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1.
J Clin Immunol ; 43(2): 485-494, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36367635

RESUMO

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.


Assuntos
Testes Genéticos , Humanos , Estudos Retrospectivos , Mutação/genética , Doenças da Deficiência Hereditária de Complemento , Marrocos/epidemiologia
2.
J Clin Immunol ; 41(3): 631-638, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33411152

RESUMO

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.


Assuntos
Fenótipo , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/epidemiologia , Alelos , Biomarcadores , Consanguinidade , Estudos Transversais , Diagnóstico Diferencial , Gerenciamento Clínico , Suscetibilidade a Doenças , Predisposição Genética para Doença , Genótipo , Humanos , Padrões de Herança , Marrocos/epidemiologia , Vigilância em Saúde Pública , Imunodeficiência Combinada Severa/etiologia
3.
Tunis Med ; 102(1): 1-6, 2024 Jan 05.
Artigo em Francês | MEDLINE | ID: mdl-38545722

RESUMO

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.


Assuntos
Anemia Hemolítica Autoimune , Citopenia , Púrpura Trombocitopênica Idiopática , Trombocitopenia , Criança , Humanos , Púrpura Trombocitopênica Idiopática/terapia , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Anemia Hemolítica Autoimune/terapia , Anemia Hemolítica Autoimune/tratamento farmacológico , Trombocitopenia/diagnóstico , Trombocitopenia/terapia
4.
Viruses ; 16(9)2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39339890

RESUMO

Epidermodysplasia verruciformis (EV) is a rare genodermatosis caused by ß-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.


Assuntos
Epidermodisplasia Verruciforme , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas Serina-Treonina Quinases , Humanos , Epidermodisplasia Verruciforme/genética , Epidermodisplasia Verruciforme/virologia , Epidermodisplasia Verruciforme/patologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/deficiência , Masculino , Feminino , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Linhagem , Marrocos , Sequenciamento do Exoma , Criança , Pré-Escolar , Mutação
6.
Pan Afr Med J ; 26: 212, 2017.
Artigo em Francês | MEDLINE | ID: mdl-28690727

RESUMO

Hyper IgM syndrome is a well known genetic (primary) immunodeficiency disorder which was first described in 1961. It is caused by B lymphocyte deficiency characterized by normal or elevated serum IgM levels and low or zero levels of IgG, IgA, IgE resulting from isotype-switching deficiency. Clinical manifestations are dominated by recurrent infections, especially involving the digestive tube of the ENT sphere and the lungs. This syndrome is caused by B-cell immunoglobulin class switch deficiency and decreased capacity to induce proliferation of T lymphocytes. The net result of these deficiencies is reflected in increased susceptibility to Pneumocystis jiroveci, Cryptosporidium spp and other intracellular organisms as well as high rate of bacterial and viral infections. This study aimed to illustrate the importance of understanding the pathophysiological mechanisms associated with this increased susceptibility to infections in order to allow a better diagnosis and therapy in patients with Hyper IgM syndrome (HIM).


Assuntos
Linfócitos B/imunologia , Síndrome de Imunodeficiência com Hiper-IgM/fisiopatologia , Infecções Oportunistas/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Síndrome de Imunodeficiência com Hiper-IgM/imunologia , Imunoglobulina M/sangue , Lactente , Masculino , Marrocos , Infecções Oportunistas/epidemiologia , Infecções Oportunistas/microbiologia , Linfócitos T/imunologia
7.
Infect Dis (Lond) ; 47(1): 27-32, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25329550

RESUMO

BACKGROUND: The importance of community-acquired infections due to extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) has been increasingly recognized in recent years. This study aimed to determine the prevalence of intestinal carriage of ESBL-PE in the community in Casablanca, Morocco. METHODS: During 6 months (2013), 93 fecal samples were examined for ESBL-PE. Isolates expressing an ESBL phenotype were investigated for the presence of genes encoding ß-lactamases and plasmid-mediated quinolone resistance. Conjugation experiments were done to determine the mobility of ESBL genes. RESULTS: The prevalence of fecal carriage of ESBL-PE was 4.3% (4/93; 95% CI, 0.2-8.4). Klebsiella pneumoniae (n = 2), Enterobacter cloacae (n = 2), Escherichia coli (n = 1), and Serratia odorifera (n = 1) were the ESBL-producing species. Four (66.7%) of these isolates were multidrug-resistant. The blaSHV-12 (n = 5) was the most frequent ESBL gene detected, followed by blaCTX-M-15 (n = 3).The non-ESBL gene detected was blaTEM-1 (n = 5). One isolate harbored the qnrB1 variant. RESULTS of conjugation experiments indicated that blaSHV-12 + blaTEM-1 + qnrB1 and blaCTX-M-15 + blaTEM-1 genes were co-transferred and that these genes were carried by a conjugative plasmid of high molecular weight (125 kb). CONCLUSION: Our results show the importance of the intestinal tract as a reservoir for ESBL-PE in the community in Morocco.


Assuntos
Portador Sadio/epidemiologia , Infecções por Enterobacteriaceae/epidemiologia , Fezes/microbiologia , Adulto , Idoso , Antibacterianos/farmacologia , Ciprofloxacina/farmacologia , Enterobacter cloacae/efeitos dos fármacos , Enterobacter cloacae/enzimologia , Enterobacter cloacae/genética , Feminino , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/genética , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Marrocos , Norfloxacino/farmacologia , Serratia/efeitos dos fármacos , Serratia/enzimologia , Serratia/genética , Adulto Jovem , Resistência beta-Lactâmica , beta-Lactamases/genética
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