- Mansoura, Egypt
- +201013373997
Ali Sobh
Mansoura University, Pediatrics, Faculty Member
- Assistant Professor of Pediatrics and Immunology in Mansoura Faculty of Medicine, Egypt.edit
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... 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 Interests: Genetics, Computational Biology, Biology, Medicine, CRISPR, and 3 moreGene, Clinical Sciences, and Coronavirus
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... 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.
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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... 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
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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... 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.
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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... 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.
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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... 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.
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Background and aims The African Society for Immunodeficiency (ASID), looked to form concise region-friendly guidelines for the clinical diagnosis and management of Inborn Errors of Immunity (IEI). The main objective was to develop these... more
Background and aims The African Society for Immunodeficiency (ASID), looked to form concise region-friendly guidelines for the clinical diagnosis and management of Inborn Errors of Immunity (IEI). The main objective was to develop these guidelines to accommodate for the locally prevalent endemic diseases and the disparity of resources within the continent. Furthermore, the society aimed to publish these guidelines to increase awareness among African physicians, and facilitate patient capture, diagnosis and initial management. Methods The African Society for Immunodeficiency convened an African IEI guidelines taskforce, which developed an initial standard operating procedure. This document entailed the main list of IEI in need of urgent guidelines formulation, validation and review processes. The first group of diseases chosen to start the formulation of the guidelines were diseases of immune dysregulation. Simultaneously, this was associated with assigning a local African IEI guidel...
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Introduction Despite efforts, primary immunodeficiency disorders (PIDs) are still under estimated. Predominantly antibody deficiencies (PADs) account for approximately two-thirds of all PIDs. We sought to screen for immunoglobulin... more
Introduction Despite efforts, primary immunodeficiency disorders (PIDs) are still under estimated. Predominantly antibody deficiencies (PADs) account for approximately two-thirds of all PIDs. We sought to screen for immunoglobulin deficiency among Egyptian infants and children presenting with unusually recurrent, severe and/ or persistent infections. Methods We conducted a cross sectional study that included 75 children presenting with clinical history and/or features suggestive of immunodeficiency. They were enrolled from Children’s Hospitals of Ain Shams and Mansoura Universities. They were subjected to clinical evaluation and measurement of serum immunoglobulin (Ig) levels: IgA, IgG and IgM (by nephelometry) and IgE (by ELISA). Results Patients’ ages ranged between 0.5-14 years (median (IQR): 2(0.83-3) with male to female ratio 2:1. Pneumonia was the most common infection (84%) followed by gastroenteritis (64%). Eleven patients (14.7%) had allergic manifestations and three (4%) h...
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Research Interests: Immunology, Humans, Mutation, Female, Animals, and 5 moreMale, Infant, Clinical Allergy and Immunology, Fas Ligand, and CHO cells
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BackgroundWe previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of... more
BackgroundWe previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants wasTLR7, with an OR of 27.68 (95%CI:1.5-528.7,P=1.1×10−4), in analyses restricted to biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-de...
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Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1 , OAS2 , or RNASEL in five unrelated children with MIS-C. The cytosolic... more
Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1 , OAS2 , or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)–sensing OAS1 and OAS2 generate 2′-5′-linked oligoadenylates (2-5A) that activate the single-stranded RNA–degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L–deficient cells. Cytokine production in RNase L–deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS–RNase L deficiencies in these patients unleash the production of SARS-CoV-2–triggered,...
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Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1 , OAS2 , or RNASEL in five unrelated children with MIS-C. The cytosolic... more
Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1 , OAS2 , or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)–sensing OAS1 and OAS2 generate 2′-5′-linked oligoadenylates (2-5A) that activate the single-stranded RNA–degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L–deficient cells. Cytokine production in RNase L–deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS–RNase L deficiencies in these patients unleash the production of SARS-CoV-2–triggered,...
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Background About 25–50% of multisystem inflammatory syndrome in children (MIS-C) patients meet the criteria for diagnosis of Kawasaki disease (KD). The differentiation of both conditions is so challenging on clinical practice as the... more
Background About 25–50% of multisystem inflammatory syndrome in children (MIS-C) patients meet the criteria for diagnosis of Kawasaki disease (KD). The differentiation of both conditions is so challenging on clinical practice as the management of both is time dependant and precise diagnosis is fundamental. Method Data were collected from children < 18 years old hospitalized with MIS-C or KD. Patient demographics, clinical, and laboratory data were compared, and a discrimination score was created to assist in clinical differentiation. Results 72 patients with MIS-C and 18 with KD were included in the study. Patients with MIS-C had a higher prevalence of abdominal pain (p = 0.02), vomiting (p = 0.03), and cervical lymphadenopathy (p = 0.02) compared with KD cases. MIS-C patients had higher liver enzymes (aspartate aminotransferase (AST) (p = 0.04), alanine aminotransferase (ALT) (p = 0.03), serum creatinine (p = 0.03), and lower platelet count nadir (p = 0.02) than KD. Four variabl...
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We report a female patient presenting with generalized pustular psoriasis and hypogammaglobulinemia due to digenic mutations in IL-36RA and SEC61A1. The patient presented with recurrent fevers, elevated inflammatory markers,... more
We report a female patient presenting with generalized pustular psoriasis and hypogammaglobulinemia due to digenic mutations in IL-36RA and SEC61A1. The patient presented with recurrent fevers, elevated inflammatory markers, hepatosplenomegaly, and recurrent sinopulmonary infections in the context of hypogammaglobulinemia which improved on immunoglobulin replacement. This report demonstrates how digenic inheritance leads to complex phenotypes, and illustrates the importance of following an unbiased approach to identifying variants, especially in patients with atypical clinical presentations.
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Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics... more
Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates ...
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TLR7 and plasmacytoid dendritic cells are essential for type I IFN–dependent immunity to SARS-CoV-2 in the lungs.
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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... 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 ...
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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... more
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 1...
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Significance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on... more
Significance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population.
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Autoantibodies neutralizing type I IFNs increase in prevalence over 60 years of age and underlie about 20% of all fatal COVID-19 cases.
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The genetics underlying severe COVID-19 The immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). Individuals that lack specific IFNs can be more susceptible to infectious... more
The genetics underlying severe COVID-19 The immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). Individuals that lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody system dampens IFN response to prevent damage from pathogen-induced inflammation. Two studies now examine the likelihood that genetics affects the risk of severe coronavirus disease 2019 (COVID-19) through components of this system (see the Perspective by Beck and Aksentijevich). Q. Zhang et al. used a candidate gene approach and identified patients with severe COVID-19 who have mutations in genes involved in the regulation of type I and III IFN immunity. They found enrichment of these genes in patients and conclude that genetics may determine the clinical course of the infection. Bastard et al. identified individuals with high titers of neutralizing autoantibodies against type I IFN-α2 and IFN-ω in about 10% of ...
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Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify four genomic loci with suggestive associations for SARS-CoV-2 susceptibility and nineteen for... more
Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify four genomic loci with suggestive associations for SARS-CoV-2 susceptibility and nineteen for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. GWAS signals in eleven loci colocalize with eQTLs associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene) including lung, brain, heart, muscle, skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify ten GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome affecting gene expression levels in a wide variety of tissue types.
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The genetics underlying severe COVID-19 The immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). Individuals that lack specific IFNs can be more susceptible to infectious... more
The genetics underlying severe COVID-19 The immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). Individuals that lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody system dampens IFN response to prevent damage from pathogen-induced inflammation. Two studies now examine the likelihood that genetics affects the risk of severe coronavirus disease 2019 (COVID-19) through components of this system (see the Perspective by Beck and Aksentijevich). Q. Zhang et al. used a candidate gene approach and identified patients with severe COVID-19 who have mutations in genes involved in the regulation of type I and III IFN immunity. They found enrichment of these genes in patients and conclude that genetics may determine the clinical course of the infection. Bastard et al. identified individuals with high titers of neutralizing autoantibodies against type I IFN-α2 and IFN-ω in about 10% of ...
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Background: Coronavirus disease 2019 (COVID-19) is responsible for significant lung disease in adults. Despite mild manifestations in most children, multisystem inflammatory syndrome (MIS-C) associated with COVID-19 is well described in... more
Background: Coronavirus disease 2019 (COVID-19) is responsible for significant lung disease in adults. Despite mild manifestations in most children, multisystem inflammatory syndrome (MIS-C) associated with COVID-19 is well described in older children with cardiac manifestations. However, MIS-C-related cardiac manifestations are not as well described in younger children. Methods: The study is a retrospective analysis of MIS-C patients under the age of 5 years admitted between May and November 2020 to a single centre. Included cases fulfilled the case definition of MIS-C according to Royal College of Pediatrics and Child Health criteria with laboratory, electrocardiogram, or echocardiographic evidence of cardiac disease. Collected data included patients’ demographics, laboratory results, echocardiographic findings, management, and outcomes. Results: Out of 16 MIS-C cases under 5 years of age, 10 (62.5%) had cardiac manifestations with a median age of 12 months, 9 (90%) were previousl...
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Hematopoietic cell transplantation (HCT) is a successful curative treatment for an increasing number of primary immunodeficiencies (PID). Despite an increased availability of potential matched donors worldwide including the use of banked... more
Hematopoietic cell transplantation (HCT) is a successful curative treatment for an increasing number of primary immunodeficiencies (PID). Despite an increased availability of potential matched donors worldwide including the use of banked cord bloods, there are a large number of patients for whom no matched donor can be found. Various techniques for T-cell depleting (TCD) mismatched donors have been used over the years to minimize the risks of graft rejection and graft versus host disease (GvHD). This retrospective study compared the outcomes according to TCD methods in 115 children with PID from January 1987 to December 2019. Thirteen patients who received additional genemodified add-back T-cells were excluded. Fourteen patients who received TCR αβ/CD19 depleted mismatched grafts were previously reported by Shah et al. [1]. Outcomes of interest were: overall survival (OS), event-free survival (EFS), GvHD, CD3+ lymphocyte count at 3 months post-HCT, and latest donor chimerism. OS was defined as survival from first HCT to last follow-up or death. An event was defined as death, graft failure or second procedure for slipping chimerism. Subgroup differences in OS and EFS were evaluated by log-rank test. The difference in CD3+ lymphocyte count and donor chimerism between TCD methods was assessed by the Kruskal Wallis test. A detailed description of transplant characteristics and outcomes is summarized in Table 1. The indication for an ex-vivo T-cell depleted graft has changed from predominantly severe combined immunodeficiency (SCID) to non-SCID PID between 1987 and 2019. The majority of exvivo T-cell depletions were performed in haploidentical parental donors (n= 98/115, 85%). Parents (45/47, 96%) were the main donors for CD3/CD19 depletion and TCR αβ/CD19 depletion. Two patients received a TCR αβ/ CD19 depleted mismatched unrelated donor (MMUD) due to unsuitability of their parents. Marrow was used for CAMPATH-1M depletion (n= 34) and CD34 selection (n= 34) while peripheral blood stem cells (PBSC) were used for CD3/CD19 (n= 7) and TCR αβ/CD19 (n= 40) depletions. Prior to 2009, various conditioning regimens were used with the majority (n= 59/63, 94%) undergoing conditioning with busulfan and cyclophosphamide. Serotherapy and GvHD prophylaxis were given according to the institutional guidelines at the time of HCT. From 2009, a myeloablative reduced toxicity conditioning (RTC) regimen of fludarabine, treosulfan, ATG (Grafalon), and rituximab was used for SCID. Thiotepa was added for non-SCID PID. No GvHD prophylaxis was given since 2015 in patients who received grafts with a TCR αβ content of < 5 × 10/kg or unconditioned transplants for SCID (n= 4/12, 33%) due to severe co-morbidities. Fourteen (12%) patients had acute GvHD, of whom 3 (2%) had grade III–IV. None had chronic GvHD. With routine * Su Han Lum s.lum@nhs.net
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Background Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI... more
Background Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis. Methods We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers. Results We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity wa...
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Multisystem inflammatory syndrome in children (MIS-C) emerged in April 2020 in communities with high COVID-19 rates. This new condition is heterogenous but resembles Kawasaki disease (KD), a well-known but poorly understood and clinically... more
Multisystem inflammatory syndrome in children (MIS-C) emerged in April 2020 in communities with high COVID-19 rates. This new condition is heterogenous but resembles Kawasaki disease (KD), a well-known but poorly understood and clinically heterogenous pediatric inflammatory condition for which weak associations have been found with a myriad of viral illnesses. Epidemiological data clearly indicate that SARS-CoV-2 is the trigger for MIS-C, which typically occurs about 1 mo after infection. These findings support the hypothesis of viral triggers for the various forms of classic KD. We further suggest that rare inborn errors of immunity (IEIs) altering the immune response to SARS-CoV-2 may underlie the pathogenesis of MIS-C in some children. The discovery of monogenic IEIs underlying MIS-C would shed light on its pathogenesis, paving the way for a new genetic approach to classic KD, revisited as a heterogeneous collection of IEIs to viruses.