Patterns of Immune Dysregulation in Primary Immunodeficiencies: A Systematic Review

J Allergy Clin Immunol Pract. 2021 Feb;9(2):792-802.e10. doi: 10.1016/j.jaip.2020.10.057. Epub 2020 Nov 11.


Background: Immune dysregulation is as important as susceptibility to infection in defining primary immunodeficiencies (PIDs). Because of the variability and nonspecificity of the symptoms of PIDs, diagnosis can be delayed-especially if a patient presents with immune dysregulation. Diagnosis is then based on certain combinations of symptoms and relies on the clinician's ability to recognize a pattern. So far there is no large report linking patterns of immune dysregulations to the underlying genetic defects.

Objective: To identify immune dysregulatory patterns associated with PIDs and to help clinicians to detect an underlying PID in certain patients with noninfectious inflammatory diseases.

Method: A systematic literature review was performed.

Results: We included 186 articles that reported on n = 745 patients. The most common immune dysregulation category was "autoimmunity" (62%, n = 463), followed by "intestinal disease" (38%, n = 283) and "lymphoproliferation" (36%, n = 268). Most patients (67%) had 1 or more symptoms of immune dysregulation. Autoimmune hemolytic anemia, the most common autoimmune phenotype, was most frequently reported in patients with LPS responsive beige-like anchor protein deficiency (when combined with hypogammaglobulinemia or gastrointestinal symptoms), activation-induced cytidine deaminase deficiency (when combined with autoimmune hepatitis), or RAG1 deficiency (when it was the only symptom of immune dysregulation). Eczema, allergies, and asthma were reported in 34%, 4%, and 4% of the patients, respectively.

Conclusion: Patterns of immune dysregulation may help the physician to recognize specific PIDs. This systematic review provides clinicians with an overview to better assess patients with immune dysregulation.

Keywords: Autoimmunity; Disease pattern; Eczema; Immune dysregulation; Inborn errors of immunity; Inflammation; Primary immunodeficiencies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Autoimmune Diseases*
  • Autoimmunity
  • Gastrointestinal Diseases*
  • Humans
  • Immunologic Deficiency Syndromes* / diagnosis
  • Immunologic Deficiency Syndromes* / genetics
  • Primary Immunodeficiency Diseases*