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

Front. Pediatr. | doi: 10.3389/fped.2019.00353

Inborn errors of immunity with immune dysregulation: from bench to bedside

  • 1National Institutes of Health (NIH), United States
  • 2Division of Intramural Research, National Institute of Allergy and Infectious Diseases, United States
  • 3Department of Pediatrics, San Matteo Hospital Foundation (IRCCS), Italy
  • 4Angelo Nocivelli Institute for Molecular Medicine, Department of Molecular and Translational Medicine, University of Brescia, Italy

Primary immune deficiencies (PIDs) are genetic disorders with broad clinical manifestations, ranging from increased susceptibility to infections to significant immune dysregulation, often leading to multiple autoimmune phenomena, lymphoproliferation and malignancy. The treatment is challenging as it requires careful balancing of immunosuppression in subjects at increased risk of infections. Recently, the improved ability to define PID pathophysiology at the molecular level has set the basis for the development of targeted therapeutic interventions. Such a “precision medicine” approach is mainly bases on the use of available small molecules and biologics to target a specific cell function. In this article, we summarize the clinical and laboratory features of various recently described PIDs associated with immune dysregulation and hyperinflammation and present mechanism-based therapeutic approaches that have been implemented in these disorders.

Keywords: primary immunodeficiency diseases (PID) - , immunedysregulation - , Combined immune deficiency, precision medicine, small molecules –, monoclonals –, gain of function (GOF)

Received: 08 May 2019; Accepted: 08 Aug 2019.

Copyright: © 2019 Delmonte, Castagnoli, Calzoni and Notarangelo. 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. Luigi D. Notarangelo, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Bethesda, United States,