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Purpose: Chronic granulomatous disease (CGD) is an inherited primary immunodeficiency disorder of phagocytes, characterized by recurrent fungal and bacterial infections. Our aim is to describe the different clinical presentations, non-infectious auto-inflammatory features, types and sites of infections, and to estimate the mortality among our large cohort. Methods: This is a retrospective study conducted at the Pediatric Department of Cairo University Children's Hospital in Egypt, including cases with a confirmed CGD diagnosis. Results: One hundred seventy-three confirmed CGD patients were included. AR-CGD was diagnosed in 132 patients (76.3%) including 83 patients (48%) with p47phox defect, 44 patients (25.4%) with p22phox defect, and 5 patients (2.9%) with p67phox defect. XL-CGD was diagnosed in 25 patients (14.4%). The most common recorded clinical manifestations were deep-seated abscesses and pneumonia. Gram-negative bacteria and Aspergillus were the most frequently isolated species. Regarding the outcome, 36 patients (20.8%) were lost from follow-up. Among patients with known outcome, 94/137 patients (68.6%) are living, while 43/137 patients (31.4%) died. Conclusion: AR-CGD is predominant in Egypt; CGD must always be ruled out in any patient presenting with typical or atypical mycobacterial or BCG-disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Human inborn errors of immunity (IEI) are a group of inherited genetic disorders of the immune system. IEI Patients suffer from severe repeated infections, autoimmunity, lymphadenopathy and/or increased susceptibility to malignancies. IEI are due to absence, disproportion, or loss of function of immune cells; mostly inherited in autosomal recessive manner, hence are more common in countries with high rate of consanguinity. Definite diagnosis of IEI is achieved by genetic analysis, however it is not always available. Aim: to report on different IEI categories and impact of expanding the use of flow cytometry (FCM) in diagnosis, categorization and follow up of IEI patients in a highly consanguineous population. Methods: Retrospective chart review on different IEI categories diagnosed at the primary immunodeficiency center in Cairo University Specialized Pediatric hospital from 2011 to 2021 based on expanding the use of FCM. Results: 1510 IEI patients were diagnosed; 480 were diagnosed genetically with FMF, 11 with cystic fibrosis and 1019 patients were diagnosed with other IEI disorders. Phagocytic defects were the commonest (30%) followed by severe combined immunodeficiency (22%) and combined immunodeficiency (18.3%). FCM testing properly diagnosed and categorized 73% of the cases. Conclusion: Using multi-color FCM to evaluate immune cells populations, subpopulations, functions, and intracellular proteins expression is proved a useful cost-effective method for screening, categorization and follow up of IEI patients. FCM can improve the diagnosis of IEI significantly when tests are properly targeted and well designed. This study presents a 10-year experience in diagnosis of IEI using FCM at a tertiary referral center in a setting of limited resources and yet high prevalence of IEI. [ABSTRACT FROM AUTHOR]

Purpose: Leukocyte adhesion deficiency (LAD) represents a rare group of inherited inborn errors of immunity (IEI) characterized by bacterial infections, delayed umbilical stump separation, and autoimmunity. This single-center study aimed at describing the clinical, immunological, and molecular characterizations of 34 LAD-I Egyptian pediatric patients., Methods: Details of 34 patients' personal medical history, clinical and laboratory findings were recorded; Genetic material from 28 patients was studied. Mutational analysis was done by Sanger sequencing., Results: Omphalitis, skin and soft tissue infections with poorly healing ulcers, delayed falling of the umbilical stump, and recurrent or un-resolving pneumonia were the most common presentations, followed by chronic otitis media, enteropathy, periodontitis; and recurrent oral thrush. Persistent leukocytosis and neutrophilia were reported in all patients, as well as CD18 and CD11b deficiency. CD18 expression was < 2% in around 90% of patients. Sixteen different pathological gene variants were detected in 28 patients who underwent ITGß2 gene sequencing, of those, ten were novel and six were previously reported. Three families received a prenatal diagnosis. Patients were on antimicrobials according to culture's results whenever available, and on prophylactic Trimethoprim-Sulfamethoxazole 5 mg/kg once daily, with regular clinical follow up. Hematopoietic stem cell transplantation (HSCT) was offered for 4 patients. However due to severity of the disease and delay in diagnosis, 58% of the patients passed away in the first 2 years of life., Conclusion: This study highlights the importance of early diagnosis and distribution of ITGß2 gene mutation in Egyptian children. Further molecular studies, however, remain a challenging necessity for better disease characterization in the region., (© 2024. The Author(s).)

Background: MHC class II deficiency leads to defective CD4 + T-cell function that results from impaired antigen presentation. A genetic disorder in 1 of 4 genes results in this syndrome that is associated with the clinical phenotype of combined immunodeficiency., Objective: To describe the clinical, immunological, and molecular characteristics of 10 Egyptian patients from 9 different families having presented with MHC class II deficiency between 2012 and 2017., Methods: An initial diagnosis based on the combination of clinical features and low HLA-DR expression by flow cytometry was confirmed by genetic analyses., Results: Symptoms included failure to thrive (n = 9), persistent diarrhea (n = 5), and pneumonia (n = 8). Septicemia due to coagulase-negative staphylococci (n = 1) and Candida krusei (n = 1) was diagnosed. Nine patients orally received the live attenuated polio vaccine, of whom 3 developed acute flaccid paralysis thereafter. Nine patients received the BCG vaccine and none developed obvious signs of BCGitis. Four patients carried RFXANK gene mutations, 3 carried RFX5 gene mutations, 1 carried a CIITA gene mutation, and none carried RFXAP gene mutations. Six of the 7 detected mutations were previously unreported mutations: c.431T>C, c.247&#95;250delTCAG, and c.600delG in the RFXANK gene; c.116+1G>A and c.715C>T in the RFX5 gene; and c.929delA in the CIITA gene., Conclusions: Given that Egypt is a North African country with a high rate of consanguinity, MHC class II deficiency is not rare. However, the molecular defects differ from those reported in nearby countries. Early diagnosis must be based on suspicious clinical signs and laboratory diagnosis because the defect can be missed by T-cell receptor excision circles based on neonatal screening., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

In the past few years, several genes were shown to be implicated in various forms of the Hyper Immunoglobulin E syndrome. The present study is the first to describe a cohort of DOCK8 deficiency patients from Egypt. The study included 15 patients with features of combined immunodeficiency (CID) suggestive of DOCK8 deficiency. Flow cytometry was used for evaluation of DOCK8 expression and studying different immunological characteristics of those patients including evaluation of Th17, Tregs, T and B lymphocytes differentiation and the effect of the DOCK8 deficiency on the activation of the STAT3. Diagnosis was confirmed by mutational analysis. Profound defects in Th17 cells and Tregs were observed in all patients with impaired STAT3 phosphorylation, indicating that DOCK8 plays a pivotal role in the STAT3 signaling pathway. These findings together with decrease in memory B cells and defective DOCK8 expression by flow cytometry can confirm the diagnosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)