Next Article in Journal
Real-Life Patterns of Exacerbations While on Inhaled Corticosteroids and Long-Acting Beta Agonists for Asthma over 15 Years
Next Article in Special Issue
The Usefulness of Scintigraphic Studies in the Assessment of Asymptomatic Bowel Disease in Patients with Primary Antibody Diseases
Previous Article in Journal
Evaluation of the Dimensional Accuracy of 3D-Printed Anatomical Mandibular Models Using FFF, SLA, SLS, MJ, and BJ Printing Technology
Previous Article in Special Issue
Chromothripsis and DNA Repair Disorders
Open AccessArticle

Clinical, Immunological, and Functional Characterization of Six Patients with Very High IgM Levels

1
Department of Translational Medical Sciences-Section of Pediatrics, Federico II University, 80131 Naples, Italy
2
Department of Molecular Medicine and Medical Biotechnology, Federico II University, 80131 Naples, Italy
3
Advanced Biotechnologies s.c.a.r.l., CEINGE, 80131 Naples, Italy
4
Department of Clinical Medicine and Surgery-Hematology, Federico II University, 80131 Naples, Italy
5
Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
6
Center for Pediatric Genomic Medicine, Children’s Mercy Hospital, Kansas City, MO 64108, USA
7
Laboratory of Human Lymphohematopoiesis, INSERM UMR U1163 and Paris Descartes—Sorbonne Paris Cité University, Imagine Institute, 75743 Paris, France
8
Pediatric Allergology and Immunology Unit, University of Rome Tor Vergata, Policlinico Tor Vergata, 00133 Rome, Italy
*
Author to whom correspondence should be addressed.
Equally contributing first Authors.
These Authors contributed equally to this work.
J. Clin. Med. 2020, 9(3), 818; https://doi.org/10.3390/jcm9030818
Received: 20 January 2020 / Revised: 3 March 2020 / Accepted: 13 March 2020 / Published: 17 March 2020
(This article belongs to the Special Issue Clinical Research on Primary Immunodeficiency Diseases)
Very high IgM levels represent the hallmark of hyper IgM (HIGM) syndromes, a group of primary immunodeficiencies (PIDs) characterized by susceptibility to infections and malignancies. Other PIDs not fulfilling the diagnostic criteria for HIGM syndromes can also be characterized by high IgM levels and susceptibility to malignancies. The aim of this study is to characterize clinical phenotype, immune impairment, and pathogenic mechanism in six patients with very high IgM levels in whom classical HIGM syndromes were ruled out. The immunological analysis included extended B-cell immunophenotyping, evaluation of class switch recombination and somatic hypermutation, and next generation sequencing (NGS). Recurrent or severe infections and chronic lung changes at the diagnosis were reported in five out of six and two out of six patients, respectively. Five out of six patients showed signs of lymphoproliferation and four patients developed malignancies. Four patients showed impaired B-cell homeostasis. Class switch recombination was functional in vivo in all patients. NGS revealed, in one case, a pathogenic mutation in PIK3R1. In a second case, the ITPKB gene, implicated in B- and T-cell development, survival, and activity was identified as a potential candidate gene. Independent of the genetic basis, very high IgM levels represent a risk factor for the development of recurrent infections leading to chronic lung changes, lymphoproliferation, and high risk of malignancies. View Full-Text
Keywords: hyper IgM syndrome; lymphoproliferative disorders; class switch recombination; somatic hypermutation; DNA repair hyper IgM syndrome; lymphoproliferative disorders; class switch recombination; somatic hypermutation; DNA repair
Show Figures

Figure 1

MDPI and ACS Style

Gallo, V.; Cirillo, E.; Prencipe, R.; Lepore, A.; Del Vecchio, L.; Scalia, G.; Martinelli, V.; Di Matteo, G.; Saunders, C.; Durandy, A.; Moschese, V.; Leonardi, A.; Giardino, G.; Pignata, C. Clinical, Immunological, and Functional Characterization of Six Patients with Very High IgM Levels. J. Clin. Med. 2020, 9, 818.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop