Impact Factor 5.511

Among the world's top 10 most-cited Immunology journals

This article is part of the Research Topic

Human Disorders of PI3K Biology

Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2018.02172

Class-switch recombination (CSR)/Hyper-IgM (HIGM) syndrome and Phosphoinositide 3-kinase (PI3K) defects

 Rekha Jhamnani1, 2, Cristiane Nunes-Santos3,  Jenna Bergerson2 and  Sergio Rosenzweig4*
  • 1Allergy & Immunology fellowship program, National Institute of Allergy and Infectious Diseases (NIAID), United States
  • 2Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), United States
  • 3Immunology Service, DLM, NIH Clinical Center (CC), United States
  • 4Laboratory of Host Defenses, National Institutes of Health (NIH), United States

Antibody production and function represent an essential part of the immune response, particularly in fighting bacterial and viral infections. Multiple immunological phenotypes can result in dysregulation of the immune system humoral compartment, including class-switched recombination (CSR) defects associated with hyper-IgM (HIGM) syndromes. The CSR/HIGM syndromes are defined by the presence of normal or elevated plasma IgM levels in the context of low levels of switched IgG, IgA, and IgE isotypes. Recently described autosomal dominant gain-of-function (GOF) mutations in PIK3CD and PIK3R1 cause combined immunodeficiencies that can also present as CSR/HIGM defects. These defects, their pathophysiology and derived clinical manifestations are described in depth. Previously reported forms of CSR/HIGM syndromes are briefly reviewed and compared to the phosphoinositide 3-kinase (PI3K) pathway defects. Diseases involving the PI3K pathway represent a distinctive subset of CSR/HIGM syndromes, presenting with their own characteristic clinical and laboratory attributes as well as individual therapeutic approaches.

Keywords: Class-switched recombination, somatic hypermutation, CD40L/CD40 pathway, NF-kB pathway, mTOR pathway, Gain of function mutations, PIK3CD, PIK3R1

Received: 05 Feb 2018; Accepted: 03 Sep 2018.

Edited by:

Stuart G. Tangye, Garvan Institute of Medical Research, Australia

Reviewed by:

Klaus Warnatz, Albert-Ludwigs-Universität Freiburg, Germany
Mike Recher, Universität Basel, Switzerland  

Copyright: © 2018 Jhamnani, Nunes-Santos, Bergerson and Rosenzweig. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Sergio Rosenzweig, National Institutes of Health (NIH), Laboratory of Host Defenses, Bethesda, 20892, MD, United States,