Meshaal, S., R. EI Hawary, D. S. Abd Elaziz, A. Eldash, R. Darwish, A. Erfan, S. Lotfy, M. Saad, E. Chohayeb, M. Nagy, et al., "Clinical and immunological features of four patients with activation-induced cytidine deaminase deficiency: Renal amyloidosis and other presentations", Annals of Human Genetics, 2024.
Chohayeb, E. A., S. Lotfy, R. E. E. Hawary, S. S. Meshaal, I. A. Mansour, N. M. Galal, and A. M. Elmarsafy, "Purine nucleoside phosphorylase (PNP) deficiency: across-the-board severe combined immunodeficiency", Egyptian Journal of Medical Human Genetics, vol. 25, issue 106, 2024.
Hawary, R. E., S. Meshaal, S. Lotfy, D. A. Elaziz, A. S. Eldash, A. Erfan, R. Alkady, R. Darwish, M. Saad, E. Chohayeb, et al., "A novel MALT1 variant in an Egyptian patient presenting with exfoliative dermatitis: a case-based review.", Immunologic research, 2024. Abstract

Inborn errors of the CARD11-BCL10-MALT1 (CBM) signalosome have recently been shown to underlie severe combined immunodeficiency (SCID) and combined immunodeficiency (CID) with variable immunological and clinical phenotypes, and patients usually present with recurrent bacterial, viral, and fungal infections, periodontal disease, enteropathy, dermatitis, and failure to thrive. In the present study, we describe the clinical and immunological characteristics of an Egyptian patient with a mutation in the MALT1 gene. The patient suffered from an itchy exfoliative skin rash and eczematous lesions over his face and flexural surface of the limbs. He also had dental enamel erosion, repeated attacks of diarrhea, and pneumonia. He had elevated serum IgE and normal B- and T-lymphocyte subset counts, but there was an arrest in the B-cell maturation. DOCK8 expression on the lymphocytes by flow cytometry was normal. Next-generation sequencing revealed a novel homozygous variant in the MALT1 gene (c.762dup in exon 5 of 17; p.Ile255TyrfsTer10); this variant is likely pathogenic, thus supporting the genetic diagnosis of immunodeficiency-12 (IMD12). Although the presence of eczema, recurrent sinopulmonary, and staphylococcal infections are suggestive of DOCK8 deficiency, they are also a finding in CARD11 and MALT1 deficiency. Thus, whenever DOCK 8 has been excluded, the molecular diagnosis is mandatory as this could lead to discovering more patients hence better understanding and reporting of the phenotype and natural history of the disease especially since there are very few documented cases. Early diagnosis will also enable the proper patient management by hematopoietic stem cell transplantation (HSCT) prior to the establishment of infections and pulmonary damage leading to a better outcome.

Mohamed, S. A., N. R. Kamel, A. E. Fouda, R. E. El Hawary, and M. A. Abdelmegeid, "Association of low vitamin D level and full-term early-onset neonatal sepsis; a case-control study.", Italian journal of pediatrics, vol. 50, issue 1, pp. 101, 2024. Abstract

BACKGROUND: Sepsis is one of the main causes of death in newborns worldwide. Vitamin D levels during fetal and neonatal periods have a significant role in the development of the immunological system. The study aims to evaluate the association between vitamin D levels and the risk of early-onset neonatal sepsis in full-term neonates in a developing country.

METHODS: This case-control study was conducted at the Neonatal Intensive Care Units (NICUs) of Kasr Alainy Hospital, Cairo, Egypt. The study was composed of two groups; the sepsis group involved full-term neonates appropriate for gestational age with sepsis-related clinical signs. The control group included newborns with no signs of clinical/laboratory infection within 72 h of life. Blood samples were collected on admission during the first three days of life in both groups for the measurement of 25-hydroxyvitamin D levels, Complete Blood Count (CBC), C reactive protein (CRP), and blood culture.

RESULTS: Forty-five newborns with clinical and laboratory findings of early-onset neonatal sepsis within 72 h of life were enrolled, and the control group included forty-five newborns with no evidence of sepsis. Vitamin D levels in the sepsis group were significantly lower than in the control group. Apgar score at the first minute was significantly lower in the sepsis group. 57.8% of neonates with sepsis had positive blood cultures. There was a statistical difference between deficient, insufficient, and sufficient vitamin D levels regarding the duration of the NICU stay, which was longer in neonates with deficient vitamin D levels. CRP was significantly higher in neonates with deficient vitamin D levels. The area under the receiver operating characteristic curve for serum vitamin D in the prediction of neonatal sepsis was 0.76 at a cutoff < 19.7(ng/ml).

CONCLUSION: In the current study, full-term newborns with EOS had considerably lower vitamin D levels than healthy controls. Through appropriate vitamin supplementation of the mothers during pregnancy, it could be possible to ensure adequate vitamin D levels for newborns. This may contribute to the reduction of the risk of EOS, together with the other well-known preventive measures (i.e. breastfeeding and intrapartum antibiotic prophylaxis).

Saad, M. M., R. Alkady, A. Eldash, R. E. El Hawary, S. S. Meshaal, N. M. Galal, and A. M. Elmarsafy, "Analysis of Clinical, Immunological and Molecular Features of Leukocyte Adhesion Deficiency Type I in Egyptian Children.", Journal of clinical immunology, vol. 44, issue 4, pp. 92, 2024. Abstract

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.

Meshaal, S., R. EI Hawary, D. S. Abd Elaziz, A. Eldash, R. Darwish, A. Erfan, S. Lotfy, M. Saad, E. Chohayeb, R. Alkady, et al., "Novel homozygous CARD11 variants in two patients with combined immunodeficiency and atopic skin disease", Egyptian Journal of Medical Human Genetics , vol. 25, 2024.
Hawary, R. E., S. Meshaal, S. Lotfy, D. A. Elaziz, R. Alkady, A. Eldash, A. Erfan, E. Chohayeb, M. Saad, R. Darwish, et al., "Cernunnos deficiency: Further delineation in 5 Egyptian patients.", European journal of medical genetics, vol. 66, issue 10, pp. 104840, 2023. Abstract

Cernunnos deficiency is a rare genetic disorder characterized by immunodeficiency, microcephaly, growth retardation, bird-like facies, sensitivity to ionizing radiation, few autoimmune manifestations, premature aging of hematopoietic stem cells at an early age, and occasional myeloproliferative disease. Herein we present five Egyptian Cernunnos patients from 3 different families. We describe the patients' clinical phenotypes, their immunological profile as well as genetic results. Sequence analysis revealed three different mutations in the NHEJ1 gene: a nonsense variant c.532C > T; p.(Arg178Ter), an intronic variant c.178-1G > A and a frameshift insertion variant c.233dup; p.(Asn78LysfsTer14). In conclusion, Cernunnos deficiency can have a wide range of clinical features. The characteristic immune profile including a decrease in recent thymic emigrants and naive T cells, markedly elevated memory T cells together with normal to high IgM, and a decrease in IgG and IgA. This immune profile is highly suggestive of Cernunnos deficiency in T-B-NK + SCID patients especially surviving for older ages.

Elaziz, D. A., R. E. Hawary, S. Meshaal, R. Alkady, S. Lotfy, A. Eldash, A. Erfan, E. Chohayeb, M. Saad, J. Boutros, et al., "Chronic Granulomatous Disease: a Cohort of 173 Patients-10-Years Single Center Experience from Egypt.", Journal of clinical immunology, 2023. Abstract

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 p47 defect, 44 patients (25.4%) with p22 defect, and 5 patients (2.9%) with p67 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.

Omar, M. A., R. E. Hawary, A. Eldash, K. M. Sadek, N. A. Soliman, M. O. F. Hanna, and S. M. Shawky, "Neutrophilic Myeloid-Derived Suppressor Cells and Severity in SARS-CoV-2 Infection.", Laboratory medicine, 2023. Abstract

BACKGROUND: While we strive to live with SARS-CoV-2, defining the immune response that leads to recovery rather than severe disease remains highly important. COVID-19 has been associated with inflammation and a profoundly suppressed immune response.

OBJECTIVE: To study myeloid-derived suppressor cells (MDSCs), which are potent immunosuppressive cells, in SARS-CoV-2 infection.

RESULTS: Patients with severe and critical COVID-19 showed higher frequencies of neutrophilic (PMN)-MDSCs than patients with moderate illness and control individuals (P = .005). Severe disease in individuals older and younger than 60 years was associated with distinct PMN-MDSC frequencies, being predominantly higher in patients of 60 years of age and younger (P = .004). However, both age groups showed comparable inflammatory markers. In our analysis for the prediction of poor outcome during hospitalization, MDSCs were not associated with increased risk of death. Still, patients older than 60 years of age (odds ratio [OR] = 5.625; P = .02) with preexisting medical conditions (OR = 2.818; P = .003) showed more severe disease and worse outcome. Among the immunological parameters, increased C-reactive protein (OR = 1.015; P = .04) and lymphopenia (OR = 5.958; P = .04) strongly identified patients with poor prognosis.

CONCLUSION: PMN-MDSCs are associated with disease severity in COVID-19; however, MDSC levels do not predict increased risk of death during hospitalization.

R., E., and O. O., "Amniotic membrane derived mesenchymal stem cells: Potential therapeutic application", Egyptian journal of laboratory medicine , vol. 26, issue 1, pp. 53-60, 2014.