Purpose: Our understanding of the inborn errors of immunity that cause immunodeficiencies is increasing however, their contribution to pediatric sepsis is unknown.
Methods: We used whole exome sequencing to characterize variants previously reported in monogenic immunologic disorders in 330 children admitted to intensive care for severe sepsis. Candidate variants were restricted to novel null variants or rare variants classified as pathogenic or potentially pathogenic in Qiagen’s Human Genetic Mutation Database in a disease consistent inheritance pattern.
Results: One in two children overall and two of three African American children had immunodeficiency-associated variants. Children with candidate variants had increased odds of isolating a blood or urinary pathogen (blood: OR 2.05, 95% CI 1.16 - 3.65, p- value = 0.014, urine: OR: 2.35, 95% CI 1.02 – 5.41, p- value = 0.04) and laboratory evidence of increased immune activation with increased odds of hyperferritinemia (ferritin ≥ 500 ng/ml, OR: 1.92, 95% CI: 1.16 – 3.20, p- value = 0.013) and lymphopenia (minimum lymphocyte count <1000/µL, OR: 1.62, 95% CI: 1.03 – 2.55, p- value = 0.038).
Conclusion: Herein, we describe the genetic findings in this pediatric sepsis cohort and their microbiologic and immunologic significance providing rationale for screening children with life-threatening infection for potential inborn errors of immunity.