Inborn Errors of Immunity in the Premature Infant: Challenges in Recognition and Diagnosis

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 Jan 10

PMID 35003071

Authors

Scott M Gordon

Amy E OConnell

Affiliations

Soon will be listed here.

Abstract

Due to heightened awareness and advanced genetic tools, inborn errors of immunity (IEI) are increasingly recognized in children. However, diagnosing of IEI in premature infants is challenging and, subsequently, reports of IEI in premature infants remain rare. This review focuses on how common disorders of prematurity, such as sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia, can clinically overlap with presenting signs of IEI. We present four recent cases from a single neonatal intensive care unit that highlight diagnostic dilemmas facing neonatologists and clinical immunologists when considering IEI in preterm infants. Finally, we present a conceptual framework for when to consider IEI in premature infants and a guide to initial workup of premature infants suspected of having IEI.

Citing Articles

Canine Amniotic Fluid at Birth Holds Information about Neonatal Antibody Titres against Core Vaccine Viruses.

Groppetti D, Pecile A, Filipe J, Riva F, Inglesi A, Kuhn P Vet Sci. 2024; 11(6).

PMID: 38921981 PMC: 11209429. DOI: 10.3390/vetsci11060234.

Effects of extremely preterm birth on cytokine and chemokine responses induced by T-cell activation during infancy.

Govindaraj D, Bach Jensen G, Qazi K, Sverremark-Ekstrom E, Abrahamsson T, Jenmalm M Clin Transl Immunology. 2024; 13(5):e1510.

PMID: 38737447 PMC: 11087183. DOI: 10.1002/cti2.1510.

Assessing whole-exome sequencing data from undiagnosed Brazilian patients to improve the diagnostic yield of inborn errors of immunity.

Ferreira C, da Silva Francisco Junior R, Gerber A, Guimaraes A, Amendola F, Pinto-Mariz F BMC Genom Data. 2023; 24(1):36.

PMID: 37391719 PMC: 10314602. DOI: 10.1186/s12863-023-01137-2.

Premature Infants Have Normal Maturation of the T Cell Receptor Repertoire at Term.

Morton S, Schnur M, Kerper R, Young V, OConnell A Front Immunol. 2022; 13:854414.

PMID: 35707545 PMC: 9189380. DOI: 10.3389/fimmu.2022.854414.

Inborn Errors of Immunity With Fetal or Perinatal Clinical Manifestations.

Carneiro-Sampaio M, de Jesus A, Bando S, Moreira-Filho C Front Pediatr. 2022; 10:891343.

PMID: 35601409 PMC: 9121170. DOI: 10.3389/fped.2022.891343.

References

Castagnoli R, Pala F, Bosticardo M, Licari A, Delmonte O, Villa A . Gut Microbiota-Host Interactions in Inborn Errors of Immunity. Int J Mol Sci. 2021; 22(3). PMC: 7866830. DOI: 10.3390/ijms22031416. View

Nogee L, Ryan R . Genetic Testing for Neonatal Respiratory Disease. Children (Basel). 2021; 8(3). PMC: 8001923. DOI: 10.3390/children8030216. View

Williamson S, Rasanayagam C, Glover K, Baptista J, Naik S, Satodia P . Rapid exome sequencing: revolutionises the management of acutely unwell neonates. Eur J Pediatr. 2021; 180(12):3587-3591. PMC: 8212268. DOI: 10.1007/s00431-021-04115-x. View

Swanson J, Gurka M, Kaufman D . Risk Factors for Invasive Fungal Infection in Premature Infants: Enhancing a Targeted Prevention Approach. J Pediatric Infect Dis Soc. 2015; 3(1):49-56. DOI: 10.1093/jpids/pit068. View

Pagel J, Twisselmann N, Rausch T, Waschina S, Hartz A, Steinbeis M . Increased Regulatory T Cells Precede the Development of Bronchopulmonary Dysplasia in Preterm Infants. Front Immunol. 2020; 11:565257. PMC: 7554370. DOI: 10.3389/fimmu.2020.565257. View

Amatuni G, Sciortino S, Currier R, Naides S, Church J, Puck J . Reference intervals for lymphocyte subsets in preterm and term neonates without immune defects. J Allergy Clin Immunol. 2019; 144(6):1674-1683. PMC: 6900445. DOI: 10.1016/j.jaci.2019.05.038. View

Sampath V, Menden H, Helbling D, Li K, Gastonguay A, Ramchandran R . SIGIRR genetic variants in premature infants with necrotizing enterocolitis. Pediatrics. 2015; 135(6):e1530-4. PMC: 4444800. DOI: 10.1542/peds.2014-3386. View

Grumach A, Goudouris E . Inborn Errors of Immunity: how to diagnose them?. J Pediatr (Rio J). 2021; 97 Suppl 1:S84-S90. PMC: 9432000. DOI: 10.1016/j.jped.2020.11.007. View

Kwan A, Puck J . History and current status of newborn screening for severe combined immunodeficiency. Semin Perinatol. 2015; 39(3):194-205. PMC: 4433840. DOI: 10.1053/j.semperi.2015.03.004. View

10.

Reis M, Willis G, Fernandez-Gonzalez A, Yeung V, Taglauer E, Magaletta M . Mesenchymal Stromal Cell-Derived Extracellular Vesicles Restore Thymic Architecture and T Cell Function Disrupted by Neonatal Hyperoxia. Front Immunol. 2021; 12:640595. PMC: 8082426. DOI: 10.3389/fimmu.2021.640595. View

11.

Kumar V, Wang H, Nielsen L . Adaptive immune responses are altered in adult mice following neonatal hyperoxia. Physiol Rep. 2018; 6(2). PMC: 5789729. DOI: 10.14814/phy2.13577. View

12.

Bastarache L, Hughey J, Hebbring S, Marlo J, Zhao W, Ho W . Phenotype risk scores identify patients with unrecognized Mendelian disease patterns. Science. 2018; 359(6381):1233-1239. PMC: 5959723. DOI: 10.1126/science.aal4043. View

13.

Vissing N, Monster M, Nordly S, Dayani G, Heedegaard S, Knudsen J . Relapse of Neonatal Meningitis: Did We Miss Something at First?. Children (Basel). 2021; 8(2). PMC: 7916591. DOI: 10.3390/children8020126. View

14.

Romberg N, Vogel T, Canna S . NLRC4 inflammasomopathies. Curr Opin Allergy Clin Immunol. 2017; 17(6):398-404. PMC: 6070355. DOI: 10.1097/ACI.0000000000000396. View

15.

Canna S, de Jesus A, Gouni S, Brooks S, Marrero B, Liu Y . An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat Genet. 2014; 46(10):1140-6. PMC: 4177369. DOI: 10.1038/ng.3089. View

16.

Delmonte O, Castagnoli R, Calzoni E, Notarangelo L . Inborn Errors of Immunity With Immune Dysregulation: From Bench to Bedside. Front Pediatr. 2019; 7:353. PMC: 6718615. DOI: 10.3389/fped.2019.00353. View

17.

Tangye S, Al-Herz W, Bousfiha A, Chatila T, Cunningham-Rundles C, Etzioni A . Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol. 2020; 40(1):24-64. PMC: 7082301. DOI: 10.1007/s10875-019-00737-x. View

18.

Neu J, Walker W . Necrotizing enterocolitis. N Engl J Med. 2011; 364(3):255-64. PMC: 3628622. DOI: 10.1056/NEJMra1005408. View

19.

Goldbach-Mansky R, Dailey N, Canna S, Gelabert A, Jones J, Rubin B . Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med. 2006; 355(6):581-92. PMC: 4178954. DOI: 10.1056/NEJMoa055137. View

20.

Yu W, Haque I, Venkatraman A, Menden H, Mabry S, Roy B . SIGIRR Mutation in Human Necrotizing Enterocolitis (NEC) Disrupts STAT3-Dependent microRNA Expression in Neonatal Gut. Cell Mol Gastroenterol Hepatol. 2021; 13(2):425-440. PMC: 8688179. DOI: 10.1016/j.jcmgh.2021.09.009. View