
,
Fani Kalala
,
Styliani Sarrou
ORCID logo ,
Evangelia Farmaki
ORCID logo ,
Nikolaos Antonakos
ORCID logo ,
Ioannis Kakkas
,
Alexandra Kourakli
,
Vasiliki Labropoulou
,
Charikleia Kelaidi
ORCID logo ,
Georgia Tsiouma
,
Maria Dimou
ORCID logo ,
Theodoros Vassilakopoulos
,
MICHAEL VOULGARELIS
,
Ilias Onoufriadis
,
Eleni Papadimitriou
,
Sophia Polychronopoulou
,
Evangelos J Giamarellos-Bourboulis
ORCID logo ,
Argiris Symeonidis
ORCID logo ,
Christos Hadjichristodoulou
,
Anastasios E. Germenis
ORCID logo ,
Matthaios Speletas
* ORCID logo
Version 1 : Received: 23 February 2024 / Approved: 26 February 2024 / Online: 26 February 2024 (12:46:08 CET)

How to cite: Kapousouzi, A.; Kalala, F.; Sarrou, S.; Farmaki, E.; Antonakos, N.; Kakkas, I.; Kourakli, A.; Labropoulou, V.; Kelaidi, C.; Tsiouma, G.; Dimou, M.; Vassilakopoulos, T.; VOULGARELIS, M.; Onoufriadis, I.; Papadimitriou, E.; Polychronopoulou, S.; Giamarellos-Bourboulis, E.J.; Symeonidis, A.; Hadjichristodoulou, C.; Germenis, A.E.; Speletas, M. A Nationwide Study of the Delayed Diagnosis and the Clinical Manifestations of Predominantly Antibody Deficiencies and CTLA4-Mediated Immune Dysregulation Syndrome in Greece. Preprints 2024, 2024021425. https://doi.org/10.20944/preprints202402.1425.v1 Kapousouzi, A.; Kalala, F.; Sarrou, S.; Farmaki, E.; Antonakos, N.; Kakkas, I.; Kourakli, A.; Labropoulou, V.; Kelaidi, C.; Tsiouma, G.; Dimou, M.; Vassilakopoulos, T.; VOULGARELIS, M.; Onoufriadis, I.; Papadimitriou, E.; Polychronopoulou, S.; Giamarellos-Bourboulis, E.J.; Symeonidis, A.; Hadjichristodoulou, C.; Germenis, A.E.; Speletas, M. A Nationwide Study of the Delayed Diagnosis and the Clinical Manifestations of Predominantly Antibody Deficiencies and CTLA4-Mediated Immune Dysregulation Syndrome in Greece. Preprints 2024, 2024021425. https://doi.org/10.20944/preprints202402.1425.v1

Abstract

Predominantly antibody deficiencies (PAD) represent the most common type of primary immu-nodeficiencies in humans, characterized by a wide variation in disease onset, clinical manifesta-tions, complications and outcome. Considering that the prevalence of PAD in Greece is unknown and there is limited knowledge on clinical and laboratory characteristics of affected patients, we conducted a nationwide study, including 153 patients (male/female: 66/87; median age: 43.0 years; range: 7.0-77.0) diagnosed and/or followed-up between April 2007 to September 2023. Furthermore, we classified our cohort into five Groups according to their medical history, im-munoglobulin levels, and CTLA4-mutational status: 123 had common variable immunodeficien-cy (CVID), 12 with CVID-like disease (with a history of a previous B-cell depletion immunother-apy for autoimmune or malignant disease), seven with combined IgA and IgG subclass deficien-cies, five with immune dysregulation syndrome and CTLA4 defects, and six with unclassified hypogammaglobulinemia. We demonstrated a remarkable delay of PAD diagnosis, several years after the onset of related symptoms (median: 9.0 years, range: 0-43.0). Family history of PAD was only 11.8%, with the majority of patients considered sporadic cases. Most patients were diag-nosed in the context of a diagnostic work-up for recurrent infections, or recurrent/resistant auto-immune cytopenias. Interestingly, ten 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%) and atopy (24.2%), while 39 patients (25.5%) developed bronchiectasis and 16 (10.5%) granulomatous dis-ease. Patients with CTLA4 defects displayed a variable clinical phenotype at diagnosis, with four patients diagnosed during a work-up of re-current infections, while one also displayed a massive splenomegaly. Cancer was a common complication in our cohort (25 patients, 16.3%), with B-cell malignancies representing the most common neoplasms (56.7%). Our findings indicate the necessity of awareness about PAD and their complications, aiming for early diagnosis and appropriate management of affected patients

Keywords

predominantly antibody deficiencies, common variable immunodeficiency, IgA deficiency, IgG subclass deficiency, CTLA4, diagnosis

Subject

Medicine and Pharmacology, Immunology and Allergy

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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