Advances in diagnosis of inborn errors of immunity (IEI) and an understanding of the molecular and immunologic mechanisms of these disorders have led to both the development of new therapies and improved approaches to hematopoietic cell transplantation (HCT). For example, monoclonal antibodies (mAbs) and small molecules, such as Janus tyrosine kinase inhibitors, that can modulate immunologic pathways have been designed for or repurposed for management of IEI. A better understanding of molecular mechanisms of IEI has led to use of drugs typically considered “immunosuppressive” to modulate the immune response, such as mammalian target of rapamycin inhibitors in disorders of phosphoinositide 3-kinase gain of function. Since the first HCT in a patient with severe combined immunodeficiency (SCID) in 1968, transplantation strategies have improved, with more than 90% probability of survival after allogeneic HCT in SCID and hence HCT is now the therapeutic standard for SCID and many other IEI. When tailoring treatment for IEI, multiple disease-specific and individual factors should be considered. In diseases such as SCID or agammaglobulinemia, the choice between HCT or medical management is straightforward. However, in many IEI, the choice between the options is challenging. This review focuses on the factors that should be taken into account in the quest for the optimal treatment for patients with IEI.

Original languageEnglish
Pages (from-to)628-639
Number of pages12
JournalJournal of Allergy and Clinical Immunology: In Practice
Issue number2
StatePublished - Feb 2021


  • Gene therapy
  • Hematopoietic cell therapy
  • Immune dysregulation
  • Inborn errors of immunity


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