Mortality rate and causes of death in inborn errors of immunity: A systematic review and meta-analysis

Abstract

Background: Patients with inborn errors of immunity (IEI) experience severe infectious and non-infectious complications, leading to an increased risk of mortality. Delayed diagnosis or misdiagnosis significantly contributes to the heightened mortality rates observed in IEI patients. Objectives: This study systematically reviews the causes of mortality in IEI patients with a meta-analysis to determine the mortality rate among patients with various IEI. Methods: Embase, ISI Web of Science, PubMed, and Scopus were searched (up to July 2024) using terms related to IEI and mortality. Results: A total of 12,581 deceased IEI patients were included, with an overall reported mortality rate of 24.0 (95 confidence interval: 23.0-26.0 ) among all published IEI cases. This represents an approximately 27-fold higher mortality rate among IEI patients compared to the mean global mortality rate (24 vs. 0.874 ). Severe combined immunodeficiency, chronic granulomatous disease, and ataxia-telangiectasia had the highest numbers of reported deceased cases (2304, 962, and 820 cases, respectively). However, familial hemophagocytic lymphohistiocytosis exhibited the highest mortality rate (49.0 ). The most common causes of death were infections, transplant-related mortality and non-infectious pulmonary complications, (3429, 2749, and 1141 cases), respectively. Among infectious causes of death, COVID-19 infection accounted for 10.8 (370 cases). Conclusion: This study identifies specific types of IEI with the highest mortality rates and numbers, alongside immune component defects most strongly associated with increased mortality. Patients with immune dysregulation, defects in cellular immunity, and phagocyte function were particularly linked to higher mortality rates, underscoring the urgent need for improved management strategies for these IEIs.