Inborn Errors of Immunity: how to diagnose them?

Grumach, Anete Sevciovic; Goudouris, Ekaterini

doi:10.1016/j.jped.2020.11.007

Cited by 8 publications

(10 citation statements)

References 21 publications

(63 reference statements)

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“…This may be attributed to the lack of a nationwide newborn screening program for IEIs and the highly diverse clinical manifestations of IEIs (related to increased susceptibility to infections, autoimmunity, autoinflammation, allergy, and lymphoproliferative/neoplastic diseases), demanding a high index of suspicion. 17 The diagnosis of IEIs in LMICs is further challenged by low awareness among health care professionals and the public as well as unavailability and high cost of certain diagnostic modalities, particularly molecular testing. 12,13 Having warning signs for IEIs, such as rAOM, could enhance early diagnosis and, consequently, improves patients' outcome.…”

Section: Discussionmentioning

confidence: 99%

“…Findings on clinical evaluation and initial screening tests informed subsequent laboratory investigations. 16 17 18…”

Section: Methodsmentioning

confidence: 99%

“…Findings on clinical evaluation and initial screening tests informed subsequent laboratory investigations. [16][17][18] In brief, a venous blood sample (6 mL) was drawn from each patient under complete aseptic conditions. Two milliliter were gently dispensed into a tube containing K-ethylenediaminetetraacetic acid (1 mg/mL) for CBC with manual differential count using Cell-Dyn 3700 hematology analyzer (Abbot Diagnostics, Abbott Park, IL, United States).…”

Section: Methodsmentioning

confidence: 99%

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Inborn Errors of Immunity among Egyptian Children with Recurrent Acute Otitis Media

Elsameea

Abd-Elkader

Fahmy

et al. 2022

J Pediatr Infect Dis

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Objective Our objective was to investigate the relative frequency and pattern of inborn errors of immunity (IEIs) among Egyptian children with recurrent acute otitis media (rAOM). Methods This was a cross-sectional study that included children from the age of 6 months to 16 years with rAOM. Those with structural, functional, and environmental risk factors were excluded. Enrolled children underwent thorough clinical, otorhinolaryngological, and immunological evaluation, including hematological counting, quantitative immunoglobulins assay, lymphocytic flow cytometric immunophenotyping, CH50, and phagocytic function tests. Results The study included 69 children with rAOM (44 boys and 25 girls; median age 30 months). IEIs were identified in 14 children, including transient hypogammaglobulinemia (three cases), selective IgA deficiency (three cases), agammaglobulinemia (two cases), common variable immunodeficiency (two cases), and one case for each of congenital neutropenia, Chediak–Higashi syndrome, hyper IgM syndrome, and Griscelli syndrome. Parental consanguinity and history of unexplained/infection-related siblings' deaths were significantly associated with IEIs (p = 0.018 and 0.003, respectively). AOM and related complications were more frequent among IEI cases (p = 0.018 and 0.032, respectively). IEI cases had lower levels of hemoglobin (10.7 ± 2.80 vs. 12.3 ± 1.64 g/dL; p = 0.002), IgG (203 [78–1,370] vs. 708 [42.3–1,509] mg/dL; p = 0.000), and IgA (24.3 [3–310] vs. 80 [15.6–305] mg/dL; p = 0.009) compared with non-IEI cases. Conclusion The current study identified IEIs in one-fifth of children with rAOM, most of which were predominately antibody deficiencies. An immunological workup for rAOM is particularly important in the presence of certain indicators for IEIs, provided that other more common risk factors are excluded.

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Section: Discussionmentioning

confidence: 99%

“…Findings on clinical evaluation and initial screening tests informed subsequent laboratory investigations. 16 17 18…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Inborn Errors of Immunity among Egyptian Children with Recurrent Acute Otitis Media

Elsameea

Abd-Elkader

Fahmy

et al. 2022

J Pediatr Infect Dis

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“…Given the substantial overlap in clinical symptomatology between premature infants and those with IEI, we advocate a conservative approach. Many other reviews have covered appropriate testing pathways for a range of IEIs (82)(83)(84). We will summarize briefly here but encourage clinicians to follow standard diagnostic approaches for symptoms that might suggest an IEI.…”

Section: Approaches/solutionsmentioning

confidence: 99%

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

Gordon

O’Connell

2021

Front. Immunol.

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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.

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“…Inborn errors of immunity (IEI) comprise a heterogeneous group of genetic disorders caused by defects in one or more components of the immune system, resulting in a wide spectrum of clinical manifestations and laboratory abnormalities. These patients have an increased susceptibility to infections and higher risks of developing autoimmune diseases and malignancies [ 1 , 2 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic Testing in Egyptian Patients with Inborn Errors of Immunity: a Single-Center Experience

et al. 2022

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Background Inborn errors of immunity (IEI) are a group of heterogeneous disorders with geographic and ethnic diversities. Although IEI are common in Egypt, genetic diagnosis is limited due to financial restrictions. This study aims to characterize the genetic spectrum of IEI patients in Egypt and highlights the adaptation of the molecular diagnostic methods to a resource-limited setting. Methods Genetic material from 504 patients was studied, and proper diagnosis was achieved in 282 patients from 246 families. Mutational analysis was done by Sanger sequencing, next-generation sequencing (NGS) targeting customized genes panels, and whole-exome sequencing (WES) according to the patients’ phenotypes and availability of genetic testing. Results A total of 194 variants involving 72 different genes were detected with RAG1/2 genes being the most encountered followed by DOCK8, CYBA, LRBA, NCF1, and JAK3. Autosomal recessive (AR) inheritance was detected in 233/282 patients (82.6%), X-linked (XL) recessive inheritance in 32/282 patients (11.3%), and autosomal dominant (AD) inheritance in 18/282 patients (6.4%), reflecting the impact of consanguineous marriages on the prevalence of different modes of inheritance and the distribution of the various IEI disorders. Conclusion The study showed that a combination of Sanger sequencing in selected patients associated with targeted NGS or WES in other patients is an effective diagnostic strategy for IEI diagnosis in countries with limited diagnostic resources. Molecular testing can be used to validate other nonexpensive laboratory techniques that help to reach definitive diagnosis and help in genetic counseling and taking proper therapeutic decisions including stem cell transplantation or gene therapy.

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Inborn Errors of Immunity: how to diagnose them?

Cited by 8 publications

References 21 publications

Inborn Errors of Immunity among Egyptian Children with Recurrent Acute Otitis Media

Inborn Errors of Immunity among Egyptian Children with Recurrent Acute Otitis Media

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

Genetic Testing in Egyptian Patients with Inborn Errors of Immunity: a Single-Center Experience

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