Combined immunodeficiencies

J Pediatr (Rio J). 2021 Mar-Apr;97 Suppl 1(Suppl 1):S39-S48. doi: 10.1016/j.jped.2020.10.014. Epub 2020 Dec 17.


Objectives: Inborn Errors of Immunity (IEI), also known as primary immunodeficiencies, correspond to a heterogeneous group of congenital diseases that primarily affect immune response components. The main clinical manifestations comprise increased susceptibility to infections, autoimmunity, inflammation, allergies and malignancies. The aim of this article is to review the literature on combined immunodeficiencies (CIDs) focusing on the diagnosis and treatment and the particularities of the clinical management of these patients.

Source of data: Critical integrative review, aimed to present articles related to primary immunodeficiencies combined with a searchin the PubMed and SciELO databases, with evaluation of publications from the last twenty years that were essential for the construction of knowledge on this group of diseases.

Summary of data: We highlight the main characteristics of CIDs, dividing them according to their pathophysiological mechanisms, such as defects in the development of T cells, TCR signaling, co-stimulatory pathways, cytokine signaling, adhesion, migration and organization of the cytoskeleton, apoptosis pathways, DNA replication and repair and metabolic pathways. In CIDs, clinical manifestations vary widely, from sinopulmonary bacterial infections and diarrhea to opportunistic infections, caused by mycobacteria and fungi. Neonatal screening makes it possible to suspect these diseases before clinical manifestations appear.

Conclusions: The CIDs or IEI constitute a complex group of genetic diseases with T-cell involvement. Neonatal screening for these diseases has improved the prognosis of these patients, especially in severe ones, known as SCIDs.

Keywords: Gene therapy; Hematopoietic stem cell transplantation; Immunosuppression; Molecular biology; Primary immunodeficiency; Vaccination.

Publication types

  • Review

MeSH terms

  • Humans
  • Immunologic Deficiency Syndromes* / diagnosis
  • Infant, Newborn
  • Neonatal Screening
  • Severe Combined Immunodeficiency*
  • T-Lymphocytes