Selective IgG4 deficiency and autoimmune cytopenias

Aim: Autoimmune cytopenias are disorders driven by immune-mediated destruction of hematopoietic cells. Recent studies have linked these conditions to inborn errors of immunity (IEI), particularly in patients with recurrent and/or chronic forms. Common variable immunodeficiency (CVID) is the most com...

Full description

Saved in:
Bibliographic Details
Main Authors: Maria Loutsou, Nikolaos Giannakoulas, Emmanouel Ηatzipantelis, Helen Pergantou, Athina Dettoraki, Vasiliki Antari, Aikaterini Michalopoulou, George Vassilopoulos, Styliani Sarrou, Vasiliki Kalaitzidou, Christos Hadjichristodoulou, Fani Kalala, Matthaios Speletas
Format: Article
Language:English
Published: Open Exploration Publishing Inc. 2025-08-01
Series:Exploration of Immunology
Subjects:
Online Access:https://www.explorationpub.com/uploads/Article/A1003207/1003207.pdf
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850043825727209472
author Maria Loutsou
Nikolaos Giannakoulas
Emmanouel Ηatzipantelis
Helen Pergantou
Athina Dettoraki
Vasiliki Antari
Aikaterini Michalopoulou
George Vassilopoulos
Styliani Sarrou
Vasiliki Kalaitzidou
Christos Hadjichristodoulou
Fani Kalala
Matthaios Speletas
author_facet Maria Loutsou
Nikolaos Giannakoulas
Emmanouel Ηatzipantelis
Helen Pergantou
Athina Dettoraki
Vasiliki Antari
Aikaterini Michalopoulou
George Vassilopoulos
Styliani Sarrou
Vasiliki Kalaitzidou
Christos Hadjichristodoulou
Fani Kalala
Matthaios Speletas
author_sort Maria Loutsou
collection DOAJ
description Aim: Autoimmune cytopenias are disorders driven by immune-mediated destruction of hematopoietic cells. Recent studies have linked these conditions to inborn errors of immunity (IEI), particularly in patients with recurrent and/or chronic forms. Common variable immunodeficiency (CVID) is the most common IEI in humans, and autoimmune cytopenias represent the most prevalent autoimmune manifestations of the disease. TNFRSF13B/TACI alterations are the most common genetic defects in CVID patients. The aim of this study was to investigate both the incidence of hypogammaglobulinemia—including immunoglobulin subclass deficiencies—in patients with autoimmune cytopenias, as well as possible correlations with common TNFRSF13B/TACI defects in selective patients. Methods: A cohort of 123 patients (110 adults and 13 children, male/female: 58/65, median age at diagnosis: 50.0 years, range: 1.5–87.0) with autoimmune cytopenias [113 with autoimmune thrombocytopenia (AIT), 8 with autoimmune hemolytic anemia (AHA), and 2 with Evans syndrome] were enrolled in the study. The main immunoglobulin types (IgG, IgM, and IgA) were measured in all patients, while serum for the estimation of IgG subclass levels was available in 84 patients. Genetic analysis of TNFRSF13B/TACI was performed by PCR and Sanger sequencing. Results: Although no deficiency of main immunoglobulin types was detected in any patient, 8 of 84 patients (9.5%) displayed selective IgG4 deficiency (sIgG4D). Among them, three suffered from acute/newly diagnosed AIT, three from chronic AIT, and two from AHA. Interestingly, two patients with sIgG4D exhibited a family history of IEI. Furthermore, one patient (12.5%) carried a pathogenic missense mutation (c.542C>A, p.A181E, rs72553883) in a heterozygous state, while the remaining patients carried only common polymorphisms. Conclusions: IgG4 could be considered a useful biomarker in patients with autoimmune cytopenias, while further studies may elucidate its precise role in disease pathogenesis and prognosis.
format Article
id doaj-art-579448f1623c4a73bccec9dfdd14baf3
institution DOAJ
issn 2768-6655
language English
publishDate 2025-08-01
publisher Open Exploration Publishing Inc.
record_format Article
series Exploration of Immunology
spelling doaj-art-579448f1623c4a73bccec9dfdd14baf32025-08-20T02:55:07ZengOpen Exploration Publishing Inc.Exploration of Immunology2768-66552025-08-015100320710.37349/ei.2025.1003207Selective IgG4 deficiency and autoimmune cytopeniasMaria Loutsou0https://orcid.org/0000-0002-2754-9891Nikolaos Giannakoulas1https://orcid.org/0009-0003-3482-4286Emmanouel Ηatzipantelis2https://orcid.org/0000-0002-7535-2970Helen Pergantou3https://orcid.org/0000-0002-1792-0597Athina Dettoraki4https://orcid.org/0000-0001-8232-3767Vasiliki Antari5Aikaterini Michalopoulou6https://orcid.org/0000-0001-7865-9823George Vassilopoulos7https://orcid.org/0000-0003-4744-7486Styliani Sarrou8https://orcid.org/0000-0001-8134-9228Vasiliki Kalaitzidou9Christos Hadjichristodoulou10https://orcid.org/0000-0002-4769-8376Fani Kalala11https://orcid.org/0009-0001-5588-8014Matthaios Speletas12https://orcid.org/0000-0003-1287-7734Department of Immunology & Histocompatibility, Faculty of Medicine, University of Thessaly, 41500 Larissa, GreeceHematology Department, University Hospital of Thessaly, 41500 Larissa, GreeceChildhood & Adolescent Hematology Oncology Unit, 2nd Pediatric Department, School of Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, GreeceHemophilia Center and Hemostasis and Thrombosis Unit, Agia Sophia Children’s Hospital, 11527 Athens, GreeceHemophilia Center and Hemostasis and Thrombosis Unit, Agia Sophia Children’s Hospital, 11527 Athens, GreeceChildhood & Adolescent Hematology Oncology Unit, 2nd Pediatric Department, School of Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, GreeceHemophilia Center and Hemostasis and Thrombosis Unit, Agia Sophia Children’s Hospital, 11527 Athens, GreeceHematology Department, University Hospital of Thessaly, 41500 Larissa, GreeceDepartment of Immunology & Histocompatibility, Faculty of Medicine, University of Thessaly, 41500 Larissa, GreeceDepartment of Hematology, Papageorgiou General Hospital, 56403 Thessaloniki, GreeceLaboratory of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 41222 Larissa, GreeceDepartment of Immunology & Histocompatibility, Faculty of Medicine, University of Thessaly, 41500 Larissa, GreeceDepartment of Immunology & Histocompatibility, Faculty of Medicine, University of Thessaly, 41500 Larissa, GreeceAim: Autoimmune cytopenias are disorders driven by immune-mediated destruction of hematopoietic cells. Recent studies have linked these conditions to inborn errors of immunity (IEI), particularly in patients with recurrent and/or chronic forms. Common variable immunodeficiency (CVID) is the most common IEI in humans, and autoimmune cytopenias represent the most prevalent autoimmune manifestations of the disease. TNFRSF13B/TACI alterations are the most common genetic defects in CVID patients. The aim of this study was to investigate both the incidence of hypogammaglobulinemia—including immunoglobulin subclass deficiencies—in patients with autoimmune cytopenias, as well as possible correlations with common TNFRSF13B/TACI defects in selective patients. Methods: A cohort of 123 patients (110 adults and 13 children, male/female: 58/65, median age at diagnosis: 50.0 years, range: 1.5–87.0) with autoimmune cytopenias [113 with autoimmune thrombocytopenia (AIT), 8 with autoimmune hemolytic anemia (AHA), and 2 with Evans syndrome] were enrolled in the study. The main immunoglobulin types (IgG, IgM, and IgA) were measured in all patients, while serum for the estimation of IgG subclass levels was available in 84 patients. Genetic analysis of TNFRSF13B/TACI was performed by PCR and Sanger sequencing. Results: Although no deficiency of main immunoglobulin types was detected in any patient, 8 of 84 patients (9.5%) displayed selective IgG4 deficiency (sIgG4D). Among them, three suffered from acute/newly diagnosed AIT, three from chronic AIT, and two from AHA. Interestingly, two patients with sIgG4D exhibited a family history of IEI. Furthermore, one patient (12.5%) carried a pathogenic missense mutation (c.542C>A, p.A181E, rs72553883) in a heterozygous state, while the remaining patients carried only common polymorphisms. Conclusions: IgG4 could be considered a useful biomarker in patients with autoimmune cytopenias, while further studies may elucidate its precise role in disease pathogenesis and prognosis.https://www.explorationpub.com/uploads/Article/A1003207/1003207.pdfautoimmune cytopeniasautoimmune thrombocytopeniaautoimmune hemolytic anemiaigg4immunodeficiencytnfrsf13b/taci
spellingShingle Maria Loutsou
Nikolaos Giannakoulas
Emmanouel Ηatzipantelis
Helen Pergantou
Athina Dettoraki
Vasiliki Antari
Aikaterini Michalopoulou
George Vassilopoulos
Styliani Sarrou
Vasiliki Kalaitzidou
Christos Hadjichristodoulou
Fani Kalala
Matthaios Speletas
Selective IgG4 deficiency and autoimmune cytopenias
Exploration of Immunology
autoimmune cytopenias
autoimmune thrombocytopenia
autoimmune hemolytic anemia
igg4
immunodeficiency
tnfrsf13b/taci
title Selective IgG4 deficiency and autoimmune cytopenias
title_full Selective IgG4 deficiency and autoimmune cytopenias
title_fullStr Selective IgG4 deficiency and autoimmune cytopenias
title_full_unstemmed Selective IgG4 deficiency and autoimmune cytopenias
title_short Selective IgG4 deficiency and autoimmune cytopenias
title_sort selective igg4 deficiency and autoimmune cytopenias
topic autoimmune cytopenias
autoimmune thrombocytopenia
autoimmune hemolytic anemia
igg4
immunodeficiency
tnfrsf13b/taci
url https://www.explorationpub.com/uploads/Article/A1003207/1003207.pdf
work_keys_str_mv AT marialoutsou selectiveigg4deficiencyandautoimmunecytopenias
AT nikolaosgiannakoulas selectiveigg4deficiencyandautoimmunecytopenias
AT emmanouelēatzipantelis selectiveigg4deficiencyandautoimmunecytopenias
AT helenpergantou selectiveigg4deficiencyandautoimmunecytopenias
AT athinadettoraki selectiveigg4deficiencyandautoimmunecytopenias
AT vasilikiantari selectiveigg4deficiencyandautoimmunecytopenias
AT aikaterinimichalopoulou selectiveigg4deficiencyandautoimmunecytopenias
AT georgevassilopoulos selectiveigg4deficiencyandautoimmunecytopenias
AT stylianisarrou selectiveigg4deficiencyandautoimmunecytopenias
AT vasilikikalaitzidou selectiveigg4deficiencyandautoimmunecytopenias
AT christoshadjichristodoulou selectiveigg4deficiencyandautoimmunecytopenias
AT fanikalala selectiveigg4deficiencyandautoimmunecytopenias
AT matthaiosspeletas selectiveigg4deficiencyandautoimmunecytopenias