95 results on '"Bousfiha AA"'
Search Results
2. Research of anti-GAD and anti-IA2 autoantibodies by ELISA test in a series of Moroccan pediatric patients with diabetes type 1
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Belhiba, O, primary, Aadam, Z, additional, Jeddane, L, additional, Saile, R, additional, Salih ALJ, H, additional, Bousfiha, AA, additional, and Jennane, F, additional
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- 2020
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3. X-linked agammaglobulinemia (XLA): Phenotype, diagnosis, and therapeutic challenges around the world
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El-Sayed, ZA, Abramova, I, Carlos Aldave, J, Al-Herz, W, Bezrodnik, L, Boukari, R, Bousfiha, AA, Cancrini, C, Condino-Neto, A, Dbaibo, G, Derfalvi, B, Dogu, F, Edgar, JDM, Eley, B, El-Owaidy, RH, Elva Espinosa-Padilla, S, Galal, N, Haerynck, F, Hanna-Wakim, R, Hossny, E, Ikinciogullari, A, Kamal, E, Kanegane, H, Kechout, N, Lau, YL, Morio, T, Moschese, V, Neves, JF, Ouederni, M, Paganelli, R, Paris, K, Pignata, C, Plebani, A, Qamar, FN, Qureshi, S, Radhakrishnan, N, Rezaei, N, Rosario, N, Routes, J, Sanchez, B, Sediva, A, Seppanen, MRJ, Serrano, EG, Shcherbina, A, Singh, S, Siniah, S, Spadaro, G, Tang, M, Maria Vinet, A, Volokha, A, Sullivan, KE, El-Sayed, ZA, Abramova, I, Carlos Aldave, J, Al-Herz, W, Bezrodnik, L, Boukari, R, Bousfiha, AA, Cancrini, C, Condino-Neto, A, Dbaibo, G, Derfalvi, B, Dogu, F, Edgar, JDM, Eley, B, El-Owaidy, RH, Elva Espinosa-Padilla, S, Galal, N, Haerynck, F, Hanna-Wakim, R, Hossny, E, Ikinciogullari, A, Kamal, E, Kanegane, H, Kechout, N, Lau, YL, Morio, T, Moschese, V, Neves, JF, Ouederni, M, Paganelli, R, Paris, K, Pignata, C, Plebani, A, Qamar, FN, Qureshi, S, Radhakrishnan, N, Rezaei, N, Rosario, N, Routes, J, Sanchez, B, Sediva, A, Seppanen, MRJ, Serrano, EG, Shcherbina, A, Singh, S, Siniah, S, Spadaro, G, Tang, M, Maria Vinet, A, Volokha, A, and Sullivan, KE
- Abstract
BACKGROUND: X-linked agammaglobulinemia is an inherited immunodeficiency recognized since 1952. In spite of seven decades of experience, there is still a limited understanding of regional differences in presentation and complications. This study was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to better understand regional needs, challenges and unique patient features. METHODS: A survey instrument was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to collect both structured and semi-structured data on X-linked agammaglobulinemia. The survey was sent to 54 centers around the world chosen on the basis of World Allergy Organization participation and/or registration in the European Society for Immunodeficiencies. There were 40 centers that responded, comprising 32 countries. RESULTS: This study reports on 783 patients from 40 centers around the world. Problems with diagnosis are highlighted by the reported delays in diagnosis>24 months in 34% of patients and the lack of genetic studies in 39% of centers Two infections exhibited regional variation. Vaccine-associated paralytic poliomyelitis was seen only in countries with live polio vaccination and two centers reported mycobacteria. High rates of morbidity were reported. Acute and chronic lung diseases accounted for 41% of the deaths. Unusual complications such as inflammatory bowel disease and large granular lymphocyte disease, among others were specifically enumerated, and while individually uncommon, they were collectively seen in 20.3% of patients. These data suggest that a broad range of both inflammatory, infectious, and autoimmune conditions can occur in patients. The breadth of complications and lack of data on management subsequently appeared as a significant challenge reported by centers. Survival above 20 years of age was lowest in Africa (22%) and reached above 70% in Australia, Europe and the Americas. Centers were asked to rep
- Published
- 2019
4. Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies
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Sullivan, KE, Bassiri, H, Bousfiha, AA, Costa-Carvalho, BT, Freeman, AF, Hagin, D, Lau, YL, Lionakis, MS, Moreira, I, Pinto, JA, de Moraes-Pinto, MI, Rawat, A, Reda, SM, Lugo Reyes, SO, Seppanen, M, Tang, MLK, Sullivan, KE, Bassiri, H, Bousfiha, AA, Costa-Carvalho, BT, Freeman, AF, Hagin, D, Lau, YL, Lionakis, MS, Moreira, I, Pinto, JA, de Moraes-Pinto, MI, Rawat, A, Reda, SM, Lugo Reyes, SO, Seppanen, M, and Tang, MLK
- Abstract
In today's global economy and affordable vacation travel, it is increasingly important that visitors to another country and their physician be familiar with emerging infections, infections unique to a specific geographic region, and risks related to the process of travel. This is never more important than for patients with primary immunodeficiency disorders (PIDD). A recent review addressing common causes of fever in travelers provides important information for the general population Thwaites and Day (N Engl J Med 376:548-560, 2017). This review covers critical infectious and management concerns specifically related to travel for patients with PIDD. This review will discuss the context of the changing landscape of infections, highlight specific infections of concern, and profile distinct infection phenotypes in patients who are immune compromised. The organization of this review will address the environment driving emerging infections and several concerns unique to patients with PIDD. The first section addresses general considerations, the second section profiles specific infections organized according to mechanism of transmission, and the third section focuses on unique phenotypes and unique susceptibilities in patients with PIDDs. This review does not address most parasitic diseases. Reference tables provide easily accessible information on a broader range of infections than is described in the text.
- Published
- 2017
5. UTILISATION DES IMMUNOGLOBULINES HUMAINES CHEZ L'ENFANT
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BOUSFIHA, AA., DEBRE, M., and ABID, A.
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Immunoglobulines intraveineuses, enfant, substitution, immunomodulation - Abstract
Les immunoglobulines intraveineuses (IgIV) sont extraites du plasma humain, puis traitées par solvantsdétergents pour assurer leur inactivation virale. Elles sont utilisées dans deux grandes indications : en traitement substitutif chez les patients hypo- ou agammaglobulinémiques et comme traitement immunomodulateur dans plusieurs affections auto-immunes. En thérapeutique substitutive les déficits immunitaires (DI) primitifs constituent l'indication principale et logique des IgIV. Il s'agit essentiellement des agammaglobulinémies liées ou non au chromosome X, les hypogammaglobulinémies à expression variable, les déficits en sous-classes d'IgG, les syndromes hyper-IgM, ainsi que les DI des cellules T associés à un déficit en anticorps. Dans les DI secondaires, l'infection par le VIH chez l'enfant constitue une indication aux IgIV s'il existe une hypogammaglobulinémie (IgG, Maroc Médical, Vol. 22, No 3 (2000)
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- 2013
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6. The 752delG26 mutation in the RFXANK gene associated with major histocompatibility complex class II deficiency: evidence for a founder effect in the Moroccan population
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Naamane, H, primary, Ailal, F, additional, Abidi, O, additional, Jeddane, L, additional, Najib, J, additional, Barakat, A, additional, and Bousfiha, AA, additional
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- 2011
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7. Complement system activation: bridging physiology, pathophysiology, and therapy.
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Azoulay E, Zuber J, Bousfiha AA, Long Y, Tan Y, Luo S, Essafti M, and Annane D
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- Humans, Myasthenia Gravis physiopathology, Myasthenia Gravis immunology, Myasthenia Gravis therapy, SARS-CoV-2 immunology, Complement System Proteins immunology, Antibodies, Monoclonal, Humanized, Complement Activation drug effects, Complement Activation immunology, COVID-19 immunology, COVID-19 physiopathology, COVID-19 complications, COVID-19 therapy, Atypical Hemolytic Uremic Syndrome physiopathology, Atypical Hemolytic Uremic Syndrome immunology, Atypical Hemolytic Uremic Syndrome therapy, Complement Inactivating Agents therapeutic use
- Abstract
The complement system is a set of over 50 proteins that constitutes an essential part of the innate immune system. Complement system activation involves an organized proteolytic cascade. Overactivation of complement system activation is the main pathogenic mechanism of several diseases and contributes to the manifestations of many other conditions. This review describes the normal complement system and the role for complement dysregulation in critical illnesses, notably sepsis and acute respiratory distress syndrome. Complement activation is involved in the immune system response to pathogens but, when excessive, can contribute to tissue damage, runaway inflammation, and capillary leakage syndrome. Complement overactivation may play a key role in severe forms of coronavirus disease 2019 (COVID-19). Two diseases whose manifestations are mainly caused by complement overactivation, namely, atypical hemolytic and uremic syndrome (aHUS) and myasthenia gravis, are discussed. A diagnostic algorithm for aHUS is provided. Early complement-inhibiting therapy has been proven effective. When renal transplantation is required, complement-inhibiting drugs can be used prophylactically to prevent aHUS recurrence. Similarly, acetylcholine-receptor autoantibody-positive generalized myasthenia gravis involves complement system overactivation and responds to complement inhibition. The two main complement inhibitors used in to date routine are eculizumab and ravulizumab. The main adverse event is Neisseria infection, which is rare and preventable, but can be fatal. The complement system is crucial to health but, when overactivated, can cause or contribute to disease. Effective complement inhibitors are now available, although additional data are required to determine optimal regimens. Further research is also needed to better understand the complement system, develop advanced diagnostic tools, and identify markers that allow the personalization of treatment strategies., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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8. Multisystem Inflammatory Syndrome in Children (MIS-C) Associated With COVID-19 Infection in Morocco.
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Amenzoui N, Zouiter S, Nassid M, Kholaiq H, Belkhou I, Benhsaien I, Ailal F, Adnane F, Jouhadi Z, and Bousfiha AA
- Abstract
Introduction . This study aims to describe the clinical and paraclinical characteristics of Multisysteminflammatory syndrome in children (MIS-C). Methods . A retrospective study encompassing 52 children diagnosed with MIS-C according to the World Health Organization criteria, over a 3-year period at Abderrahim Harrouchi Hospital in Morocco. Results . The median age was 6 years (IQR: 1-14), with a sex ratio of 1.16 (28 boys and 24 girls). Clinical manifestations were predominantly characterized by fever in all cases (100%), respiratory and gastrointestinal symptoms in 30 cases (58%) and 23 cases (44%) respectively, and shock in 9 cases (17%). We noted a myocarditis in 6 cases (12%). The treatment comprised intravenous human Immunoglobulin combined with methylprednisolone in all patients (100%). Conclusion . The characteristics of our MIS-C patients were similar to those in the literature, but more studies are needed to confirm these results., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)
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- 2024
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9. Phenotypes of 126 Moroccan HIES patients according to NIH Score.
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Fadil I, Benhsaien I, El Bakkouri J, Jeddane L, Benaajiba N, Rada N, Hbibi M, Amenzoui N, Ben Miloud S, Hida M, Bouskraoui M, El Fetoiki FZ, Hali F, Chiheb S, Admou B, Casanova JL, Puel A, Boisson B, Beziat V, Ailal F, and Bousfiha AA
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- Humans, Morocco epidemiology, Retrospective Studies, Female, Child, Preschool, Male, Child, Infant, Adolescent, Young Adult, Adult, Dermatitis, Atopic epidemiology, Dermatitis, Atopic diagnosis, Phenotype
- Abstract
Introduction: Hyper-IgE syndrome is a group of inborn errors of immunity, some of which are syndromic, characterized clinically by the classic triad of chronic eczema, cutaneous and/or pulmonary staphylococcal infections and high serum IgE concentrations (> 2000 IU/ml or > 10 x normal for age)., Aim: We report here the clinical and immunological aspects of Moroccan patients presenting probable or possible HIES according to NIH-HIES score., Methods: This retrospective study covers the period from 1998 to 2023 and includes Moroccan patients with a clinical presentation suggestive of HIES (skin and/or pulmonary infections, eczema, high IgE levels) and an NIH score ≥ 20. We attempted to classify the patients phenotypically according to the 2022 IUIS IEI Expert Committee classification., Results: Median age at symptom onset was 0.5 years and median age at diagnosis was 5.5 years. The main clinical signs were eczema (66%), skin abscesses (32.5%), pneumonia (32.5%), otitis (20%), mucocutaneous candidiasis (19%), diarrhea (12%), facial dysmorphism (10.3%), lymphadenopathy (9.5%), bronchial dilation (8%), pneumatoceles (8%), conjunctivitis (7.1%), rhinitis (6.3%), psychomotor delay (5.6%), pathological fractures (4%), retention of deciduous teeth (4%), cognitive delay (3.2%)., Conclusion: This is the first clinical description of a cohort of Moroccan patients presenting HIES according to NIH criteria. Phenotype can sometimes orient towards identification of the mutated gene, but the overlapping clinical signs make molecular analysis necessary for genetic counseling and appropriate treatment.
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- 2024
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10. Case Report of Two Independent Moroccan Families with Syndromic Epidermodysplasia Verruciformis and STK4 Deficiency.
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El Kettani A, Ouair H, Marnissi F, El Bakkouri J, Chevalier R, Lorenzo L, Kholaiq H, Béziat V, Jouanguy E, Casanova JL, and Bousfiha AA
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- Humans, Male, Female, Pedigree, Morocco, Exome Sequencing, Child, Child, Preschool, Mutation, Epidermodysplasia Verruciformis genetics, Epidermodysplasia Verruciformis virology, Epidermodysplasia Verruciformis pathology, Protein Serine-Threonine Kinases genetics, Protein Serine-Threonine Kinases deficiency, Intracellular Signaling Peptides and Proteins genetics, Intracellular Signaling Peptides and Proteins deficiency
- Abstract
Epidermodysplasia verruciformis (EV) is a rare genodermatosis caused by β-human papillomaviruses (HPV) in immunodeficient patients. EV is characterized by flat warts and pityriasis-like lesions and might be isolated or syndromic, associated with some other infectious manifestations. We report here three patients from two independent families, with syndromic EV for both of them. By whole exome sequencing, we found that the patients carry new homozygous variants in STK4, both leading to a premature stop codon. STK4 deficiency causes a combined immunodeficiency characterized by a broad infectious susceptibility to bacteria, viruses, and fungi. Auto-immune manifestations were also reported. Deep immunophenotyping revealed multiple cytopenia in the three affected patients, in particular deep CD4
+ T cells deficiency. We report here the fourth and the fifth cases of the syndromic EV due to STK4 deficiency.- Published
- 2024
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11. Insights into the genetic theory of infectious diseases.
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Moundir A, Jeddane L, and Bousfiha AA
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- Humans, COVID-19 genetics, Communicable Diseases genetics, Genetic Predisposition to Disease
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Over the past century, classical approaches from microbiology and immunology have produced spectacular results in the control of infectious diseases. However, the recent SARS-COV-2 pandemic has highlighted our continued failure to control some infections. Other microorganisms still pose a threat to humanity such as HIV, Ebola, and influenza viruses. It seems that conventional approaches are not able to solve all the current problems caused by infectious diseases. Human genetics has shown that infections have a strong genetic determinism that can lead to a predisposition or resistance to infections. This explains much of the clinical variability observed in individuals infected with the same pathogen. The identification of the genetic etiology allows a better understanding of the pathogenesis of infectious diseases and, consequently, the consideration of appropriate preventive and therapeutic strategies. This review provides insights into the genetic theory and the concrete evidence to support it. We highlight the role of primary immunodeficiencies in the discovery of Mendelian and monogenic susceptibility to infections, then we show how genetic and phenotypic heterogeneity, redundancy, and resistance to infection manifest in the context of this genetic determinism. To effectively combat the constant threat of microbes, it is essential to integrate human genetics with microbiology to examine the interactions between pathogens and our immune system.
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- 2024
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12. Invasive Pneumococcal Infections Among Moroccan Children: Pneumococcal Vaccination Challenges in the Mature Vaccine Era.
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Zerouali K, Katfy M, Kettani AE, Nzoyikorera N, Katfy K, Bousfiha AA, Gueddari W, Slaoui B, Abkari A, Chlilek A, Diawara I, Zouhair S, Asmae LH, Younous S, Mouaffak Y, Bourrous M, Lahmini W, Rada N, Draiss G, Soraa N, and Bouskraoui M
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- Humans, Morocco epidemiology, Child, Preschool, Infant, Child, Male, Female, Vaccination statistics & numerical data, Adolescent, Anti-Bacterial Agents therapeutic use, Prevalence, Pneumococcal Vaccines administration & dosage, Pneumococcal Vaccines immunology, Pneumococcal Infections prevention & control, Pneumococcal Infections epidemiology, Pneumococcal Infections microbiology, Streptococcus pneumoniae immunology, Streptococcus pneumoniae classification, Streptococcus pneumoniae isolation & purification, Serogroup
- Abstract
Background: Streptococcus pneumoniae, a major contributor to global morbidity and mortality, disproportionately affects children, the elderly, and immunocompromised individuals. Despite vaccination efforts, the challenge of serotype replacement highlights the ongoing struggle against invasive pneumococcal diseases (IPD) in Morocco, emphasizing the need for updated public health strategies and vaccine efficacy assessments., Methods: This study was conducted at the Ibn Rochd University Hospital Center and the Mohammed VI University Hospital Center from 2019 to 2022, focusing on hospitalized children. It involved the analysis of 74 strains of IPD, assessing the distribution of pneumococcal serotypes and their antibiotic sensitivity in the post-vaccination era., Results: The prevalence of meningitis or meningo-encephalitis was found to be 66% among the study subjects, with the most frequent serotypes being 3, 19A, 6B, 14, and 11. These serotypes varied significantly by age and location. Coverage rates for the pneumococcal conjugate vaccines, PCV-10 and PCV-13, were 20.27% and 56.75%, respectively. Notably, 43% of the strains were non-vaccine serotypes, with serotypes 3 and 19 accounting for 36% of the infections in children, indicating a lack of vaccine efficacy against these types. Additionally, 31.3% of the strains were Penicillin non-susceptible Streptococcus pneumoniae (PNSP), with 81.25% associated with non-vaccine serotypes., Conclusions: This study highlights the persistence of IPD in Moroccan children, revealing significant challenges despite vaccination efforts. With the reintroduction of PCV-13, concerns about the efficacy against non-vaccine serotypes, particularly 3 and 19A, remain. Continuous surveillance and adaptable vaccination strategies are essential to combat these serotype replacements and ensure the effectiveness of future preventive measures.
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- 2024
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13. Tuberculous Meningitis Genetic predisposition: Understanding cellular interactions, molecular mechanisms and genetic dimensions.
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Majambere JC, Zaidi S, Errami A, Marih L, Marhoum El Filali K, Bousfiha AA, and Lahsen AO
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- Humans, Immunity, Innate genetics, Adaptive Immunity genetics, Tuberculosis, Meningeal genetics, Tuberculosis, Meningeal immunology, Genetic Predisposition to Disease, Mycobacterium tuberculosis immunology
- Abstract
Tuberculous meningitis, a severe form of tuberculosis caused by Mycobacterium tuberculosis (BK), remains a major public health challenge worldwide. In addition to the complex mechanisms of the innate and adaptive immune response against Mycobacterium tuberculosis, there is a crucial genetic dimension to consider. Individuals with specific genetic variations may have altered immune responses that make them more susceptible to this form of tuberculosis. Genetic mutations in genes encoding surface receptors, adaptor proteins, kinases, transcription factors, nucleic receptors and other molecules involved in cellular interactions and molecular mechanisms have been associated with susceptibility to TB. Understanding the molecular mechanisms of immune interactions in host response to Mycobacterium tuberculosis is crucial to understanding the genetic dimension in susceptibility to tuberculosis, particularly its dreaded form of tuberculous meningitis. The aim of this update is to explore in details the key interactions between the main players in innate and adaptive immunity during infection with Mycobacterium tuberculosis, with particular emphasis on the genetic factors associated with susceptibility to tuberculosis, especially its dreaded form of tuberculous meningitis.
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- 2024
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14. Human Genetic and Immunological Determinants of SARS-CoV-2 Infection and Multisystem Inflammatory Syndrome in Children.
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Kholaiq H, Abdelmoumen Y, Moundir A, El Kettani A, Ailal F, Benhsaien I, Adnane F, Bourhanbour AD, Amenzoui N, El Bakkouri J, and Bousfiha AA
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces pneumonia and acute respiratory failure in Coronavirus Disease 2019 (COVID-19) patients with inborn errors of immunity to type I interferon (IFN-I). The impact of SARS-CoV-2 infection varies widely, ranging from mild respiratory symptoms to life-threatening illness and organ failure, with a higher incidence in men than in women. Approximately 3 to 5% of critical COVID-19 patients under 60 and a smaller percentage of elderly patients exhibit genetic defects in IFN-I production, including X-chromosome-linked TLR7 and autosomal TLR3 deficiencies. Around 15 to 20% of cases over 70 years old, and a smaller percentage of younger patients, present with preexisting autoantibodies neutralizing type I interferons. Additionally, innate errors affecting the control of the response to type I interferon have been associated with pediatric multisystem inflammatory syndrome (MIS-C). Several studies have described rare errors of immunity, such as XIAP deficiency, CYBB, SOCS1, OAS1/2, and RNASEL, as underlying factors in MIS-C susceptibility. However, further investigations in expanded patient cohorts are needed to validate these findings and pave the way for new genetic approaches to MIS-C. This review aims to present recent evidence from the scientific literature on genetic and immunological abnormalities predisposing individuals to critical SARS-CoV-2 infection through IFN-I. We will also discuss multisystem inflammatory syndrome in children (MIS-C). Understanding the immunological mechanisms and pathogenesis of severe COVID-19 may inform personalized patient care and population protection strategies against future serious viral infections., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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15. Impact of COVID-19 on child tuberculosis hospitalization.
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Zaidi S, Errami A, Belkhou I, Elkhaldi M, Ailal F, Benhsaien I, Adnane F, Amenzoui N, Abkari A, and Bousfiha AA
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- Humans, Child, Retrospective Studies, Morocco epidemiology, Female, Male, Child, Preschool, Adolescent, Quarantine, Tuberculosis, Pulmonary epidemiology, Infant, Hospitals, Pediatric statistics & numerical data, COVID-19 epidemiology, Hospitalization statistics & numerical data, Tuberculosis epidemiology
- Abstract
Introduction: Morocco has made remarkable progress in the fight against tuberculosis, but the Covid-19 pandemic has affected tuberculosis control worldwide, with notable fluctuations in tuberculosis epidemiology during and after the pandemic., Aim: To describe the impact of the Covid-19 pandemic on the rate of hospitalization for tuberculosis and its different localizations in children., Methods: We conducted a retrospective study based on the analysis of medical records of TB patients hospitalized within the Children's Hospital in Casablanca, during the periods before (2018-2019), during (2020) and after (2021-2022) Covid-19 quarantine., Results: Throughout the study period (2018-2022), the total number of patients hospitalized in our department was 7390, including 283 children were hospitalized for tuberculosis, with a mean age of 6 years. Before the Covid-19 pandemic, the average number of tuberculosis cases was 49 per year, of which the percentage of pulmonary tuberculosis was 32% and extra-pulmonary tuberculosis 68%. The number of cases was 23 per year during the quarantine period, with a percentage of pulmonary tuberculosis of 26% and extra-pulmonary tuberculosis of 74%. After the quarantine period, this number rose to 81 cases per year, of which 21% were pulmonary tuberculosis and 79% extrapulmonary tuberculosis (pleural tuberculosis was predominant in 44.1% of cases)., Conclusion: These results are consistent with data published by the World Health Organization, and with the findings of another study we carried out on the impact of COVID-19 on hospital admissions for acute lower respiratory tract infections. It is very likely that the reduction in the number of tuberculosis cases during the quarantine period is due to social distancing, which leads to a reduction in the transmission of tuberculosis between people as well as to the disruption of the national tuberculosis control program in Morocco, when positive cases are identified.
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- 2024
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16. An overview of risk factors in children with febrile seizures.
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Abbari I, Gueddari W, and Bousfiha AA
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- Child, Humans, Cytokines genetics, Risk Factors, Genetic Predisposition to Disease, Anti-Inflammatory Agents, Seizures, Febrile etiology, Seizures, Febrile genetics
- Abstract
Introduction: Febrile seizures (FS) are the most common neurologic disorder seen in children. Caused mainly by fever without any damage to the central nervous system (CNS). The associations of several factors, which we can find in the inflammatory response and genetic predisposition, are involved in the occurrence of FS., Aim: This review provides insight into risk factors, particularly the involvement of the inflammatory response and genetic susceptibility in the occurrence of FS., Methods: A PubMed search was performed using the keywords « febrile seizures », « inflammatory response », « Pro-inflammatory cytokines », «And anti-inflammatory cytokines ». The search strategy included meta-analyses, prospective case-control studies, clinical trials, observational studies, and reviews., Results: Febrile seizures with a peak incidence of 18 months usually occur between 6 months and 5 years. A variety of genetic, inflammatory, and environmental factors, including viruses and vaccines, trigger FS. A positive family history of febrile seizures increases the risk for FS occurrence with (20%) in siblings and (33%) in one parent. The involvement of inflammatory response genes, including the cytokine genes IL1B, IL1R, IL6, and IL4. According to these findings, FS is associated with the activation of a cascade of pro- and anti-inflammatory cytokines and the unbalance between these cytokines in the inflammation regulation plays a role in the development of FS., Conclusion: Current knowledge suggests that genetic susceptibility and inflammatory response dysregulation contribute to FS's genesis.
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- 2024
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17. Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children.
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Bastard P, Gervais A, Taniguchi M, Saare L, Särekannu K, Le Voyer T, Philippot Q, Rosain J, Bizien L, Asano T, Garcia-Prat M, Parra-Martínez A, Migaud M, Tsumura M, Conti F, Belot A, Rivière JG, Morio T, Tanaka J, Javouhey E, Haerynck F, Duvlis S, Ozcelik T, Keles S, Tandjaoui-Lambiotte Y, Escoda S, Husain M, Pan-Hammarström Q, Hammarström L, Ahlijah G, Abi Haidar A, Soudee C, Arseguel V, Abolhassani H, Sahanic S, Tancevski I, Nukui Y, Hayakawa S, Chrousos GP, Michos A, Tatsi EB, Filippatos F, Rodriguez-Palmero A, Troya J, Tipu I, Meyts I, Roussel L, Ostrowski SR, Schidlowski L, Prando C, Condino-Neto A, Cheikh N, Bousfiha AA, El Bakkouri J, Peterson P, Pujol A, Lévy R, Quartier P, Vinh DC, Boisson B, Béziat V, Zhang SY, Borghesi A, Pession A, Andreakos E, Marr N, Mentis AA, Mogensen TH, Rodríguez-Gallego C, Soler-Palacin P, Colobran R, Tillmann V, Neven B, Trouillet-Assant S, Brodin P, Abel L, Jouanguy E, Zhang Q, Martinón-Torres F, Salas A, Gómez-Carballa A, Gonzalez-Granado LI, Kisand K, Okada S, Puel A, Cobat A, and Casanova JL
- Subjects
- Child, Humans, Interferon-alpha, Autoantibodies, COVID-19, Interferon Type I
- Abstract
We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-α2 in 10 patients: IFN-α2 only in three, IFN-α2 plus IFN-ω in five, and IFN-α2, IFN-ω plus IFN-β in two; IFN-ω only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-α2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-ω in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-α2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-ω only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-ω and/or IFN-α2., (© 2024 Bastard et al.)
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- 2024
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18. An overview of a preliminary multicenter retrospective study on food and drug allergies in Moroccan pediatric population.
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Zidane Z, Chahine C, Mohtadi K, Chakroun A, Saïle R, Bousfiha AA, Rkain M, Chaer SE, Gueddari YE, Hbibi M, Daoudi LT, Benhsaien I, Elhafidi N, and Alj HS
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- Animals, Cattle, Child, Child, Preschool, Female, Humans, Allergens, Anti-Bacterial Agents, Multicenter Studies as Topic, Retrospective Studies, Drug Hypersensitivity, Food Hypersensitivity epidemiology, Food Hypersensitivity diagnosis, Food Hypersensitivity etiology, Urticaria
- Abstract
Introduction: this study aimed to investigate the prevalence and management of food allergies (FA) and drug allergies (DA) in Morocco. Sparse and conflicting epidemiological data exist on the exact prevalence of allergies in the country. The rise in allergies can be attributed to various factors., Methods: the study analyzed data from patients with suspected FA and DA who sought medical attention. Statistical tests were used to analyze the data, percentages were computed for qualitative variables, and for quantitative variables, medians or means accompanied by standard deviations (SD) were calculated. The Chi-square test was employed to assess categorical variables. A p-value < 0.05 was considered statistically significant., Results: Cow's milk was the most reported food allergen (58.2%), followed by egg and nuts (23.4% and 12.1%, respectively). The most affected age group was children under 5 years. Antibiotics were the leading cause of reported drug allergies (44.8%), particularly Beta-lactams. Immediate reactions were commonly associated with antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs). Symptoms of FA included acute urticaria, vomiting, anaphylactic shock, and facial edema. Urticaria was the most frequent symptom of DA. Antihistamines and corticosteroids were the main treatments used for both FA and DA., Conclusion: the prevalence of FA and DA in Morocco remains uncertain due to limited data. There is a need for centralized data collection and awareness among clinicians and the general population regarding allergies. The study highlights the importance of proper diagnosis and management of allergies to ensure patient safety. The findings emphasize the necessity of establishing a mandatory center for allergy care in Morocco to improve the understanding and management of allergic conditions., Competing Interests: The authors declare no competing interests., (Copyright: Zakaria Zidane et al.)
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- 2024
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19. Prevalence of celiac disease in Moroccan children with type 1 diabetes mellitus: A 16-year cross-sectional study.
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Belhiba O, Bousfiha AA, and Jennane F
- Abstract
Background: There is limited data available regarding the prevalence of celiac disease (CD) among children with type 1 diabetes mellitus (T1DM) in Arab countries and the Middle East. This cross-sectional study has been designed to explore the prevalence of CD specifically within the population of Moroccan children and adolescents diagnosed with type 1 diabetes mellitus (T1DM)., Patients and Methods: This is a cross-sectional study of patients who underwent regular follow-up for T1DM at the Pediatric Endocrinology Unit, Abderrahim Harouchi Children's University Hospital in Casablanca, over a 16-year period from 2004 to 2020. Patients were screened for CD by measuring anti-tissue transglutaminase IgA, and those with positive antibodies underwent endoscopy assessment., Results and Discussion: All 550 patients regularly followed up with TIDM were screened for CD. Fifty-five (33 girls/22 boys) of the screened patients had histologically documented CD, yielding a prevalence of 10%. Nineteen (41.9%) patients had developed CD within the initial four years of diagnosis with T1DM. Therefore, among the six confirmed CD patients, the average age at the onset of T1DM was 3.7 years. For twenty-four (57.5%) of the patients, exhibited no apparent clinical indications of CD, and their condition was only identified through systematic screening., Conclusion: This study showed a high prevalence rate of CD associated with type 1 diabetes T1DM, particularly among young children. The results of this paper indicate one of the highest prevalence rates reported in the existing literature for the coexistence of CD and T1DM. These findings may suggest the necessity of a systematic screening of CD in T1DM patients., Competing Interests: The authors declared that there were no competing interests., (© 2023 Belhiba, Bousfiha, Jennane, Licensee HBKU Press.)
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- 2024
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20. Autoimmune cytopenias in children: When to think of primary immunodeficiency?
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Hbibi M, El Alaoui El Hanafi M, Kasmi Z, Ouair H, Benmiloud S, Ailal F, Hida M, and Bousfiha AA
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- Child, Humans, Purpura, Thrombocytopenic, Idiopathic therapy, Purpura, Thrombocytopenic, Idiopathic drug therapy, Cytopenia, Anemia, Hemolytic, Autoimmune therapy, Anemia, Hemolytic, Autoimmune drug therapy, Thrombocytopenia diagnosis, Thrombocytopenia therapy
- Abstract
Autoimmune cytopenias are defined by autoantibodies' immune destruction of one or more blood elements. Most often it is autoimmune hemolytic anemia or immune thrombocytopenia or both that define Evans syndrome. It may be secondary to infection or to underlying pathology such as systemic autoimmune disease or primary immunodeficiency, especially when it becomes chronic over several years. Primary Immunodeficiencies or inborn errors of immunity (IEI) are no longer defined solely by infections: autoimmunity is part of the clinical features of several of these diseases. It is dominated by autoimmune cytopenias, in particular, immune thrombocytopenia (ITP) and autoimmune hemolytic anaemia (AIHA). The challenges for the clinician are the situations where autoimmune cytopenias are chronic, recurrent and/or refractory to the various long-term therapeutic options. Most of these therapies are similar in action and generally consist of non-mediated immune suppression or modulation. In these situations, primary Immunodeficiencies must be diagnosed as soon as possible to allow the initiation of a targeted treatment and to avoid several ineffective therapeutic lines.
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- 2024
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21. Hyperimmunoglobulinemia E and hereditary immune deficiencies.
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Fadil I, Ailal F, Beziat V, Casanova JL, Boisson B, and Bousfiha AA
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- Humans, Immunoglobulin E, Hypergammaglobulinemia, Hypersensitivity, Immunologic Deficiency Syndromes
- Abstract
The detection of a high serum immunoglobulin E (IgE) level is first suggestive of allergy, atopy or parasitosis. However, some very high values can be a sign of more severe diseases. We propose a diagnostic strategy based on clinical and biological data to identify the various hereditary immune diseases that also present with abnormally high serum IgE levels.
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- 2023
22. Mendelian susceptibility to mycobacterial diseases: State of the puzzle.
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Errami A and Bousfiha AA
- Abstract
The constant progress of genomics and the establishment of new functional tests have paved the way for identifying monogenic defects conferring a selective predisposition to infections by certain microbes as a new type of inborn errors of immunity (IEIs). Mendelian susceptibility to mycobacterial diseases (MSMD) is the most characterized of these IEIs, with 36 different disorders found in 20 distinct genes ( IFNGR1, IFNGR2, IFNG, IL12RB1, IL12RB2, IL23R, IL12B, ISG15, USP18, ZNFX1, TBX21, STAT1, TYK2, IRF8, IRF1, CYBB, JAK1, RORC, NEMO , and SPPL2A ) over the last 20 years. MSMD confers a selective susceptibility to infections with weakly virulent mycobacteria, including the M . bovis Bacille Calmette-Guerin (BCG) vaccines and various environmental mycobacteria in patients, primarily children, without classical immune defects. These patients may also present severe forms of tuberculosis, and about half of them might develop non-typhoidal salmonellosis. In some cases, patients also suffer from chronic mucocutaneous candidiasis (CMC), while in others, patients also present severe viral, parasitic, fungal, and/or bacterial diseases. Despite this clinical and genetic heterogeneity, almost all genetic etiologies of MSMD alter the interferon-gamma (IFN-γ)- mediated immunity by impairing or abolishing IFN-γ production or the response to this cytokine. It was proven that the human IFN-γ level is a quantitative trait that defines the outcome of mycobacterial infection. The study of these monogenic defects contributes to understanding the molecular mechanism of mycobacterial diseases in humans and to the development of new diagnostic and therapeutic approaches to improve care and prognosis. For example, MSMD patients with impaired production of IFN-γ may benefit from injections of human recombinant IFN-γ, while for patients with abolished response to this cytokine, hematopoietic stem cell transplantation (HSCT) and promising gene therapy are the only current therapeutic options. These discoveries also bridge the gap between simple Mendelian inheritance and complex human genetics., (© 2023 Errami, Bousfiha, HBKU Press.)
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- 2023
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23. Classification of common variable immunodeficiency through immunological and clinical phenotyping in Moroccan patients.
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Mokhantar K, Allaoui A, Ailal F, Bakkouri JE, Ouazahrou K, Errami A, Bousfiha AA, and Moudatir M
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Objective: Common variable immunodeficiency (CVID) is a complex inborn error of humoral immunity with complications of both infectious and non-infectious origins. Classifications of CVID patients provide a clearer understanding of the pathogenesis, prediction, and management of non-infectious complications. This study aims to classify Moroccan CVID patients based on the European classification (EUROclass). Materials and Methods: We recruited 20 CVID patients meeting standard diagnostic criteria (5-6). After collecting clinical and demographic data, we used flow cytometry to analyze B-cell subsets and group patients and assess the relation of each group with clinical manifestations. Results: 90% of the patients in our cohort study had a history of respiratory infections. The noninfectious manifestations included splenomegaly, autoimmunity, lymphadenopathy, and granulomatous diseases diagnosed in 50%, 45%, 40%, and 25% of patients, respectively. We observed significant co-occurrence of splenomegaly with autoimmunity and granulomatous diseases to a lesser extent. Patients had a significant reduction in total, switched memory, marginal zone-like, plasma blasts, and a substantial increase in the percentage of activated B cells, suggesting a defect in the late phases of B-cell differentiation. This condition was linked with an increased occurrence of splenomegaly and granulomatous affections. Besides, patients also had an expansion of CD21low B-cells, which was strongly associated with splenomegaly. Conclusion: The classification of the first Moroccan cohort of CVID patients showed agreement with previous results. It suggests the possibility of adopting this approach on a global scale for better diagnosis and follow-up of CVID patients., (© 2023 Mokhantar, Allaoui, Ailal, El Bakkouri, Ouazahrou, Errami, Bousfiha, Moudatir, licensee HBKU Press.)
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- 2023
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24. Efficacy of Anakinra Treatment in two Moroccan Patients With Mevalonate Kinase Deficiency.
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Souali M, Sakhi A, Bousfiha AA, and Bouayed K
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Mevalonate kinase deficiency (MKD) is a rare hereditary autoinflammatory disease, with a widely variable clinical spectrum. It is characterized by febrile recurrent episodes and systemic inflammation. Data on therapeutic options for MKD are still limited and remain unknown in our country. We report Moroccan cases with MKD referred in our unit and treated with Anakinra, an interleukin-1 receptor antagonist. Through this study, we evaluate the efficacy of this bioagent, in our 2 MKD patients, in whom Anakinra has shown a complete clinical remission, with a remaining mild inflammation for one case, and normalization of growth with rare episodes of cervical adenopathies for the second case. Our experience provides an additional argument supporting the efficacy of Anakinra treatment, demonstrated previously but still lacks of objective data., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)
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- 2023
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25. Diagnostic guidance for hereditary neutropenia in children: Narrative literature review.
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Kasmi Z, El Bakkouri J, Ailal F, Oukkache B, Donadieu J, and Bousfiha AA
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- Child, Humans, Congenital Bone Marrow Failure Syndromes, Phenotype, Physical Examination, Neutropenia etiology, Neutropenia genetics, Neutropenia congenital
- Abstract
In the era of genomics, orientation in the face of hereditary neutropenia still requires, first and foremost, a good clinical and cytological analysis. The thirty responsible genes now explain 60% of congenital neutropenia. These are rare since they are only found in 1‰ of all congenital neutropenia, estimated at 1% of the population. The clinical examination looks for phenotypes associated with syndromic hereditary neutropenia and cytology will guide this etiological research thanks to the data collected from blood count and bone marrow analysis. The objective of this narrative literature review is to provide an overview of the most recent literature regarding acquired and congenital chronic neutropenia and will provide a decision tree to guide towards aetiology. This will allow a better discussion with geneticists even if the genotype-phenotype correlation is not very strong.
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- 2023
26. Atypical Cutaneous Viral Infections Reveal an Inborn Error of Immunity in 8 Patients.
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El Kettani A, Ailal F, Marnissi F, Hali F, El Bakkouri J, Benhsaien I, Le Voyer T, Guèye MS, Chevalier R, Chiheb S, Zerouali K, Jouanguy E, Casanova JL, and Bousfiha AA
- Abstract
Unusual viral skin infections might be the first clinical manifestation in children with an inborn error of immunity (IEI). We performed a prospective study from 1 October 2017 to 30 September 2021, at the Department of Pediatric Infectious Diseases and Clinical Immunity of Ibn Rochd University Hospital-Casablanca. During this period, on 591 patients newly diagnosed with a probable IEI, eight of them (1.3%), from six independent families, had isolated or syndromic unusual viral skin infections, which were either profuse, chronic or recurrent infections, and resistant to any treatment. The median age of disease onset was nine years old and all patients were born from a first-degree consanguineous marriage. By combining clinical, immunological and genetic investigations, we identified GATA2 deficiency in one patient with recalcitrant profuse verrucous lesions and monocytopenia (1/8) and STK4 deficiency in two families with HPV lesions, either flat or common warts, and lymphopenia (2/8), as previously reported. We also identified COPA deficiency in twin sisters with chronic profuse Molluscum contagiosum lesions, pulmonary diseases and microcytic hypochromic anemia (2/8). Finally, we also found one patient with chronic profuse MC lesions and hyper IgE syndrome, (1/8) and two patients with either recalcitrant profuse verrucous lesions or recurrent post-herpetic erythema multiforme and a combined immunodeficiency (2/8) with no genetic defect identified yet. Raising clinicians awareness that infectious skin diseases might be the consequence of an inborn error of immunity would allow for optimized diagnosis, prevention and treatment of patients and their families.
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- 2023
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27. Mendelian Susceptibility to Mycobacterial Disease (MSMD): Clinical, Immunological, and Genetic Features of 22 Patients from 15 Moroccan Kindreds.
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Errami A, Baghdadi JE, Ailal F, Benhsaien I, Bakkouri JE, Jeddane L, Rada N, Benajiba N, Mokhantar K, Ouazahrou K, Zaidi S, Abel L, Casanova JL, Boisson-Dupuis S, Bustamante J, and Bousfiha AA
- Subjects
- Infant, Newborn, Humans, Child, Preschool, Genetic Predisposition to Disease, BCG Vaccine, Interleukin-12, Mutation genetics, Mycobacterium Infections etiology, Tuberculosis genetics, Mycobacterium
- Abstract
Purpose: The first molecular evidence of a monogenic predisposition to mycobacteria came from the study of Mendelian susceptibility to mycobacterial disease (MSMD). We aimed to study this Mendelian susceptibility to mycobacterial diseases in Moroccan kindreds through clinical, immunological, and genetic analysis., Methods: Patients presented with clinical features of MSMD were recruited into this study. We used whole blood samples from patients and age-matched healthy controls. To measure IL-12 and IFN-γ production, samples were activated by BCG plus recombinant human IFN-γ or recombinant human IL-12. Immunological assessments and genetic analysis were also done for patients and their relatives., Results: Our study involved 22 cases from 15 unrelated Moroccan kindreds. The average age at diagnosis is 4 years. Fourteen patients (64%) were born to consanguineous parents. All patients were vaccinated with the BCG vaccine, and twelve of them (55%) developed locoregional or disseminated BCG infections. The other symptomatic patients had severe tuberculosis and/or recurrent salmonellosis. Genetic mutations were identified on the following genes: IL12RB1 in 8 patients, STAT1 in 7 patients; SPPL2A, IFNGR1, and TYK2 in two patients each; and TBX21 in one patient, with different modes of inheritance. All identified mutations/variants altered production or response to IFN-γ or both., Conclusion: Severe forms of tuberculosis and complications of BCG vaccination may imply a genetic predisposition present in the Moroccan population. In the presence of these infections, systematic genetic studies became necessary. BCG vaccination is contraindicated in MSMD patients and should be delayed in newborn siblings until the exclusion of a genetic predisposition to mycobacteria., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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28. Clinical and serological correlation of systemic sclerosis in Moroccan patients.
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Ouazahrou K, El Bakkouri J, Souali M, Jeddane L, Mokhantar K, Errami A, El Kabli H, Bousfiha AA, and Echchilali K
- Abstract
Objective: SSc is a CTD characterized by excessive fibrosis of the skin and internal organs, along with microvascular damage, and is often associated with typical autoantibodies. The aim of this study was to analyse the correlation between specific autoantibody profiles, clinical and paraclinical features in Moroccan patients with SSc., Methods: We analysed the presence of specific autoantibodies in 46 SSc patients using IIF on HEp-2 cells and immunodot. We then correlated the types of autoantibodies with clinical and laboratory manifestations., Results: Among our patients, 86.9% were females. The mean age of patients at diagnosis was 50.21 years, with an average delay to diagnosis of 5 years. The main clinical manifestations found were RP (89.2%), sclerodactyly (84.8%), proximal scleroderma (67.4%), gastrointestinal involvement (50%) and interstitial lung disease (30.4%). According to the specific autoantibody profile, 14 patients were anti-topo I positive (30.4%), 8 anti-RNP (68 kDa/A/C) positive (17.4%) and 6 anti-RNA polymerase III positive (13%). We found a significant association of anti-RNA polymerase III with sclerodactyly and pulmonary arterial hypertension ( P < 0.05). We also found an association between anti-topo I and interstitial lung disease in 30.4% of patients. There was no significant association between the positivity for the autoantibodies and other diagnosed clinical manifestations., Conclusion: Some clinical manifestations of SSc might be positively correlated with the presence of specific autoantibodies. Environmental factors, ethnicity and gene interaction might also influence this correlation., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
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- 2023
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29. Effectiveness of natural immune protection against COVID-19 reinfection: systematic review with meta-analysis.
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Moundir A, Errami A, El Bakkouri J, Ben Abdelaziz A, and Bousfiha AA
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- Humans, SARS-CoV-2, Pandemics, Reinfection epidemiology, Reinfection prevention & control, COVID-19 epidemiology, COVID-19 prevention & control
- Abstract
Introduction: The future of the COVID-19 pandemic depends on the evolution of the virus and immune protection stimulated by vaccination or upon exposure to natural infection. While most research focuses on vaccine efficacy, data remain unclear on the efficacy and duration of natural immune protection against infection., Aim: In this article, we aim to determine the efficacy of natural immune protection against reinfection with COVID-19 or severe COVID-19., Methods: We performed a systematic review of available studies in electronic databases followed by a meta-analysis to determine the efficacy of natural immune protection against COVID-19 reinfection and severe infection., Results: Of the 414 studies identified for the full review, 8 studies met the inclusion criteria and were analyzed. The total number of individuals participating in the 8 studies included 19,837,147 people. Individuals with a history of SARS-CoV-2 infection (1,9% [0,6%-3,1%]) had a lower rate of infection than individuals without a history of infection (7,1% [3,9%-10,1%]). The mean efficacy of natural immune protection against reinfection was 84,7% [78,5%-90,9%], while the mean efficacy of natural immune protection against severe COVID-19 infection was 96,9% [94%-99,6%]., Conclusion: These results indicate that natural immune protection against reinfection is high, particularly against severe COVID-19. However, further research is needed to determine the duration of natural immune protection and the impact of different variants of SARS-CoV-2.
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- 2023
30. Genetic Diagnosis of Inborn Errors of Immunity in an Emerging Country: a Retrospective Study of 216 Moroccan Patients.
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Moundir A, Ouair H, Benhsaien I, Jeddane L, Rada N, Amenzoui N, Jouhadi Z, Adnane F, Hafidi NE, Kili A, Bourhanbour Drissi A, Babakhouya A, Benmiloud S, Hbibi M, Benajiba N, Hida M, Bouskraoui M, Mahraoui C, Admou B, Bakkouri JE, Ailal F, and Bousfiha AA
- Subjects
- Humans, Retrospective Studies, Mutation genetics, Hereditary Complement Deficiency Diseases, Morocco epidemiology, Genetic Testing
- Abstract
Purpose: Genetic testing provides great support to validate the clinical diagnosis of inborn errors of immunity (IEI). However, the high cost and advanced technology make these tests inaccessible to a large proportion of patients in low-income countries. In the present study, we aim to evaluate the Moroccan experience in genetic testing and to report the main molecular features and difficulties encountered in genetic diagnosis., Methods: We performed a multi-center retrospective analysis of all patients with a molecular diagnosis and registered in the national registry between 2010 and 2022. To estimate the impact of the newly identified mutations, we calculated the Combined Annotation Dependent Depletion (CADD) score and the mutation significance cutoff (MSC) for each variant., Results: A total of 216 (29%) patients received a genetic diagnosis out of 742 patients with IEI included in the registry. All genetic tests were performed in the context of thesis projects (40%) or international collaborations (60%). A set of 55 genetic defects were identified, including 7 newly reported: SNORA31, TBX21, SPPL2A, TYK2, RLTPR, ZNF341, and STAT2 GOF. Genetic diagnoses were more frequent in the defects of innate and intrinsic immunity with a percentage of 78%, while antibody deficiencies had a lower frequency with a percentage of 17.5%. Only one genetic diagnosis has been made in the complement deficiency group. The most commonly used molecular techniques were Sanger sequencing (37%) followed by targeted gene sequencing (31%)., Conclusion: The thesis projects and collaborations were beneficial as they allowed us to provide a definitive genetic diagnosis to 29% of the patients and to contribute to the identification of new genetic defects and mutations. These results offer insight into the progress made in genetic diagnoses of IEI in Morocco, which would provide a baseline for improving the clinical management of patients with IEI., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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31. Spectrum of auto-inflammatory diseases in Morocco: a monocentric experience.
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Souali M, Sakhi A, Benbrahim Ansari G, Mikou N, Bousfiha AA, and Bouayed K
- Abstract
Objective: Auto-inflammatory diseases (AIDs) result from mutations in genes of the innate immune system leading to periodic multisystemic inflammation. We aimed to describe the clinical, biological and molecular features (when available) and outcomes of Moroccan patients with AIDs., Methods: Patient data were collected retrospectively and analysed over a 13-year period., Results: Among 30 patients, 60% had FMF, 16% mevalonate kinase deficiency (MKD) and 24% other AIDs. The mean age at first consultation was 6.9 years, and the mean diagnostic delay was 3 years. Consanguinity was reported in 16 cases. IgA vasculitis was associated with 33% of FMF patients, in whom the main clinical features were fever (88.8%), abdominal pain (100%), arthralgias (88.8%) and arthritis (50%), and the most frequent mutation was M694V (66%). All FMF patients were treated with colchicine. Most MKD patients were confirmed by elevated urinary mevalonic acid levels, and four of five MKD patients received targeted therapy. Chronic recurrent osteomyelitis patients were confirmed by radiological and histological analysis. Two cases of Marshall syndrome were diagnosed according to validated criteria. A case of familial pustular psoriasis was diagnosed based on histological analysis and a patient with Muckle-Wells syndrome by clinical features. The outcome was favourable in 76%, partial in 13%, and three deaths were reported., Conclusion: FMF and MKD are the most reported diseases. AIDs are probably underestimated because they are unknown to clinicians. The aim of this work is to raise awareness among paediatricians about AIDs and create a network for best practice., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
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- 2023
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32. Student's attitudes towards medical education in Arabic (Morocco 2020).
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Ameayou S, Ouali M, Hassoune S, Ben Abdelaziz A, and Bousfiha AA
- Subjects
- Humans, Morocco, Students, Attitude, Language, Education, Medical
- Abstract
Introduction: Several studies suggest that teaching medicine in the national language is essential for quality training and for communication with patients., Aim and Methods: To measure the students' level of understanding of their French language training and skills acquisition, as well as the difficulties they encounter in communicating with patients and their families, and the extent to which they accept medical studies in Arabic, we conducted a descriptive crosssectional study on a random sample of 450 students from the Faculty of Medicine and Pharmacy of Casablanca., Results: 16% of the students had trouble assimilating their lessons in French, 48.9% of them had trouble communicating with the patient, and 22% were ready to study medicine in Arabic. Regarding the effect of teaching medicine in Arabic on different fields, 42.2% of the students mentioned a positive effect on the training, 85.2% on the communication with the patient during their training on field and 64.8% on the quality of care., Conclusion: Our study revealed the existence of multiple difficulties among students, particularly in the field of communication with the patient, which is a fundamental pillar for the quality of health care, hence the need to provide effective and rapid solutions to the problem of language in medical education.
- Published
- 2023
33. [Autoimmune lymphoproliferative syndrome: a case report].
- Author
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Youssif HB, Ailal F, Benhsaien I, Bakkouri JE, Jeddane L, Maani KE, and Bousfiha AA
- Subjects
- Humans, Splenomegaly etiology, Sirolimus, Immunosuppressive Agents therapeutic use, Autoimmune Lymphoproliferative Syndrome diagnosis, Autoimmune Lymphoproliferative Syndrome genetics, Autoimmune Lymphoproliferative Syndrome therapy, Autoimmune Diseases, Pancytopenia
- Abstract
Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder of lymphocyte homeostasis, resulting from mutations in the Fas apoptotic pathway. It is characterized by non-infectious and non-malignant chronic lymphoproliferation and an increased risk of lymphoid malignancy. The diagnosis of this condition usually combines chronic lymphadenopathy and/or splenomegaly exceeding 6 months, autoimmune cytopenias, with an elevated level of CD3+CD4-CD8- Tαβ lymphocytes, known as "double-negative" T cells. Differential diagnosis includes infections, autoimmune diseases or malignancies. Although clinical examination and laboratory tests are highly suggestive, this disease goes widely unrecognized. We here report, for the first time, the case of ALPS, a Moroccan patient, and aged 8 years, with recurrent fever, splenomegaly and adenopathies. Paraclinical examinations revealed chronic pancytopenia, higher than normal TαÎ
2 double negative lymphocytes, hypergammaglobulinemia, and elevated serum levels of soluble FAS ligand. The diagnosis of ALPS was made. First-line treatment included corticosteroids and immunoglobulins. Then the patient received mycophenolate followed by Sirolimus. This treatment resulted in better clinical and laboratory tests results. Our aim is to raise awareness of this rare condition, which may be under-diagnosed, among physicians., Competing Interests: Les auteurs ont déclaré qu´ils n´ont aucun conflit d´intérêts., (Copyright: Houda Ben Youssif et al.)- Published
- 2022
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34. Impaired IL-23-dependent induction of IFN-γ underlies mycobacterial disease in patients with inherited TYK2 deficiency.
- Author
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Ogishi M, Arias AA, Yang R, Han JE, Zhang P, Rinchai D, Halpern J, Mulwa J, Keating N, Chrabieh M, Lainé C, Seeleuthner Y, Ramírez-Alejo N, Nekooie-Marnany N, Guennoun A, Muller-Fleckenstein I, Fleckenstein B, Kilic SS, Minegishi Y, Ehl S, Kaiser-Labusch P, Kendir-Demirkol Y, Rozenberg F, Errami A, Zhang SY, Zhang Q, Bohlen J, Philippot Q, Puel A, Jouanguy E, Pourmoghaddas Z, Bakhtiar S, Willasch AM, Horneff G, Llanora G, Shek LP, Chai LYA, Tay SH, Rahimi HH, Mahdaviani SA, Nepesov S, Bousfiha AA, Erdeniz EH, Karbuz A, Marr N, Navarrete C, Adeli M, Hammarstrom L, Abolhassani H, Parvaneh N, Al Muhsen S, Alosaimi MF, Alsohime F, Nourizadeh M, Moin M, Arnaout R, Alshareef S, El-Baghdadi J, Genel F, Sherkat R, Kiykim A, Yücel E, Keles S, Bustamante J, Abel L, Casanova JL, and Boisson-Dupuis S
- Subjects
- Humans, Interferon-gamma metabolism, Interleukin-23, Job Syndrome genetics, TYK2 Kinase deficiency, TYK2 Kinase genetics, TYK2 Kinase metabolism
- Abstract
Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-α/β (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the common P1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isolated mycobacterial disease). We report three new forms of TYK2 deficiency in six patients from five families homozygous for rare TYK2 alleles (R864C, G996R, G634E, or G1010D) or compound heterozygous for P1104A and a rare allele (A928V). All these missense alleles encode detectable proteins. The R864C and G1010D alleles are hypomorphic and loss-of-function (LOF), respectively, across signaling pathways. By contrast, hypomorphic G996R, G634E, and A928V mutations selectively impair responses to IL-23, like P1104A. Impairment of the IL-23-dependent induction of IFN-γ is the only mechanism of mycobacterial disease common to patients with complete TYK2 deficiency with or without TYK2 expression, partial TYK2 deficiency across signaling pathways, or rare or common partial TYK2 deficiency specific for IL-23 signaling., (© 2022 Ogishi et al.)
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- 2022
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35. Inborn errors of immunity and related microbiome.
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Hazime R, Eddehbi FE, El Mojadili S, Lakhouaja N, Souli I, Salami A, M'Raouni B, Brahim I, Oujidi M, Guennouni M, Bousfiha AA, and Admou B
- Subjects
- Dysbiosis, Humans, Immunoglobulin A, Receptors, Interleukin-10, Gastrointestinal Microbiome, Immune System Diseases genetics, Immune System Diseases microbiology
- Abstract
Inborn errors of immunity (IEI) are characterized by diverse clinical manifestations that are dominated by atypical, recurrent, chronic, or severe infectious or non-infectious features, including autoimmunity, lymphoproliferative disease, granulomas, and/or malignancy, which contribute substantially to morbidity and mortality. Some data suggest a correlation between clinical manifestations of IEI and altered gut microbiota. Many IEI display microbial dysbiosis resulting from the proliferation of pro-inflammatory bacteria or a decrease in anti-inflammatory bacteria with variations in the composition and function of numerous microbiota. Dysbiosis is considered more established, mainly within common variable immunodeficiency, selective immunoglobulin A deficiency, severe combined immunodeficiency diseases, Wiskott-Aldrich syndrome, Hyper-IgE syndrome, autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED), immune dysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) syndrome, IL-10 receptor deficiency, chronic granulomatous disease, and Kostmann disease. For certain IEIs, the specific predominance of gastrointestinal, respiratory, and cutaneous involvement, which is frequently associated with dysbiosis, justifies the interest for microbiome identification. With the better understanding of the relationship between gut microbiota, host immunity, and infectious diseases, the integration of microbiota modulation as a therapeutic approach or a preventive measure of infection becomes increasingly relevant. Thus, a promising strategy is to develop optimized prebiotics, probiotics, postbiotics, and fecal microbial transplantation to rebalance the intestinal microbiota and thereby attenuate the disease activity of many IEIs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hazime, Eddehbi, El Mojadili, Lakhouaja, Souli, Salami, M’Raouni, Brahim, Oujidi, Guennouni, Bousfiha and Admou.)
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- 2022
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36. When to suspect an immune deficiency in adults?
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Allaoui A, Mokhantar K, Jeddane L, Ailal F, Elkabli H, Bousfiha AA, and Moudatir M
- Subjects
- Male, Humans, Referral and Consultation, Immunologic Deficiency Syndromes diagnosis
- Abstract
Immune deficiencies in adults are quite common conditions in medical practice. However, they present with different clinical phenotypes, whether primary or secondary, which makes their diagnosis more tedious, hence diagnostic and management delays. Through this update, we will review the most common immune deficiencies, their presentations and features. This update's main aim was to propose to the practitioner a structured clinical reasoning and approach, in order to suspect an immune deficiency and initiate a guided exploration. It will also be easier for him to know when a referral to the specialist is necessary.
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- 2022
37. HPV-Related Skin Phenotypes in Patients with Inborn Errors of Immunity.
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El Kettani A, Ailal F, El Bakkouri J, Zerouali K, Béziat V, Jouanguy E, Casanova JL, and Bousfiha AA
- Abstract
Patients with inborn errors of immunity (IEI) are prone to develop infections, either due to a broad spectrum of pathogens or to only one microbe. Since skin is a major barrier tissue, cutaneous infections are among the most prevalent in patients with IEI due to high exposures to many microbes. In the general population, human papillomaviruses (HPVs) cause asymptomatic or self-healing infections, but, in patients with IEI, unusual clinical expression of HPV infection is observed ranging from epidermodysplasia verruciformis (EV) (a rare disease due to β-HPVs) to profuse, persistent, and recalcitrant warts (due to α-, γ-, and μ-HPVs) or even tree man syndrome (due to HPV2). Mutations in EVER1, EVER2, and CIB1 are associated with EV phenotype; GATA2, CXCR4, and DOCK8 mutations are typically associated with extensive HPV infections, but there are several other IEI that are less frequently associated with severe HPV lesions. In this review, we describe clinical, immunological, and genetic patterns of IEI related to severe HPV cutaneous infections and propose an algorithm for diagnosis of IEI with severe warts associated, or not, with lymphopenia.
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- 2022
- Full Text
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38. The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.
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Manry J, Bastard P, Gervais A, Le Voyer T, Rosain J, Philippot Q, Michailidis E, Hoffmann HH, Eto S, Garcia-Prat M, Bizien L, Parra-Martínez A, Yang R, Haljasmägi L, Migaud M, Särekannu K, Maslovskaja J, de Prost N, Tandjaoui-Lambiotte Y, Luyt CE, Amador-Borrero B, Gaudet A, Poissy J, Morel P, Richard P, Cognasse F, Troya J, Trouillet-Assant S, Belot A, Saker K, Garçon P, Rivière JG, Lagier JC, Gentile S, Rosen LB, Shaw E, Morio T, Tanaka J, Dalmau D, Tharaux PL, Sene D, Stepanian A, Mégarbane B, Triantafyllia V, Fekkar A, Heath JR, Franco JL, Anaya JM, Solé-Violán J, Imberti L, Biondi A, Bonfanti P, Castagnoli R, Delmonte OM, Zhang Y, Snow AL, Holland SM, Biggs CM, Moncada-Vélez M, Arias AA, Lorenzo L, Boucherit S, Anglicheau D, Planas AM, Haerynck F, Duvlis S, Ozcelik T, Keles S, Bousfiha AA, El Bakkouri J, Ramirez-Santana C, Paul S, Pan-Hammarström Q, Hammarström L, Dupont A, Kurolap A, Metz CN, Aiuti A, Casari G, Lampasona V, Ciceri F, Barreiros LA, Dominguez-Garrido E, Vidigal M, Zatz M, van de Beek D, Sahanic S, Tancevski I, Stepanovskyy Y, Boyarchuk O, Nukui Y, Tsumura M, Vidaur L, Tangye SG, Burrel S, Duffy D, Quintana-Murci L, Klocperk A, Kann NY, Shcherbina A, Lau YL, Leung D, Coulongeat M, Marlet J, Koning R, Reyes LF, Chauvineau-Grenier A, Venet F, Monneret G, Nussenzweig MC, Arrestier R, Boudhabhay I, Baris-Feldman H, Hagin D, Wauters J, Meyts I, Dyer AH, Kennelly SP, Bourke NM, Halwani R, Sharif-Askari FS, Dorgham K, Sallette J, Sedkaoui SM, AlKhater S, Rigo-Bonnin R, Morandeira F, Roussel L, Vinh DC, Erikstrup C, Condino-Neto A, Prando C, Bondarenko A, Spaan AN, Gilardin L, Fellay J, Lyonnet S, Bilguvar K, Lifton RP, Mane S, Anderson MS, Boisson B, Béziat V, Zhang SY, Andreakos E, Hermine O, Pujol A, Peterson P, Mogensen TH, Rowen L, Mond J, Debette S, de Lamballerie X, Burdet C, Bouadma L, Zins M, Soler-Palacin P, Colobran R, Gorochov G, Solanich X, Susen S, Martinez-Picado J, Raoult D, Vasse M, Gregersen PK, Piemonti L, Rodríguez-Gallego C, Notarangelo LD, Su HC, Kisand K, Okada S, Puel A, Jouanguy E, Rice CM, Tiberghien P, Zhang Q, Casanova JL, Abel L, and Cobat A
- Subjects
- Adult, Age Factors, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Risk, Antibodies, Neutralizing blood, Autoantibodies blood, Autoimmunity, COVID-19 immunology, COVID-19 mortality, Interferon Type I immunology, SARS-CoV-2
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
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- 2022
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39. [Genetic basis of common variable immunodeficiency: from common to variable].
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Allaoui A, Mokhantar K, Jeddane L, Dehbi H, Ailal F, Bousfiha AA, Elkabli H, and Moudatir M
- Subjects
- Genetic Predisposition to Disease, Genomics, High-Throughput Nucleotide Sequencing, Humans, Precision Medicine, Common Variable Immunodeficiency diagnosis, Common Variable Immunodeficiency genetics
- Abstract
Common variable immunodeficiency (CVID) is one of the most prevalent primary immunodeficiencies. It is characterized by hypogammaglobulinaemia, increased susceptibility to infections and impaired vaccine responses. CVID has an important, clinical, immunological and genetic heterogeneity. A minority of patients present with monogenic forms in CVID, unlike other primary immunodeficiencies. With the development of new technologies in genetics, including next generation sequencing, the number of identified genes in CVID is increasing. Therefore, CVID is now considered as an umbrella disease, gathering distinct pathological entities. It is currently recognized that CVID is a complex polygenic rather than a monogenic syndrome. A multi-omic approach combining genomics, epigenetics and proteomics will shed light on CVID complex pathophysiology, which still enigmatic. This integrative approach will also offer more targeted therapies, and therefore a personalized medicine. This review aims to discuss current knowledge concerning the genetic and molecular bases of CVID as well as their application in clinical practice.
- Published
- 2021
- Full Text
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40. Inherited human c-Rel deficiency disrupts myeloid and lymphoid immunity to multiple infectious agents.
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Lévy R, Langlais D, Béziat V, Rapaport F, Rao G, Lazarov T, Bourgey M, Zhou YJ, Briand C, Moriya K, Ailal F, Avery DT, Markle J, Lim AI, Ogishi M, Yang R, Pelham S, Emam M, Migaud M, Deswarte C, Habib T, Saraiva LR, Moussa EA, Guennoun A, Boisson B, Belkaya S, Martinez-Barricarte R, Rosain J, Belkadi A, Breton S, Payne K, Benhsaien I, Plebani A, Lougaris V, Di Santo JP, Neven B, Abel L, Ma CS, Bousfiha AA, Marr N, Bustamante J, Liu K, Gros P, Geissmann F, Tangye SG, Casanova JL, and Puel A
- Subjects
- Adaptive Immunity genetics, Adaptive Immunity immunology, Child, Consanguinity, Female, Hematopoietic Stem Cell Transplantation, Homozygote, Host Microbial Interactions genetics, Host Microbial Interactions immunology, Humans, Immunity, Innate genetics, Immunity, Innate immunology, Lymphocyte Activation, Lymphocytes classification, Lymphocytes immunology, Mutation, Myeloid Cells immunology, Primary Immunodeficiency Diseases therapy, Protein Isoforms, Genes, rel, Primary Immunodeficiency Diseases genetics, Primary Immunodeficiency Diseases immunology, Proto-Oncogene Proteins c-rel deficiency, Proto-Oncogene Proteins c-rel genetics
- Abstract
We studied a child with severe viral, bacterial, fungal, and parasitic diseases, who was homozygous for a loss-of-function mutation of REL, encoding c-Rel, which is selectively expressed in lymphoid and myeloid cells. The patient had low frequencies of NK, effector memory cells reexpressing CD45RA (Temra) CD8+ T cells, memory CD4+ T cells, including Th1 and Th1*, Tregs, and memory B cells, whereas the counts and proportions of other leukocyte subsets were normal. Functional deficits of myeloid cells included the abolition of IL-12 and IL-23 production by conventional DC1s (cDC1s) and monocytes, but not cDC2s. c-Rel was also required for induction of CD86 expression on, and thus antigen-presenting cell function of, cDCs. Functional deficits of lymphoid cells included reduced IL-2 production by naive T cells, correlating with low proliferation and survival rates and poor production of Th1, Th2, and Th17 cytokines by memory CD4+ T cells. In naive CD4+ T cells, c-Rel is dispensable for early IL2 induction but contributes to later phases of IL2 expression. The patient's naive B cells displayed impaired MYC and BCL2L1 induction, compromising B cell survival and proliferation and preventing their differentiation into Ig-secreting plasmablasts. Inherited c-Rel deficiency disrupts the development and function of multiple myeloid and lymphoid cells, compromising innate and adaptive immunity to multiple infectious agents.
- Published
- 2021
- Full Text
- View/download PDF
41. Autoantibodies neutralizing type I IFNs are present in ~ 4% of uninfected individuals over 70 years old and account for ~ 20% of COVID-19 deaths.
- Author
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Bastard P, Gervais A, Le Voyer T, Rosain J, Philippot Q, Manry J, Michailidis E, Hoffmann HH, Eto S, Garcia-Prat M, Bizien L, Parra-Martínez A, Yang R, Haljasmägi L, Migaud M, Särekannu K, Maslovskaja J, de Prost N, Tandjaoui-Lambiotte Y, Luyt CE, Amador-Borrero B, Gaudet A, Poissy J, Morel P, Richard P, Cognasse F, Troya J, Trouillet-Assant S, Belot A, Saker K, Garçon P, Rivière JG, Lagier JC, Gentile S, Rosen LB, Shaw E, Morio T, Tanaka J, Dalmau D, Tharaux PL, Sene D, Stepanian A, Megarbane B, Triantafyllia V, Fekkar A, Heath JR, Franco JL, Anaya JM, Solé-Violán J, Imberti L, Biondi A, Bonfanti P, Castagnoli R, Delmonte OM, Zhang Y, Snow AL, Holland SM, Biggs C, Moncada-Vélez M, Arias AA, Lorenzo L, Boucherit S, Coulibaly B, Anglicheau D, Planas AM, Haerynck F, Duvlis S, Nussbaum RL, Ozcelik T, Keles S, Bousfiha AA, El Bakkouri J, Ramirez-Santana C, Paul S, Pan-Hammarström Q, Hammarström L, Dupont A, Kurolap A, Metz CN, Aiuti A, Casari G, Lampasona V, Ciceri F, Barreiros LA, Dominguez-Garrido E, Vidigal M, Zatz M, van de Beek D, Sahanic S, Tancevski I, Stepanovskyy Y, Boyarchuk O, Nukui Y, Tsumura M, Vidaur L, Tangye SG, Burrel S, Duffy D, Quintana-Murci L, Klocperk A, Kann NY, Shcherbina A, Lau YL, Leung D, Coulongeat M, Marlet J, Koning R, Reyes LF, Chauvineau-Grenier A, Venet F, Monneret G, Nussenzweig MC, Arrestier R, Boudhabhay I, Baris-Feldman H, Hagin D, Wauters J, Meyts I, Dyer AH, Kennelly SP, Bourke NM, Halwani R, Sharif-Askari NS, Dorgham K, Sallette J, Sedkaoui SM, AlKhater S, Rigo-Bonnin R, Morandeira F, Roussel L, Vinh DC, Ostrowski SR, Condino-Neto A, Prando C, Bonradenko A, Spaan AN, Gilardin L, Fellay J, Lyonnet S, Bilguvar K, Lifton RP, Mane S, Anderson MS, Boisson B, Béziat V, Zhang SY, Vandreakos E, Hermine O, Pujol A, Peterson P, Mogensen TH, Rowen L, Mond J, Debette S, de Lamballerie X, Duval X, Mentré F, Zins M, Soler-Palacin P, Colobran R, Gorochov G, Solanich X, Susen S, Martinez-Picado J, Raoult D, Vasse M, Gregersen PK, Piemonti L, Rodríguez-Gallego C, Notarangelo LD, Su HC, Kisand K, Okada S, Puel A, Jouanguy E, Rice CM, Tiberghien P, Zhang Q, Cobat A, Abel L, and Casanova JL
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Neutralizing blood, Antibodies, Neutralizing immunology, Autoantibodies blood, COVID-19 mortality, Case-Control Studies, Child, Child, Preschool, Critical Illness, Humans, Immunoglobulin G blood, Immunoglobulin G immunology, Infant, Infant, Newborn, Interferon-alpha immunology, Middle Aged, Young Adult, Autoantibodies immunology, COVID-19 immunology, Interferon Type I immunology
- Abstract
Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases., (Copyright © 2021, American Association for the Advancement of Science.)
- Published
- 2021
- Full Text
- View/download PDF
42. [Genetic predisposition to mucocutaneous fungal infections].
- Author
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Baghad B, Bousfiha AA, Chiheb S, and Ailal F
- Subjects
- Genetic Predisposition to Disease, Humans, Candidiasis, Chronic Mucocutaneous epidemiology, Candidiasis, Chronic Mucocutaneous genetics, Immunologic Deficiency Syndromes, Mycoses
- Abstract
Mucocutaneous fungal infections are common and usually occur in the presence of certain risk factors. However, these infections can occur in patients with no known risk factors. This indicates the presence of an underlying genetic susceptibility to fungi reflecting an innate or adaptive immune deficiency. In this review, we highlight genetic factors that predispose to mucocutaneous fungal infections specially candidiasis and dermatophytosis., (Copyright © 2021 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
43. Correction to: The Seven STAT3‑Related Hyper‑IgE Syndromes.
- Author
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Fadil I, Ben-Ali M, Jeddane L, Barbouche MR, and Bousfiha AA
- Published
- 2021
- Full Text
- View/download PDF
44. The Seven STAT3-Related Hyper-IgE Syndromes.
- Author
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Fadil I, Ben-Ali M, Jeddane L, Barbouche MR, and Bousfiha AA
- Subjects
- Humans, Signal Transduction genetics, Immunoglobulin E genetics, Job Syndrome genetics, Mutation genetics
- Published
- 2021
- Full Text
- View/download PDF
45. [Pediatric sepsis: towards a rapid transfer to the Pediatric Intensive Care Unit (PICU)].
- Author
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Aissaoui O, El-Bouz M, Bousfiha AA, Gueddari W, and Chlilek A
- Subjects
- Child, Humans, Infant, Retrospective Studies, Intensive Care Units, Pediatric, Sepsis diagnosis, Sepsis therapy
- Abstract
Competing Interests: Les auteurs ne déclarent aucun conflit d´intérêts.
- Published
- 2021
- Full Text
- View/download PDF
46. Omenn syndrome caused by a novel homozygous mutation in recombination activating gene 1.
- Author
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Benhsaien I, Essadssi S, Elkhattabi L, Bakhchane A, Abdelghaffar H, Bousfiha AA, Badou A, and Barakat A
- Subjects
- Alleles, Amino Acid Substitution, Female, Genetic Association Studies, Humans, Infant, Phenotype, Sequence Analysis, DNA, Genes, RAG-1, Genetic Predisposition to Disease, Homozygote, Mutation, Severe Combined Immunodeficiency diagnosis, Severe Combined Immunodeficiency genetics
- Abstract
Omenn syndrome (OS) is a type of severe combined immunodeficiency (SCID) that is distinguished by, lymphadenopathy, hepatosplenomegaly, erythroderma, alopecia with normal to elevated T-cell counts, eosinophilia, and elevated serum IgE levels. Recombination activation gene (RAG) 1 or RAG2 mutations that result in partial V(D)J recombination activity are known to be the main cause of OS. Other genes (DCLRE1C, LIG4, IL7RA, common gamma chain, ADA, RMRP, and CHD7) have also been linked to OS, although with low frequency. Here, we report a two-month-old Moroccan girl from consanguineous marriage with chronic diarrhea, recurrent and opportunistic infections, failure to thrive, desquamative erythroderma, hepatosplenomegaly, and axillary lymphadenitis. The immunological assessment showed normal lymphocyte and NK cell counts but an absence of B cells, agammaglobulinemia contrasting with a high level of IgE. On the other hand, Sanger sequencing of RAG1 and RAG2 exon 2 regions revealed a new homozygous deleterious mutation in the RAG1 gene. This c.1184C > T mutation caused a change from Proline to Leucine at position 395 of the protein, leading to a partial loss of function. Early and rapid diagnosis of the disease may facilitate urgent life-saving treatment., (Copyright © 2021 Elsevier GmbH. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
47. Clinical and Immunological Features of 96 Moroccan Children with SCID Phenotype: Two Decades' Experience.
- Author
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Benhsaien I, Ailal F, El Bakkouri J, Jeddane L, Ouair H, Admou B, Bouskraoui M, Hbibi M, Hida M, Amenzoui N, Jouhadi Z, El Hafidi N, Rada N, Benajiba N, Abilkassem R, Badou A, and Bousfiha AA
- Subjects
- Alleles, Biomarkers, Consanguinity, Cross-Sectional Studies, Diagnosis, Differential, Disease Management, Disease Susceptibility, Genetic Predisposition to Disease, Genotype, Humans, Inheritance Patterns, Morocco epidemiology, Public Health Surveillance, Severe Combined Immunodeficiency etiology, Phenotype, Severe Combined Immunodeficiency diagnosis, Severe Combined Immunodeficiency epidemiology
- Abstract
Severe combined immunodeficiency (SCID) is a heterogeneous group of primary immunodeficiency diseases (PIDs) characterized by a lack of autologous T lymphocytes. This severe PID is rare, but has a higher prevalence in populations with high rates of consanguinity. The epidemiological, clinical, and immunological features of SCIDs in Moroccan patients have never been reported. The aim of this study was to provide a clinical and immunological description of SCID in Morocco and to assess changes in the care of SCID patients over time. This cross-sectional retrospective study included 96 Moroccan patients referred to the national PID reference center at Casablanca Children's Hospital for SCID over two decades, from 1998 to 2019. The case definition for this study was age < 2 years, with a clinical phenotype suggestive of SCID, and lymphopenia, with very low numbers of autologous T cells, according to the IUIS Inborn Errors of Immunity classification. Our sample included 50 male patients, and 66% of the patients were born to consanguineous parents. The median age at onset and diagnosis were 3.3 and 6.5 months, respectively. The clinical manifestations commonly observed in these patients were recurrent respiratory tract infection (82%), chronic diarrhea (69%), oral candidiasis (61%), and failure to thrive (65%). The distribution of SCID phenotypes was as follows: T-B-NK+ in 44.5%, T-B-NK- in 32%, T-B+NK- in 18.5%, and T-B+NK+ in 5%. An Omenn syndrome phenotype was observed in 15 patients. SCID was fatal in 84% in the patients in our cohort, due to the difficulties involved in obtaining urgent access to hematopoietic stem cell transplantation, which, nevertheless, saved 16% of the patients. The autosomal recessive forms of the clinical and immunological phenotypes of SCID, including the T-B-NK+ phenotype in particular, were more frequent than those in Western countries. A marked improvement in the early detection of SCID cases over the last decade was noted. Despite recent progress in SCID diagnosis, additional efforts are required, for genetic confirmation and particularly for HSCT.
- Published
- 2021
- Full Text
- View/download PDF
48. Pediatric Demodicosis Associated with Gain-of-Function Variant in STAT1 Presenting as Rosacea-Type Rash.
- Author
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Baghad B, El Fatoiki FZ, Benhsaien I, Bousfiha AA, Puel A, Migaud M, Chiheb S, and Ailal F
- Subjects
- Alleles, Child, DNA Mutational Analysis, Exanthema diagnosis, Exanthema etiology, Female, Humans, Metronidazole therapeutic use, Rosacea drug therapy, Skin pathology, Treatment Outcome, Gain of Function Mutation, Genetic Association Studies methods, Genetic Predisposition to Disease, Phenotype, Rosacea diagnosis, Rosacea etiology, STAT1 Transcription Factor genetics
- Published
- 2021
- Full Text
- View/download PDF
49. Severe Combined Immunodeficiency Disorder due to a Novel Mutation in Recombination Activation Gene 2: About 2 Cases.
- Author
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Benhsaien I, Ailal F, Elazhary K, El Bakkouri J, Badou A, and Bousfiha AA
- Abstract
Severe combined immunodeficiency (SCID) comprises a heterogeneous group of inherited immunologic disorders with profound defects in cellular and humoral immunity. SCID is the most severe PID and constitutes a pediatric emergency. Affected children are highly susceptible to bacterial, viral, fungal, and opportunistic infections with life-threatening in the absence of hematopoietic stem cell transplantation. We report here two cases of SCID. The first case is a girl diagnosed with SCID at birth based on her family history and lymphocyte subpopulation typing. The second case is a 4-month-old boy with a history of recurrent opportunistic infections, BCGitis, and failure to thrive, and the immunology workup confirms a SCID phenotype. The genetic study in the two cases revealed a novel mutation in the RAG2 gene, c.826G > A (p.Gly276Ser), in a homozygous state. The novel mutation in the RAG2 gene identified in our study may help the early diagnosis of SCID., Competing Interests: The authors declare that they have no commercial relationship or potential conflicts of interest related to the submission., (Copyright © 2021 Ibtihal Benhsaien et al.)
- Published
- 2021
- Full Text
- View/download PDF
50. Learning difficulties of medicine. Perceptions and expectations of medical students in Morocco.
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Abd Abou Sahda AH, Bourgadi JE, Bousfiha AA, and Ben Abdelaziz A
- Subjects
- Cognition, Female, Humans, Male, Morocco, Motivation, Schools, Medical, Students, Medical psychology
- Abstract
Context: Morocco, like other countries of the Great Maghreb, does not use their mother language (Arabic) nor the dominant one (English), in teaching medicine, which could create cognitive barriers in assimilating knowledge and developing innovations., Objective: To explore attitudes of a representative sample of students from Moroccan medical faculties, towards their current learning difficulties and their expectations, vis-à-vis their linguistic reform projects at the Moroccan University., Methods: This descriptive study included a proportional stratified sample of students (both sexes) from the Faculties of Medicine and Pharmacy of Moroccan universities, during the 2019-2020 academic year. It used an exploratory questionnaire of language skills, academic assimilation, and suggestions for language alternatives., Results: A sample of 891 Moroccan medical students, responding to the questionnaire (sex ratio of 0.68), from the eight faculties of medicine, were from two secondary education streams: Arabic and French. The students declared their good level in "reading and comprehension" and "speaking" in Arabic, respectively by 63% and 39% of the respondents, and in using the French language respectively by 44% and 26%. Third of the respondents admitted that the French language negatively affected their academic success, by increasing the time required for learning (44%) and by weakening their ability to communicate with patients (21%). More than half of the students were aware of the dialectic relationship between the language used, and assimilation, identity, scientific creativity, and economics. The future options of the linguistic problems of medical training in Morocco were mainly distributed, according to the respondents, either on using the English language (69%) or on partial (42%), total (37%) arabization of medical courses., Conclusion: Despite linguistic mastery of medical students, in Morocco, they recognized their learning difficulties in French and expressed their conviction to linguistic review, based currently on a triad of languages (including the mother language). While waiting for linguistic standardization in medical schools, bilingualism (mother language and English language) was the option suggested by the majority of Moroccan students.
- Published
- 2021
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