Ali Sobh | Mansoura University (original) (raw)

Papers by Ali Sobh

Research paper thumbnail of Vitamin D profile in autism spectrum disorder children and its relation to the disease severity

The Egyptian Journal of Otolaryngology, Jan 17, 2024

Background The study aimed to investigate whether vitamin D deficiency is a common finding in aut... more Background The study aimed to investigate whether vitamin D deficiency is a common finding in autism spectrum disorder (ASD) children and whether such deficiency is related to ASD severity and language age or not. Methods A cross-sectional observational study was conducted on ASD children aged 2-6 years. The participants were 80 Egyptian children with ASD. All participants were assessed using DSM-V, the Childhood Autism Rating Scale (CARS), language assessment, and assessment of serum vitamin D using ADVIA Centaur Vit D assay. Results About 63.8% of ASD children have vitamin D insufficiency, 28.8 % have vitamin D deficiency, and 7.4% have normal serum levels. No correlation was found between serum vitamin D and language age (r =-0.085, P = 0.451), DSM 5 severity levels (r = 0.015 , P= 0.894), and CARS scores (r= 0.075, P= 0.511). Conclusion ASD children have lower serum vitamin D levels, which may be one of the environmental factors contributing to ASD development in genetically susceptible individuals, and its correction may be helpful as adjuvant therapy for ASD.

Research paper thumbnail of Correction: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Genome Medicine, Jan 5, 2024

Reference 1. Matuozzo, et al. Rare predicted loss-of-function variants of type I IFN immunity gen... more Reference 1. Matuozzo, et al. Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19. Genome Med. 2023;15:22.

Research paper thumbnail of Treg cell dysfunction and cutaneous exposure to S. aureus underlie eczema in DOCK8 deficiency

Journal of Allergy and Clinical Immunology, Dec 31, 2023

Research paper thumbnail of A Novel Homozygous Mutation in IL10RA Causing Severe Infantile Onset IBD

Research paper thumbnail of Autoimmune Lymphoproliferative Syndrome in Two Siblings with a Homozygous Fasl Mutation That Affects Protein Oligomerization and Function

Research paper thumbnail of Genotype and functional correlates of disease phenotype in deficiency of adenosine deaminase 2 (DADA2)

The Journal of Allergy and Clinical Immunology, Jun 1, 2020

Research paper thumbnail of Outcome of COVID-19 in patients with rheumatic diseases treated with immunosuppressive drugs

Mansoura Medical Journal

Outcome of COVID-19 in patients with rheumatic diseases treated with Outcome of COVID-19 in patie... more Outcome of COVID-19 in patients with rheumatic diseases treated with Outcome of COVID-19 in patients with rheumatic diseases treated with immunosuppressive drugs immunosuppressive drugs

Research paper thumbnail of Clinical and Immunological Impacts of Latent Toxoplasmosis on COVID-19 Patients

Research paper thumbnail of Genome-scale CRISPR screens identify host factors that promote human coronavirus infection

Genome Medicine, 2022

Background The COVID-19 pandemic has resulted in 275 million infections and 5.4 million deaths as... more Background The COVID-19 pandemic has resulted in 275 million infections and 5.4 million deaths as of December 2021. While effective vaccines are being administered globally, there is still a great need for antiviral therapies as antigenically novel SARS-CoV-2 variants continue to emerge across the globe. Viruses require host factors at every step in their life cycle, representing a rich pool of candidate targets for antiviral drug design. Methods To identify host factors that promote SARS-CoV-2 infection with potential for broad-spectrum activity across the coronavirus family, we performed genome-scale CRISPR knockout screens in two cell lines (Vero E6 and HEK293T ectopically expressing ACE2) with SARS-CoV-2 and the common cold-causing human coronavirus OC43. Gene knockdown, CRISPR knockout, and small molecule testing in Vero, HEK293, and human small airway epithelial cells were used to verify our findings. Results While we identified multiple genes and functional pathways that have...

Research paper thumbnail of Outcome of autoimmune cytopenia after hematopoietic cell transplantation in primary immunodeficiency

The Journal of Allergy and Clinical Immunology, Aug 1, 2020

BACKGROUND Post hematopoietic cell transplantation (HCT) autoimmune cytopenia (AIC) is a potentia... more BACKGROUND Post hematopoietic cell transplantation (HCT) autoimmune cytopenia (AIC) is a potential life-threatening complication but studies focusing on large cohorts of patients transplanted for primary immunodeficiency (PID) are lacking. OBJECTIVE We aimed to study the incidence, risk factors and outcomes of post-HCT AIC and B-lymphocyte function following rituximab. METHODS Retrospective study of 502 PID children who were transplanted at our centre between 1987 and 2018. RESULTS Thirty-six (9%) developed post-HCT AIC, with a median onset of 6.5 months post-HCT. On univariate analysis, pre-HCT AIC, mismatched donor, alemtuzumab, ATG, acute and chronic GvHD were significantly associated with post-HCT AIC. After multivariate analysis, alemtuzumab (SHR 9.0, 95% CI, 1.50-54.0, p=0.02) was independently associated with post-HCT AIC. Corticosteroid and high-dose intravenous immunoglobulin (IVIG) achieved remission in 50% (n=18), additional rituximab led to remission in 25% (n=9), and the remaining 25% were treated with a combination of various modalities including sirolimus (n=5), bortezomib (n=3), mycophenolate mofetil (n=2), splenectomy (n=2), and second HCT (n=3). The mortality of post-HCT AIC reduced from 25% (4/16) prior to 2011 to 5% (1/20) after 2011. The median follow-up of 5.8 years (range, 0.4 to 29.1 years) showed that 26 of 30 survivors (87%) were in complete remission, 4 were in remission with ongoing sirolimus and low dose steroid. Of 17 who received rituximab, 7 had B-lymphocyte recovery, 5 had persistent low B-lymphocyte count and remained on IVIG replacement, 2 had second HCT and 3 died. CONCLUSION The frequency of post HCT AIC in out cohort was 9%, and the most significant risk factors for its occurrence were the presence of GvHD and the use of alemtuzumab.

Research paper thumbnail of Chronic mucocutaneous candidiasis associated with an SH2 domain gain-of-function mutation that enhances STAT1 phosphorylation

The Journal of Allergy and Clinical Immunology, Jul 1, 2016

Research paper thumbnail of Prevalence of acute bronchiolitis during COVID-19 era: an observational study of a tertiary center

Alexandria Journal of Pediatrics, 2023

Research paper thumbnail of Impact of Different Ex Vivo T-Cell Depletion Strategies on Outcomes Following Hematopoietic Cell Transplantation for Children with Primary Immunodeficiency

Biology of Blood and Marrow Transplantation, Mar 1, 2020

Allogeneic hematopoietic stem cell transplantation (HSCT) is curative therapy for a variety of pr... more Allogeneic hematopoietic stem cell transplantation (HSCT) is curative therapy for a variety of primary immunodeficiency disorders (PIDs). Patients with PID have high rates of pulmonary disease from infections and immune-mediated lung damage, and post-HSCT pulmonary complications account for considerable morbidity and mortality. It is unknown whether pre-HSCT pulmonary disease places PID patients at higher risk for post-HSCT complications. We hypothesize that PID patients with pre-HSCT pulmonary disease have higher risk of transplant-related mortality (TRM), more pulmonary complications, and lower overall survival (OS) compared to PID patients without pre-HSCT pulmonary disease. Objectives: The primary aim of this study is to compare TRM in PID patients with and without pre-HSCT pulmonary disease. Secondary aims of the study are to compare OS, incidence of non-infectious and infectious pulmonary disease post-HSCT, ICU transfer for any cause, incidence of acute or chronic GVHD, and immune reconstitution. Methods: This is a single center, retrospective, chart review. All pediatric patients (ages 0-18 years) who underwent allogeneic HSCT for a diagnosis of a PID at Boston Children's Hospital from January 2007-June 2018 (n=115) were included in the analysis. We defined non-infectious pulmonary disease as either functional lung impairment based on pulmonary function tests (PFTs), radiographic evidence of pulmonary disease, or documentation of a specific pulmonary diagnosis. We defined infectious pulmonary disease as either viral, bacterial, fungal or other infection in conjunction with positive radiographic and/or bronch/BAL findings. Results: Within our cohort, the most common PIDs were SCID (n=28), DOCK8 deficiency (n=16), Wiskott-Aldrich syndrome (n=15), and chronic granulomatous disease (n=9). Of the 115 patients, 54 (47%) had a pre-HSCT diagnosis of pulmonary disease. Pulmonary infection (n=30) and bronchiectasis (n=11) were the most common diagnoses (Fig. 1A). Compared to patients without pre-HSCT lung disease, patients with pre-HSCT lung disease had higher numbers of pulmonary complications after HSCT, such as the need for non-invasive or mechanical ventilation (23 of 54 patients [43%] vs. 12 of 61 patients [20%]) (Fig. 1B). Amongst patients with pre-HSCT lung disease, 1-year survival was 81% compared with 92% in patients without pre-HSCT lung disease. Overall survival was 76% at a median follow up time of 1.6 years versus 89% at a median follow up of 2.7 years in patients with and without pre-HSCT lung disease, respectively (censored logrank p = 0.05) (Fig. 2). Conclusion: Within our single center study, PID patients with pre-HSCT lung disease had a trend towards more post-HSCT lung complications and lower OS compared to PID patients without pre-HSCT lung disease. Pulmonary risk factors should be carefully considered in PID patients prior to HSCT.

Research paper thumbnail of Severe combined immunodeficiency caused by inositol-trisphosphate 3-kinase B (ITPKB) deficiency

The Journal of Allergy and Clinical Immunology, Jun 1, 2020

each have an equity stake in Nocion Therapeutics. The rest of the authors declare that they have ... more each have an equity stake in Nocion Therapeutics. The rest of the authors declare that they have no relevant conflicts of interest.

Research paper thumbnail of Clinical and Genetic Characteristics of Children with Inborn Errors of Immunity from Egypt: A single Centre Study

Research Square (Research Square), Jan 6, 2023

Inborn errors of immunity (IEI) comprise a heterogeneous group of monogenic disorders with wide s... more Inborn errors of immunity (IEI) comprise a heterogeneous group of monogenic disorders with wide spectrum of clinical manifestations. The aim of this study is to describe epidemiologic, clinical, and genetic features of patients with inborn errors of immunity in Mansoura University Children's Hospital, a tertiary care center in Egypt. Methods We included patients seen during the period between 2014-2022. Data collected included sociodemographic, clinical features, laboratory investigations, management, and outcome. Results We enrolled 184 patients. The male/female ratio was 1.8:1. The age of onset of symptoms ranged between 2 and 24 months. The age at diagnosis ranged between 12 and 33.5 months with a diagnostic delay range of 0 to 213 months. One hundred and fteen patients (62.5%) were born to consanguineous parents and family history was positive in 59 patients (32.1%). The most common category was immunode ciencies affecting cellular and humoral immunity with Seventy-seven patients (41.8%). A causative mutation was identi ed in 106 patients (57.6% of all cases) with a diagnostic yield of 82.8%. The overall case fatality rate was 48 patients (26.1%). Conclusion Despite a single centre study, this data set may act as a nidus for setting up a national registry of IEIs disorders in Egypt. This study indicates that PIDs are not uncommon in Egypt and that immunode ciencies affecting cellular and humoral immunity is the most common category. Introduction of wide-scale genetic tests allow early diagnosis and treatment that improve the quality of life. genes [13], and the large number of potentially causative mutations in novel genes, genetic testing has assumed increasing importance in the nal diagnosis establishment and management of PIDs [14]. Early molecular diagnosis provides the opportunity for timely treatment such as antibody replacement and hematopoietic stem cell transplantation, which may help prevent disease-related complications and death. Genetic diagnoses also enable the use of targeted therapies such as immune suppression, treatment with monoclonal antibodies or speci c small molecule inhibitors, or gene therapy, which may also signi cantly improve the patients' outcome [15, 16]. Furthermore, genetic diagnosis facilitates genetic counseling, prenatal, and preimplantation genetic diagnosis, and premarital carrier testing. In addition, it provides important information about phenotype-genotype correlation, with important prognostic and therapeutic implications [17, 18]. Societies with high incidence of consanguineous marriages have a high incidence of genetic diseases including primary immunode ciency and immune dysregulation compared to western countries [19, 20, 21]. Region and country speci c accurate estimates of prevalence and genotypes are needed to formulate national plans for the diagnosis and management of these PIDs. Our study aimed to strengthen our understanding of this disease by analysis of demographics, clinical characteristics, categories, genetic features, treatment modalities and outcome of children with IEI in Egypt. Furthermore, this work will be a nucleus for a registry of Primary immunode ciency in Egypt 2. Methods This retrospective study was conducted on children with IEIs who attended to Mansoura University Children's Hospital, which is a tertiary referral hospital and a specialized Pediatric Immunology Service center in Egypt at the period between 2014-2022. 2.1 Classi cation and diagnosis All the children ful lling the European Society of Immunode ciency disorders (ESID) criteria for PID diagnosis were classi ed using the International Union of Immunological Societies (IUIS) phenotypic classi cation for PID [1, 22]. According to the 2022 Updated IUIS classi cation, IEI were classi ed into 10 groups: cellular and humoral immunity immunode ciencies, combined immunode ciency (CID) with associated or syndromic features, predominantly antibody de ciency, diseases of immune dysregulation, congenital defects of phagocytes, defects in intrinsic and innate immunity, autoin ammatory disorders, complement de ciency, bone marrow failure, and phenocopies of IEI [22]. Inclusion criteria: Children who ful lled the clinical and laboratory criteria for a speci c IEI classi cation group Exclusion criteria: Cases with secondary immunode ciency 2.2 Data collection All clinical data were obtained from the medical records of hospitalized patients and outpatients and including, patient demographics, full history, consanguinity, clinical examination, detailed therapeutics, and disease outcome. In addition, laboratory evaluation included all or some of the following guided by the clinical presentation; complete blood count with differential, serum immunoglobulins (IgG, IgA, IgM and IgE), IgG subclasses, lymphocyte immunophenotyping (CD3, CD4, CD8, CD19, and CD16/56), and speci c antibody titers to diphtheria, tetanus, haemophilus in uenza, and pneumococcal serotypes. Dihydrorhodamine 1, 2, 3 (DHR 1, 2, 3) test to assess phagocyte function and functional complement assays CH50 and AH50 were performed. Bone marrow examination, autoimmune pro le (RF, ANA, C3, and Coombs test) as indicated. Genetic analysis

Research paper thumbnail of Thoracic Fluid Content in Neonates Presented with Respiratory Distress as a Predictive Tool for Transient Tachypnea of Newborn

American Journal of Perinatology, Jul 10, 2022

Introduction Respiratory conditions are the most common reason for admission of newborns to a neo... more Introduction Respiratory conditions are the most common reason for admission of newborns to a neonatal care unit. The index of contractility (ICON) can be used to measure the thoracic fluid content (TFC) in neonates which is a significant parameter in cases presented with transient tachypnea of newborn (TTN). Objective The objective was to compare TFC between newborn infants with TTN compared with other causes of respiratory distress (RD). We tested the hypothesis that TFC would be higher in infants with TTN. Study Design In total, 105 newborns were enrolled at the delivery room and were categorized into three groups: TTN, other causes of RD, and control, according to physical examination and Chest X-Ray. TFC was measured within the first 6 hours for all infants and at 24 and 48 hours for the first two groups. Results Demographic data showed higher male participants and use of antenatal steroid therapy in RD groups. TFC within the first 6 hours was higher in RD groups. However, TFC at 24 hours of ≤24 mL/kg, and TFC drop rate at 24 hours of >12% are statistically significant discriminators of TTN from non-TTN, with sensitivity and specificity of 97.1 and 47.1%, and 60 and 82.4%, respectively (Fig 1 and 2). Conclusion ICON can be used in conjunction with clinical parameters and CXR as a tool for differentiation between TTN and other causes of RD within the first 24 hours of life by using the cutoff value of TFC at 24 hours and TFC drop rate. This will allow earlier and optimum management of different causes of RD. Key Points

Research paper thumbnail of Outcome and Risk Factors of Autoimmune Cytopenia after Hematopoietic Cell Transplantation for Children with Primary Immunodeficiency

Biology of Blood and Marrow Transplantation, Mar 1, 2020

Relative to low cell dose therapies, transplant of MGTA-456, a high cell dose therapy with two no... more Relative to low cell dose therapies, transplant of MGTA-456, a high cell dose therapy with two normal IDUA gene copies, led to robust, long-term immune recovery (n=88 animals), 60-fold greater microglial engraftment as early as 2 weeks post-HSCT (Figure D, p<0.001), and >600-fold higher IDUA enzyme levels (Figure E, p<0.001). MGTA-456 enabled use of low-dose busulfan, with 21-fold greater microglial engraftment than that achieved by standard approaches using high-dose busulfan (p<0.01, n=8). Mechanistically, brain microglia are derived from CD34+CD90+ cells, which are present at high numbers in MGTA-456. Conclusions: We show that high dose HSCT leads to improved disease correction, including normalization of behavioral outcomes, via robust engraftment. High dose cell therapies, like MGTA-456, may rapidly and durably resolve peripheral and neurologic disease in patients with IMDs and other neurodegenerative diseases caused by defective microglia.

Research paper thumbnail of Early predictors of colchicine resistance in familial Mediterranean fever

Modern Rheumatology, Jul 5, 2022

ABSTRACT Objective To explore early features that can predict colchicine resistance in familial M... more ABSTRACT Objective To explore early features that can predict colchicine resistance in familial Mediterranean fever (FMF) patients. Methods It included FMF cases who fulfilled the Yalcinkaya–Ozen criterion and were on colchicine for at least 6 months. Data were collected from medical files and interpreted with respect to clinical parameters, incluing the auto-inflammatory diseases activity index (AIDAI) and FMF severity score. FMF50 score assessed the treatment response. Laboratory findings and genetic analysis of Mediterranean fever (MEFV) mutations were evaluated according to the standard technique. Patients were classified into two groups according to their response to colchicine. Both groups were compared, and significant variables were entered into a logistic regression model to detect independent predictors. The diagnostic accuracy of these predictors was assessed using the receiver operating characteristic curve. Results In all, 120 FMF children were included. After the exclusion of 16 non-compliant patients (13.3%), colchicine responders were 66 (63.4%) (group I) and colchicine-resistant cases (group II) were 38 (36.5%). The fever duration after colchicine, number of attacks before/after colchicine, skin rash/erysipelas-like erythema, myalgia/protracted febrile myalgia, AIDAI before/after treatment, FMF severity score, and the maximum colchicine dose were higher in group II. Furthermore, high C-reactive protein and neutropenia were frequent in group II. However, different MEFV mutations, including M694V were similar between the two groups. Eight variables were detected in the regression analysis model, and independent predictors were utilized to generate a scoring model. Conclusion This study constructed a prediction model for colchicine nonresponse based on clinical and laboratory profiles. This model will be valuable for the treatment decisions of FMF children.

Research paper thumbnail of Physicians' knowledge and practice concerning diagnosis and management of anaphylaxis: The situation in Egypt

African Journal of Emergency Medicine, Dec 1, 2021

Introduction Early recognition of an anaphylaxis event is crucial for instituting lifesaving mana... more Introduction Early recognition of an anaphylaxis event is crucial for instituting lifesaving management. We sought to explore knowledge and practice towards anaphylaxis in a sample of physicians from ten Egyptian governorates. Methods An eighteen question-based questionnaire was developed by expert allergists to evaluate the knowledge and practice towards anaphylaxis, based on the World Allergy Organization guidelines for the assessment and management of anaphylaxis. The questionnaires were distributed, and the answered forms collected via emails, and data were tabulated, and analysed. Results In this cross-sectional study, a total of 242 physicians completed the survey (183 (75.6%) paediatricians, 32 (13.2%) internists, 22 (9.1%) intensivists and five (2.1%) anaesthetists). Only 91 participants (37.6%) identified all the four proposed anaphylaxis clinical scenarios while 70, 45 and 36 identified three, two and one scenario, respectively. Loss of consciousness and abdominal symptoms were not recognised as possible presentations of anaphylaxis by 64.5% and 80.2% of the participants, respectively. Epinephrine was considered the first line treatment by 98 (40.5%), corticosteroids by 77 (31.8%) and antihistamines by 25 (10.3%). 75 (31%) responders identified the right dose of epinephrine while 119 (49.2%) identified the proper route. Concerning practice, 83 physicians (39.2%) used epinephrine for all cases of anaphylaxis, 88 (41.5%) used it for refractory cases only whereas 41 (19.3%) did not use epinephrine at all. Discussion Our survey shows that the knowledge of Egyptian physicians and their practice towards anaphylaxis are still inadequate. The current situation reinforces the need to disseminate and encourage the adoption of the international guidelines for anaphylaxis diagnosis and treatment.

Research paper thumbnail of COVID-19 diversity: A case of multisystem inflammatory syndrome in children masquerading as juvenile systemic lupus erythematosus

International Journal of Immunopathology and Pharmacology, 2022

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may present with some syst... more Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may present with some systemic lupus erythematosus (SLE) manifestations intermingled with Kawasaki disease features. These emerging presentations were dubbed under the umbrella term ‘multisystem inflammatory syndrome in children (MIS-C)’. A one and half-year-old girl, admitted to Mansoura University Children’s Hospital (MUCH) with fever, bad general condition, vomiting, widespread maculopapular, vasculitic rash, hands and feet oedema, oral ulceration, arthralgia and lymphadenopathy. Moreover, bicytopenia, positive antinuclear, anti–double-stranded DNA antibodies and low C3 qualified her as a case of juvenile SLE. Despite the child received the initial therapy of immunosuppressive medication, her general condition deteriorated with fever persistence and rash exacerbation. At that time, the skin of her hands and feet started to peel. Thus, an expanded study for other alternatives was obligatory; SARS-CoV-2 infection testing revealed positive IgG serology, and retesting for lupus autoantibodies turned negative. HRCT chest showed bilateral basal consolidation with ground-glass appearance. Furthermore, Echo exhibited coronary artery dilation with thrombus inside. This evolution raised the concern for COVID-related MIS-C syndrome. This report provides a model of COVID-19 heterogeneity with protean immune-related manifestations. This case has a unique presentation that necessities its description, in order to provide a nidus for future studies in this new entity.

Research paper thumbnail of Vitamin D profile in autism spectrum disorder children and its relation to the disease severity

The Egyptian Journal of Otolaryngology, Jan 17, 2024

Background The study aimed to investigate whether vitamin D deficiency is a common finding in aut... more Background The study aimed to investigate whether vitamin D deficiency is a common finding in autism spectrum disorder (ASD) children and whether such deficiency is related to ASD severity and language age or not. Methods A cross-sectional observational study was conducted on ASD children aged 2-6 years. The participants were 80 Egyptian children with ASD. All participants were assessed using DSM-V, the Childhood Autism Rating Scale (CARS), language assessment, and assessment of serum vitamin D using ADVIA Centaur Vit D assay. Results About 63.8% of ASD children have vitamin D insufficiency, 28.8 % have vitamin D deficiency, and 7.4% have normal serum levels. No correlation was found between serum vitamin D and language age (r =-0.085, P = 0.451), DSM 5 severity levels (r = 0.015 , P= 0.894), and CARS scores (r= 0.075, P= 0.511). Conclusion ASD children have lower serum vitamin D levels, which may be one of the environmental factors contributing to ASD development in genetically susceptible individuals, and its correction may be helpful as adjuvant therapy for ASD.

Research paper thumbnail of Correction: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Genome Medicine, Jan 5, 2024

Reference 1. Matuozzo, et al. Rare predicted loss-of-function variants of type I IFN immunity gen... more Reference 1. Matuozzo, et al. Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19. Genome Med. 2023;15:22.

Research paper thumbnail of Treg cell dysfunction and cutaneous exposure to S. aureus underlie eczema in DOCK8 deficiency

Journal of Allergy and Clinical Immunology, Dec 31, 2023

Research paper thumbnail of A Novel Homozygous Mutation in IL10RA Causing Severe Infantile Onset IBD

Research paper thumbnail of Autoimmune Lymphoproliferative Syndrome in Two Siblings with a Homozygous Fasl Mutation That Affects Protein Oligomerization and Function

Research paper thumbnail of Genotype and functional correlates of disease phenotype in deficiency of adenosine deaminase 2 (DADA2)

The Journal of Allergy and Clinical Immunology, Jun 1, 2020

Research paper thumbnail of Outcome of COVID-19 in patients with rheumatic diseases treated with immunosuppressive drugs

Mansoura Medical Journal

Outcome of COVID-19 in patients with rheumatic diseases treated with Outcome of COVID-19 in patie... more Outcome of COVID-19 in patients with rheumatic diseases treated with Outcome of COVID-19 in patients with rheumatic diseases treated with immunosuppressive drugs immunosuppressive drugs

Research paper thumbnail of Clinical and Immunological Impacts of Latent Toxoplasmosis on COVID-19 Patients

Research paper thumbnail of Genome-scale CRISPR screens identify host factors that promote human coronavirus infection

Genome Medicine, 2022

Background The COVID-19 pandemic has resulted in 275 million infections and 5.4 million deaths as... more Background The COVID-19 pandemic has resulted in 275 million infections and 5.4 million deaths as of December 2021. While effective vaccines are being administered globally, there is still a great need for antiviral therapies as antigenically novel SARS-CoV-2 variants continue to emerge across the globe. Viruses require host factors at every step in their life cycle, representing a rich pool of candidate targets for antiviral drug design. Methods To identify host factors that promote SARS-CoV-2 infection with potential for broad-spectrum activity across the coronavirus family, we performed genome-scale CRISPR knockout screens in two cell lines (Vero E6 and HEK293T ectopically expressing ACE2) with SARS-CoV-2 and the common cold-causing human coronavirus OC43. Gene knockdown, CRISPR knockout, and small molecule testing in Vero, HEK293, and human small airway epithelial cells were used to verify our findings. Results While we identified multiple genes and functional pathways that have...

Research paper thumbnail of Outcome of autoimmune cytopenia after hematopoietic cell transplantation in primary immunodeficiency

The Journal of Allergy and Clinical Immunology, Aug 1, 2020

BACKGROUND Post hematopoietic cell transplantation (HCT) autoimmune cytopenia (AIC) is a potentia... more BACKGROUND Post hematopoietic cell transplantation (HCT) autoimmune cytopenia (AIC) is a potential life-threatening complication but studies focusing on large cohorts of patients transplanted for primary immunodeficiency (PID) are lacking. OBJECTIVE We aimed to study the incidence, risk factors and outcomes of post-HCT AIC and B-lymphocyte function following rituximab. METHODS Retrospective study of 502 PID children who were transplanted at our centre between 1987 and 2018. RESULTS Thirty-six (9%) developed post-HCT AIC, with a median onset of 6.5 months post-HCT. On univariate analysis, pre-HCT AIC, mismatched donor, alemtuzumab, ATG, acute and chronic GvHD were significantly associated with post-HCT AIC. After multivariate analysis, alemtuzumab (SHR 9.0, 95% CI, 1.50-54.0, p=0.02) was independently associated with post-HCT AIC. Corticosteroid and high-dose intravenous immunoglobulin (IVIG) achieved remission in 50% (n=18), additional rituximab led to remission in 25% (n=9), and the remaining 25% were treated with a combination of various modalities including sirolimus (n=5), bortezomib (n=3), mycophenolate mofetil (n=2), splenectomy (n=2), and second HCT (n=3). The mortality of post-HCT AIC reduced from 25% (4/16) prior to 2011 to 5% (1/20) after 2011. The median follow-up of 5.8 years (range, 0.4 to 29.1 years) showed that 26 of 30 survivors (87%) were in complete remission, 4 were in remission with ongoing sirolimus and low dose steroid. Of 17 who received rituximab, 7 had B-lymphocyte recovery, 5 had persistent low B-lymphocyte count and remained on IVIG replacement, 2 had second HCT and 3 died. CONCLUSION The frequency of post HCT AIC in out cohort was 9%, and the most significant risk factors for its occurrence were the presence of GvHD and the use of alemtuzumab.

Research paper thumbnail of Chronic mucocutaneous candidiasis associated with an SH2 domain gain-of-function mutation that enhances STAT1 phosphorylation

The Journal of Allergy and Clinical Immunology, Jul 1, 2016

Research paper thumbnail of Prevalence of acute bronchiolitis during COVID-19 era: an observational study of a tertiary center

Alexandria Journal of Pediatrics, 2023

Research paper thumbnail of Impact of Different Ex Vivo T-Cell Depletion Strategies on Outcomes Following Hematopoietic Cell Transplantation for Children with Primary Immunodeficiency

Biology of Blood and Marrow Transplantation, Mar 1, 2020

Allogeneic hematopoietic stem cell transplantation (HSCT) is curative therapy for a variety of pr... more Allogeneic hematopoietic stem cell transplantation (HSCT) is curative therapy for a variety of primary immunodeficiency disorders (PIDs). Patients with PID have high rates of pulmonary disease from infections and immune-mediated lung damage, and post-HSCT pulmonary complications account for considerable morbidity and mortality. It is unknown whether pre-HSCT pulmonary disease places PID patients at higher risk for post-HSCT complications. We hypothesize that PID patients with pre-HSCT pulmonary disease have higher risk of transplant-related mortality (TRM), more pulmonary complications, and lower overall survival (OS) compared to PID patients without pre-HSCT pulmonary disease. Objectives: The primary aim of this study is to compare TRM in PID patients with and without pre-HSCT pulmonary disease. Secondary aims of the study are to compare OS, incidence of non-infectious and infectious pulmonary disease post-HSCT, ICU transfer for any cause, incidence of acute or chronic GVHD, and immune reconstitution. Methods: This is a single center, retrospective, chart review. All pediatric patients (ages 0-18 years) who underwent allogeneic HSCT for a diagnosis of a PID at Boston Children's Hospital from January 2007-June 2018 (n=115) were included in the analysis. We defined non-infectious pulmonary disease as either functional lung impairment based on pulmonary function tests (PFTs), radiographic evidence of pulmonary disease, or documentation of a specific pulmonary diagnosis. We defined infectious pulmonary disease as either viral, bacterial, fungal or other infection in conjunction with positive radiographic and/or bronch/BAL findings. Results: Within our cohort, the most common PIDs were SCID (n=28), DOCK8 deficiency (n=16), Wiskott-Aldrich syndrome (n=15), and chronic granulomatous disease (n=9). Of the 115 patients, 54 (47%) had a pre-HSCT diagnosis of pulmonary disease. Pulmonary infection (n=30) and bronchiectasis (n=11) were the most common diagnoses (Fig. 1A). Compared to patients without pre-HSCT lung disease, patients with pre-HSCT lung disease had higher numbers of pulmonary complications after HSCT, such as the need for non-invasive or mechanical ventilation (23 of 54 patients [43%] vs. 12 of 61 patients [20%]) (Fig. 1B). Amongst patients with pre-HSCT lung disease, 1-year survival was 81% compared with 92% in patients without pre-HSCT lung disease. Overall survival was 76% at a median follow up time of 1.6 years versus 89% at a median follow up of 2.7 years in patients with and without pre-HSCT lung disease, respectively (censored logrank p = 0.05) (Fig. 2). Conclusion: Within our single center study, PID patients with pre-HSCT lung disease had a trend towards more post-HSCT lung complications and lower OS compared to PID patients without pre-HSCT lung disease. Pulmonary risk factors should be carefully considered in PID patients prior to HSCT.

Research paper thumbnail of Severe combined immunodeficiency caused by inositol-trisphosphate 3-kinase B (ITPKB) deficiency

The Journal of Allergy and Clinical Immunology, Jun 1, 2020

each have an equity stake in Nocion Therapeutics. The rest of the authors declare that they have ... more each have an equity stake in Nocion Therapeutics. The rest of the authors declare that they have no relevant conflicts of interest.

Research paper thumbnail of Clinical and Genetic Characteristics of Children with Inborn Errors of Immunity from Egypt: A single Centre Study

Research Square (Research Square), Jan 6, 2023

Inborn errors of immunity (IEI) comprise a heterogeneous group of monogenic disorders with wide s... more Inborn errors of immunity (IEI) comprise a heterogeneous group of monogenic disorders with wide spectrum of clinical manifestations. The aim of this study is to describe epidemiologic, clinical, and genetic features of patients with inborn errors of immunity in Mansoura University Children's Hospital, a tertiary care center in Egypt. Methods We included patients seen during the period between 2014-2022. Data collected included sociodemographic, clinical features, laboratory investigations, management, and outcome. Results We enrolled 184 patients. The male/female ratio was 1.8:1. The age of onset of symptoms ranged between 2 and 24 months. The age at diagnosis ranged between 12 and 33.5 months with a diagnostic delay range of 0 to 213 months. One hundred and fteen patients (62.5%) were born to consanguineous parents and family history was positive in 59 patients (32.1%). The most common category was immunode ciencies affecting cellular and humoral immunity with Seventy-seven patients (41.8%). A causative mutation was identi ed in 106 patients (57.6% of all cases) with a diagnostic yield of 82.8%. The overall case fatality rate was 48 patients (26.1%). Conclusion Despite a single centre study, this data set may act as a nidus for setting up a national registry of IEIs disorders in Egypt. This study indicates that PIDs are not uncommon in Egypt and that immunode ciencies affecting cellular and humoral immunity is the most common category. Introduction of wide-scale genetic tests allow early diagnosis and treatment that improve the quality of life. genes [13], and the large number of potentially causative mutations in novel genes, genetic testing has assumed increasing importance in the nal diagnosis establishment and management of PIDs [14]. Early molecular diagnosis provides the opportunity for timely treatment such as antibody replacement and hematopoietic stem cell transplantation, which may help prevent disease-related complications and death. Genetic diagnoses also enable the use of targeted therapies such as immune suppression, treatment with monoclonal antibodies or speci c small molecule inhibitors, or gene therapy, which may also signi cantly improve the patients' outcome [15, 16]. Furthermore, genetic diagnosis facilitates genetic counseling, prenatal, and preimplantation genetic diagnosis, and premarital carrier testing. In addition, it provides important information about phenotype-genotype correlation, with important prognostic and therapeutic implications [17, 18]. Societies with high incidence of consanguineous marriages have a high incidence of genetic diseases including primary immunode ciency and immune dysregulation compared to western countries [19, 20, 21]. Region and country speci c accurate estimates of prevalence and genotypes are needed to formulate national plans for the diagnosis and management of these PIDs. Our study aimed to strengthen our understanding of this disease by analysis of demographics, clinical characteristics, categories, genetic features, treatment modalities and outcome of children with IEI in Egypt. Furthermore, this work will be a nucleus for a registry of Primary immunode ciency in Egypt 2. Methods This retrospective study was conducted on children with IEIs who attended to Mansoura University Children's Hospital, which is a tertiary referral hospital and a specialized Pediatric Immunology Service center in Egypt at the period between 2014-2022. 2.1 Classi cation and diagnosis All the children ful lling the European Society of Immunode ciency disorders (ESID) criteria for PID diagnosis were classi ed using the International Union of Immunological Societies (IUIS) phenotypic classi cation for PID [1, 22]. According to the 2022 Updated IUIS classi cation, IEI were classi ed into 10 groups: cellular and humoral immunity immunode ciencies, combined immunode ciency (CID) with associated or syndromic features, predominantly antibody de ciency, diseases of immune dysregulation, congenital defects of phagocytes, defects in intrinsic and innate immunity, autoin ammatory disorders, complement de ciency, bone marrow failure, and phenocopies of IEI [22]. Inclusion criteria: Children who ful lled the clinical and laboratory criteria for a speci c IEI classi cation group Exclusion criteria: Cases with secondary immunode ciency 2.2 Data collection All clinical data were obtained from the medical records of hospitalized patients and outpatients and including, patient demographics, full history, consanguinity, clinical examination, detailed therapeutics, and disease outcome. In addition, laboratory evaluation included all or some of the following guided by the clinical presentation; complete blood count with differential, serum immunoglobulins (IgG, IgA, IgM and IgE), IgG subclasses, lymphocyte immunophenotyping (CD3, CD4, CD8, CD19, and CD16/56), and speci c antibody titers to diphtheria, tetanus, haemophilus in uenza, and pneumococcal serotypes. Dihydrorhodamine 1, 2, 3 (DHR 1, 2, 3) test to assess phagocyte function and functional complement assays CH50 and AH50 were performed. Bone marrow examination, autoimmune pro le (RF, ANA, C3, and Coombs test) as indicated. Genetic analysis

Research paper thumbnail of Thoracic Fluid Content in Neonates Presented with Respiratory Distress as a Predictive Tool for Transient Tachypnea of Newborn

American Journal of Perinatology, Jul 10, 2022

Introduction Respiratory conditions are the most common reason for admission of newborns to a neo... more Introduction Respiratory conditions are the most common reason for admission of newborns to a neonatal care unit. The index of contractility (ICON) can be used to measure the thoracic fluid content (TFC) in neonates which is a significant parameter in cases presented with transient tachypnea of newborn (TTN). Objective The objective was to compare TFC between newborn infants with TTN compared with other causes of respiratory distress (RD). We tested the hypothesis that TFC would be higher in infants with TTN. Study Design In total, 105 newborns were enrolled at the delivery room and were categorized into three groups: TTN, other causes of RD, and control, according to physical examination and Chest X-Ray. TFC was measured within the first 6 hours for all infants and at 24 and 48 hours for the first two groups. Results Demographic data showed higher male participants and use of antenatal steroid therapy in RD groups. TFC within the first 6 hours was higher in RD groups. However, TFC at 24 hours of ≤24 mL/kg, and TFC drop rate at 24 hours of &gt;12% are statistically significant discriminators of TTN from non-TTN, with sensitivity and specificity of 97.1 and 47.1%, and 60 and 82.4%, respectively (Fig 1 and 2). Conclusion ICON can be used in conjunction with clinical parameters and CXR as a tool for differentiation between TTN and other causes of RD within the first 24 hours of life by using the cutoff value of TFC at 24 hours and TFC drop rate. This will allow earlier and optimum management of different causes of RD. Key Points

Research paper thumbnail of Outcome and Risk Factors of Autoimmune Cytopenia after Hematopoietic Cell Transplantation for Children with Primary Immunodeficiency

Biology of Blood and Marrow Transplantation, Mar 1, 2020

Relative to low cell dose therapies, transplant of MGTA-456, a high cell dose therapy with two no... more Relative to low cell dose therapies, transplant of MGTA-456, a high cell dose therapy with two normal IDUA gene copies, led to robust, long-term immune recovery (n=88 animals), 60-fold greater microglial engraftment as early as 2 weeks post-HSCT (Figure D, p<0.001), and >600-fold higher IDUA enzyme levels (Figure E, p<0.001). MGTA-456 enabled use of low-dose busulfan, with 21-fold greater microglial engraftment than that achieved by standard approaches using high-dose busulfan (p<0.01, n=8). Mechanistically, brain microglia are derived from CD34+CD90+ cells, which are present at high numbers in MGTA-456. Conclusions: We show that high dose HSCT leads to improved disease correction, including normalization of behavioral outcomes, via robust engraftment. High dose cell therapies, like MGTA-456, may rapidly and durably resolve peripheral and neurologic disease in patients with IMDs and other neurodegenerative diseases caused by defective microglia.

Research paper thumbnail of Early predictors of colchicine resistance in familial Mediterranean fever

Modern Rheumatology, Jul 5, 2022

ABSTRACT Objective To explore early features that can predict colchicine resistance in familial M... more ABSTRACT Objective To explore early features that can predict colchicine resistance in familial Mediterranean fever (FMF) patients. Methods It included FMF cases who fulfilled the Yalcinkaya–Ozen criterion and were on colchicine for at least 6 months. Data were collected from medical files and interpreted with respect to clinical parameters, incluing the auto-inflammatory diseases activity index (AIDAI) and FMF severity score. FMF50 score assessed the treatment response. Laboratory findings and genetic analysis of Mediterranean fever (MEFV) mutations were evaluated according to the standard technique. Patients were classified into two groups according to their response to colchicine. Both groups were compared, and significant variables were entered into a logistic regression model to detect independent predictors. The diagnostic accuracy of these predictors was assessed using the receiver operating characteristic curve. Results In all, 120 FMF children were included. After the exclusion of 16 non-compliant patients (13.3%), colchicine responders were 66 (63.4%) (group I) and colchicine-resistant cases (group II) were 38 (36.5%). The fever duration after colchicine, number of attacks before/after colchicine, skin rash/erysipelas-like erythema, myalgia/protracted febrile myalgia, AIDAI before/after treatment, FMF severity score, and the maximum colchicine dose were higher in group II. Furthermore, high C-reactive protein and neutropenia were frequent in group II. However, different MEFV mutations, including M694V were similar between the two groups. Eight variables were detected in the regression analysis model, and independent predictors were utilized to generate a scoring model. Conclusion This study constructed a prediction model for colchicine nonresponse based on clinical and laboratory profiles. This model will be valuable for the treatment decisions of FMF children.

Research paper thumbnail of Physicians' knowledge and practice concerning diagnosis and management of anaphylaxis: The situation in Egypt

African Journal of Emergency Medicine, Dec 1, 2021

Introduction Early recognition of an anaphylaxis event is crucial for instituting lifesaving mana... more Introduction Early recognition of an anaphylaxis event is crucial for instituting lifesaving management. We sought to explore knowledge and practice towards anaphylaxis in a sample of physicians from ten Egyptian governorates. Methods An eighteen question-based questionnaire was developed by expert allergists to evaluate the knowledge and practice towards anaphylaxis, based on the World Allergy Organization guidelines for the assessment and management of anaphylaxis. The questionnaires were distributed, and the answered forms collected via emails, and data were tabulated, and analysed. Results In this cross-sectional study, a total of 242 physicians completed the survey (183 (75.6%) paediatricians, 32 (13.2%) internists, 22 (9.1%) intensivists and five (2.1%) anaesthetists). Only 91 participants (37.6%) identified all the four proposed anaphylaxis clinical scenarios while 70, 45 and 36 identified three, two and one scenario, respectively. Loss of consciousness and abdominal symptoms were not recognised as possible presentations of anaphylaxis by 64.5% and 80.2% of the participants, respectively. Epinephrine was considered the first line treatment by 98 (40.5%), corticosteroids by 77 (31.8%) and antihistamines by 25 (10.3%). 75 (31%) responders identified the right dose of epinephrine while 119 (49.2%) identified the proper route. Concerning practice, 83 physicians (39.2%) used epinephrine for all cases of anaphylaxis, 88 (41.5%) used it for refractory cases only whereas 41 (19.3%) did not use epinephrine at all. Discussion Our survey shows that the knowledge of Egyptian physicians and their practice towards anaphylaxis are still inadequate. The current situation reinforces the need to disseminate and encourage the adoption of the international guidelines for anaphylaxis diagnosis and treatment.

Research paper thumbnail of COVID-19 diversity: A case of multisystem inflammatory syndrome in children masquerading as juvenile systemic lupus erythematosus

International Journal of Immunopathology and Pharmacology, 2022

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may present with some syst... more Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may present with some systemic lupus erythematosus (SLE) manifestations intermingled with Kawasaki disease features. These emerging presentations were dubbed under the umbrella term ‘multisystem inflammatory syndrome in children (MIS-C)’. A one and half-year-old girl, admitted to Mansoura University Children’s Hospital (MUCH) with fever, bad general condition, vomiting, widespread maculopapular, vasculitic rash, hands and feet oedema, oral ulceration, arthralgia and lymphadenopathy. Moreover, bicytopenia, positive antinuclear, anti–double-stranded DNA antibodies and low C3 qualified her as a case of juvenile SLE. Despite the child received the initial therapy of immunosuppressive medication, her general condition deteriorated with fever persistence and rash exacerbation. At that time, the skin of her hands and feet started to peel. Thus, an expanded study for other alternatives was obligatory; SARS-CoV-2 infection testing revealed positive IgG serology, and retesting for lupus autoantibodies turned negative. HRCT chest showed bilateral basal consolidation with ground-glass appearance. Furthermore, Echo exhibited coronary artery dilation with thrombus inside. This evolution raised the concern for COVID-related MIS-C syndrome. This report provides a model of COVID-19 heterogeneity with protean immune-related manifestations. This case has a unique presentation that necessities its description, in order to provide a nidus for future studies in this new entity.