Patterns of Immune Dysregulation in Primary Immunodeficiencies: A Systematic Review

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