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INTRODUCTION: Inborn errors of immunity (IEI) represent a heterogeneous large group of genetic disorders characterized by susceptibility of affected individuals to recurrent infections, autoimmune/inflammatory diseases, allergy, and malignancy. We aimed to report for the first time the Algerian registry for IEI in children. METHODS: We described the characteristics of IEI in Algerian children from the data collected in the Algerian registry for IEI between 1985 and 2021. RESULTS: Over a period of 37 years, we included 887 children (530 male, 59.6%) with a mean age at diagnosis of 3.23 years and a mean diagnosis delay of 2 years. The prevalence rate was estimated at 1.97/100,000 inhabitants or 5.91/100,000 children. The parental consanguinity was found in 52.6%. The most prevalent category was combined immunodeficiencies (CID) (35.5%), followed by predominantly antibody deficiencies (24.5%) and CID with syndromic features (18.3%). The most predominant diseases were severe CID (134 cases), MHC II deficiency (99 cases), agammaglobulinemia (82 cases), common variable immunodeficiency (78 cases), hyper IgE syndromes (61 patients), ataxia-telangiectasia (46 patients), Wiskott-Aldrich syndrome (40 patients) and chronic granulomatous disease (39 cases). The clinical presentation was dominated by lower respiratory tract infections (69%), failure to thrive (38.3%), and chronic diarrhea (35.2%). Genetic analysis was performed in 156 patients (17.6%). The global mortality rate was 28.4% mainly caused by CID. CONCLUSION: This is the first report of the Algerian registry for IEI in children. Data is globally similar to that of the Middle East and North African (MENA) registries with high consanguinity, predominance of CID, and significant mortality. This registry highlights the weak points that should be improved in order to provide better patient care.
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Agammaglobulinemia , Síndromes de Inmunodeficiencia , Enfermedades de Inmunodeficiencia Primaria , Niño , Humanos , Masculino , Argelia/epidemiología , Síndromes de Inmunodeficiencia/diagnóstico , Síndromes de Inmunodeficiencia/epidemiología , Síndromes de Inmunodeficiencia/genética , Agammaglobulinemia/epidemiología , Sistema de RegistrosRESUMEN
BACKGROUND: Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis. METHODS: We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers. RESULTS: We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity was present in 60.5% of cases and 27.3% of the patients were from families with a confirmed previous family history of IEI. The median age of patients at the onset of disease was 36 months and the median delay in diagnosis was 41 months. The rate of registered IEI patients ranges between 0.02 and 7.58 per 100,000 population, and the lowest rates were in countries with the highest rates of disability-adjusted life years (DALY) and death rates for children. Predominantly antibody deficiencies were the most frequent IEI entities diagnosed in 41.2% of the cohort. Among 5871 patients genetically evaluated, the diagnostic yield was 83% with the majority (65.2%) having autosomal recessive defects. The mortality rate was the highest in patients with non-syndromic combined immunodeficiency (51.7%, median age: 3.5 years) and particularly in patients with mutations in specific genes associated with this phenotype (RFXANK, RAG1, and IL2RG). CONCLUSIONS: This comprehensive registry highlights the importance of a detailed investigation of IEI patients in the MENA region. The high yield of genetic diagnosis of IEI in this region has important implications for prevention, prognosis, treatment, and resource allocation.
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Enfermedades Genéticas Congénitas/epidemiología , Enfermedades de Inmunodeficiencia Primaria/epidemiología , Adolescente , Adulto , África del Norte/epidemiología , Anciano , Niño , Consenso , Años de Vida Ajustados por Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medio Oriente/epidemiología , Sistema de Registros , Adulto JovenRESUMEN
Macrozoospermia is associated with severe male infertility. To date, the only gene implicated in this phenotype is the Aurora Kinase C gene. We report in this work the genetic screening of AURKC mutations in 34 patients with macrozoospermia among 3,536 Algerian infertile men. Nineteen patients (56%) were homozygotes for the c.144delC mutation, eight (23.52%) homozygotes for the c.744C>G (p.Y248*) mutation and two (5.88%) compound heterozygotes. No AURKC mutation was identified in five patients (14.7%). Interestingly and although it is generally accepted that nearly all positive mutated AURKC patients have close to 100% large-head spermatozoa, our results showed that 11 patients with AURKC mutations (32.35%) had large-headed spermatozoa lower than 70% (7 with c.144delC and 4 with p.Y248*), and no mutation was found in 2 patients who had >70% of macrocephalic spermatozoa. Twenty ICSI attempts were performed before genetic screening resulting in 39 embryos but no pregnancy was obtained. The sequencing of AURKC exons 3 and 6 is appropriate as a first-line genetic exploration in these patients to avoid unsuccessful ICSI attempts. A percentage of large head spermatozoa beyond 25% and a percentage of multiflagellar spermatozoa beyond 10% are predictive of a positive mutation diagnosis.
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Infertilidad Masculina , Aurora Quinasa C/genética , Homocigoto , Humanos , Infertilidad Masculina/genética , Masculino , Mutación , EspermatozoidesRESUMEN
The aim of this study was to assess the oxidative stress and the genotoxicity induced by chemotherapy by the determination of plasma malondialdehyde (MDA) level, protein carbonyl (PC) content, superoxide dismutase (SOD) activity and lymphocyte DNA damage in Algerian children with lymphoma. The study population included thirty patients with lymphoma and fifty healthy controls. Patients were treated with 2 courses of OEPA (oncovin 1,5 mg/m2, etoposide 125 mg/m2, prednisone 60 mg/m2 and doxorubicin 40 mg/m2) followed by 2 to 4 courses of COPDAC (cyclophosphamide 500 mg/m2, oncovin 1,5 mg/m2, dacarbazine 250 mg/m2 and prednisone 40 mg/m2). Plasma levels of MDA, PC and SOD were spectrophotometrically measured. DNA damage was assessed by alkaline comet assay in peripheral blood leukocytes. Plasma MDA, PC levels and lymphocyte DNA damage, were found to be significantly higher in lymphoma patients than in controls (p < 0.001). Whereas, SOD activity in lymphoma patients was significantly lower than in healthy controls (p < 0.001). There were significant positive correlations between DNA damage, MDA and PC in patients (r = 0.96, p < 0.001, r = 0.97, p < 0.001, respectively), and negative correlation with SOD (r = -0.87, p < 0.01). Our results indicated that, leukocytes DNA damage and oxidative stress were significantly higher in lymphoma patients, suggesting that the direct effect of chemotherapy and the alteration of the redox balance may influence oxidative/antioxidative status.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Daño del ADN/efectos de los fármacos , Linfoma/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Adolescente , Argelia , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Antioxidantes/metabolismo , Estudios de Casos y Controles , Niño , Preescolar , Ensayo Cometa , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/farmacología , Etopósido/administración & dosificación , Etopósido/efectos adversos , Etopósido/farmacología , Femenino , Humanos , Linfocitos/efectos de los fármacos , Linfocitos/patología , Masculino , Malondialdehído/metabolismo , Oxidación-Reducción/efectos de los fármacos , Prednisona/administración & dosificación , Prednisona/efectos adversos , Prednisona/farmacología , Vincristina/administración & dosificación , Vincristina/efectos adversos , Vincristina/farmacologíaRESUMEN
PURPOSE: X-linked agammagobulinemia (XLA) is a primary immunodeficiency caused by Bruton's tyrosine kinase (BTK) gene defect. XLA patients have absent or reduced number of peripheral B cells and a profound deficiency in all immunoglobulin isotypes. This multicenter study reports the clinical, immunological and molecular features of Bruton's disease in 40 North African male patients. METHODS: Fifty male out of 63 (male and female) patients diagnosed with serum agammaglobulinemia and non detectable to less than 2% peripheral B cells were enrolled. The search for BTK gene mutations was performed for all of them by genomic DNA amplification and Sanger sequencing. RESULTS: We identified 33 different mutations in the BTK gene in 40 patients including 12 missense mutations, 6 nonsense mutations, 6 splice-site mutations, 5 frameshift, 2 large deletions, one complex mutation and one in-frame deletion. Seventeen of these mutations are novel. This large series shows a lower frequency of XLA among male patients from North Africa with agammaglobulinemia and absent to low B cells compared with other international studies (63.5% vs. 85%). No strong evidence for genotype-phenotype correlation was observed. CONCLUSIONS: This study adds to other reports from highly consanguineous North African populations, showing lower frequency of X-linked forms as compared to AR forms of the same primary immunodeficiency. Furthermore, a large number of novel BTK mutations were identified and could further help identify carriers for genetic counseling.
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Agammaglobulinemia/genética , Expresión Génica , Frecuencia de los Genes , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Mutación , Infecciones Oportunistas/genética , Proteínas Tirosina Quinasas/genética , Adulto , Agammaglobulinemia Tirosina Quinasa , Agammaglobulinemia/complicaciones , Agammaglobulinemia/diagnóstico , Agammaglobulinemia/inmunología , Edad de Inicio , Argelia , Alelos , Linfocitos B/inmunología , Linfocitos B/patología , Niño , Preescolar , Estudios de Asociación Genética , Asesoramiento Genético , Enfermedades Genéticas Ligadas al Cromosoma X/complicaciones , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/inmunología , Heterocigoto , Humanos , Lactante , Masculino , Marruecos , Infecciones Oportunistas/complicaciones , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/inmunología , Proteínas Tirosina Quinasas/inmunología , Análisis de Secuencia de ADN , TúnezRESUMEN
BACKGROUND: Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) are the 2 types of lymphoma that represent the third most common childhood malignancy. Multiple etiological factors are involved in lymphoma pathogenesis, including viral infection, immune deficiencies, environmental agents, and genetic factors. Strong arguments supporting a genetic linkage between the susceptibility to lymphomas and human leukocyte antigens (HLA) are reported and give an idea about susceptibility or protection from the disease. METHODS: Seventy-one cases were included in this study: 36 cases of non-Hodgkin lymphoma and 35 patients with Hodgkin lymphoma. Their ages ranged from 4 to 18 years. The control group consisted of 70 unrelated healthy individuals, with a mean age of 5 to 17 years. The genotype of HLA-A, HLA-B, HLA-DR, and HLA-DQ alleles was typed by means of PCR sequence-specific priming. RESULTS: HLA-B*18, HLA-DRB1*03, *07, and HLA-DQB1*02 were significantly increased in patients with lymphomas when compared with controls, whereas HLA-DRB1*13 and DQB1*03 were significantly decreased when compared with controls. CONCLUSIONS: These results indicate that HLA-B*18, DRB1*03, *07, and DQB1*02 may contribute to lymphoma susceptibility, whereas HLA-DRB1*13 and DQB1*03 may confer protection to lymphoma in the Algerian population.
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Genes MHC Clase II , Genes MHC Clase I , Antígenos HLA/genética , Enfermedad de Hodgkin/genética , Linfoma no Hodgkin/genética , Polimorfismo Genético , Argelia/epidemiología , Alelos , Niño , Preescolar , Etnicidad/genética , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Enfermedad de Hodgkin/epidemiología , Enfermedad de Hodgkin/etnología , Humanos , Linfoma no Hodgkin/epidemiología , Linfoma no Hodgkin/etnología , MasculinoRESUMEN
Scorpion envenoming (SE) is a public health problem in developing countries. In Algeria, the population exposed to the risk of SE was estimated at 86.45% in 2019. Thus, the development of a vaccine to protect the exposed population against scorpion toxins would be a major advance in the fight against this disease. This work aimed to evaluate the immunoprotective effect of a Multiple Antigenic Peptide against the Aah II toxin of Androctonus australis hector scorpion, the most dangerous scorpion species in Algeria. The immunogen MAP1Aah2 was designed and tested accordingly. This molecule contains a B epitope, derived from Aah II toxin, linked by a spacer to a universal T epitope, derived from the tetanus toxin. The results showed that MAP1Aah2 was non-toxic despite the fact that its sequence was derived from Aah II toxin. The immunoenzymatic assay revealed that the 3 immunization regimens tested generated specific anti-MAP1Aah2 antibodies and cross-reacted with the toxin. Mice immunized with this immunogen were partially protected against mortality caused by challenge doses of 2 and 3 LD50 of the toxin. The survival rate and developed symptoms varied depending on the adjuvant and the challenge dose used. In the in vitro neutralization test, the immune sera of mice having received the immunogen with incomplete Freund's adjuvant neutralized a challenge dose of 2 LD50. Hence, the concept of using peptide dendrimers, based on linear epitopes of scorpion toxins, as immunogens against the parent toxin was established. However, the protective properties of the tested immunogen require further optimizations.
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BACKGROUND: Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder. It is characterized by a gradual decrease in cognitive function and is considered a disorder in which the intensifying neuronal loss. The autopsy is considered the gold standard for the diagnosis of AD and non-AD dementia. OBJECTIVE: Our study aims to clarify the involvement of neuroinflammation processes in brain lesions of AD. METHODS: The defunct was admitted to the forensic medicine department of Issad Hassani Hospital (Algeria). In order to recover the brain, an autopsy was performed within 24 hours of death and then immediately fixed in formaldehyde to maintain structural brain integrity for histological and immunohistochemical analysis. RESULTS: Our findings indicate the presence of tissue lesions in the specific brain regions: right middle frontal gyrus, right cingulate gyrus, right putamen and globus pallidus, right caudate nucleus, right hippocampus, inferior parietal lobule, left parahippocampal gyrus, and left hippocampus. Notably, there is a predominant occurrence of lesions: granulovacuolar degeneration, Hirano bodies, cotton-wool, and neuritic plaques. The causes of neurodegenerative processes are probably related to TNF-α, IL-1ß, and TGF-ß production and iNOS expression by the NF-κB activation pathway in the R-HP, inducing necroptosis. CONCLUSIONS: The occurrence of neuroinflammatory responses is linked to tissue lesions in AD. The production of inflammatory cytokines is the basis of this process, which ultimately leads to the necroptosis, which is triggered by neuroinflammation amplification. The inhibition of neuroinflammation by targeting TNF-α/iNOS could stop tissue damage, this may be a promising therapeutic pathway.
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Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/patología , Factor de Necrosis Tumoral alfa/metabolismo , Enfermedades Neuroinflamatorias , Encéfalo/patología , Inflamación/metabolismo , AutopsiaRESUMEN
ABSTRACT: Myasthenia gravis (MG) is an autoimmune disease of multifactorial etiology in which genetic factors and cytokines seem to play an important role. The aim of this study was to investigate potential associations of cytokines single nucleotide polymorphisms (SNPs) and MG in Algerian patients. We performed a case-control study that included 27 patients and 74 healthy subjects. Cytokines SNPs genotyping was performed by the polymerase chain reaction sequence-specific primers (PCR-SSP) method. Our results showed that the TNF-α -308G/A (P < 0.005) and TGF-ß1 +869T/T (P < 0.05) genotypes were more frequent among patients with MG compared with healthy individuals, whereas TNF-α -308G/G (P < 0.0001), TGF-ß1 +869T/C (P < 0.05), and IFN-γ +874A/A (P < 0.05) were less frequent. Our results also showed that IL-10 and IL-6 SNPs did not show any significant difference in distribution between MG patients and healthy individuals. Our observations support the hypothesis that implicates genetic variants of certain cytokines in MG. However, ours results should be replicated with a larger sample size. In addition, the precise underlying processes remain to be clarified. HIGHLIGHTS: TNF-α -308G/A and TGF-ß1 +869T/C genotypes predispose to MG.IFN-γ +874A/A genotype protects against MG.IL-6 -174C/G SNP is not associated with MG.
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Citocinas , Miastenia Gravis , Humanos , Citocinas/genética , Factor de Crecimiento Transformador beta1/genética , Polimorfismo de Nucleótido Simple/genética , Factor de Necrosis Tumoral alfa , Estudios de Casos y Controles , Interleucina-6 , Miastenia Gravis/genéticaAsunto(s)
Autoanticuerpos/inmunología , Calcinosis/inmunología , Dermatomiositis/inmunología , Corticoesteroides/uso terapéutico , Biopsia , Calcinosis/diagnóstico , Calcinosis/tratamiento farmacológico , Dermatomiositis/diagnóstico , Dermatomiositis/tratamiento farmacológico , Diagnóstico Diferencial , Electromiografía , Humanos , Masculino , Persona de Mediana Edad , SíndromeRESUMEN
BACKGROUND: Diabetic nephropathy is a common worldwide multifactorial disease where involvement of genetic factors is well etablished. The aim of this study was to investigate the HLA genes implication in the development of type 1 diabetic nephropathy. METHODS: We performed a case- control study where one hundred and fifty subjects were examined. Patients were divided in two groups; with and without type 1 diabetic nephropathy. HLA typing was performed using Polymerase Chain Reaction- Sequence Specific Oligonucleotide (PCR- SSO) method. HLA association to clinical phenotype and HLA haplotype analysis was also investigated. RESULTS: HLA B*51 is increased in patients without type 1 diabetic nephropathy (7.14% vs. 0 %, P <0.05, OR= 0), however no other studied alleles seem to have any effect (all P>0.05). Haplotype analysis also does not reveal any significant association, however, A*02-B*18-DRB1*03-DQA1*05- DQB1*03 haplotype shows a tendency to be associated with the development of diabetic nephropathy (P = 0.05). CONCLUSION: These results suggest a protective effect of HLA B*51 allele from type 1 diabetic nephropathy. However, further studies are required in order to clarify its potential implication as a protective marker.
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Diabetes Mellitus Tipo 1/genética , Nefropatías Diabéticas/genética , Antígenos HLA/genética , Adulto , Estudios de Casos y Controles , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/inmunología , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/inmunología , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Antígenos HLA/inmunología , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Factores Protectores , Medición de Riesgo , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: We aimed to assess Vitamin D levels in patients with Type 1 Diabetes (T1D) and to investigate the correlation between vitamin D and metabolic imbalance. MATERIAL AND METHODS: For our study, we selected thirty-one patients with T1D without complications and fifty-seven healthy controls. Diabetic patients were diagnosed using the criteria of the World Health Organization/American Diabetes Association. Vitamin D, Parathyroid Hormone (PTH), insulin and C peptide assay were performed using chimilunescence. Glucose level, lipid profile, glycated haemoglobin (HbA1c) and ionogram were also analysed. RESULTS: Vitamin D, HbA1c and Gly levels were found to be significant in T1D patients than in controls (P<0.5). However, for PTH, no significant difference was observed (P > 0. 05) and the results show a non-significant difference of total cholesterol potassium, sodium, phosphor and calcium concentration averages. CONCLUSION: Our results indicate that the deficiency of VD is associated with an increased risk of T1DM in Algerian population.
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Diabetes Mellitus Tipo 1/sangre , Metabolismo Energético , Deficiencia de Vitamina D/sangre , Vitamina D/sangre , Adulto , Argelia/epidemiología , Biomarcadores/sangre , Glucemia/análisis , Péptido C/sangre , Estudios de Casos y Controles , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiología , Femenino , Hemoglobina Glucada/análisis , Humanos , Insulina/sangre , Masculino , Hormona Paratiroidea/sangre , Factores de Riesgo , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/epidemiología , Adulto JovenRESUMEN
Major histocompatibility complex class I chain-related gene A (MICA-129) dimorphism was investigated in 73 autoimmune diabetes patients (type 1 diabetes and latent autoimmune diabetes in adults) and 75 controls from Algeria. Only MICA-129 Val allele and MICA-129 Val/Val genotype frequencies were higher among patients than in the control group. Statistical analysis of the estimated extended HLA-DR-DQ-MICA haplotypes shown that individual effects of MICA alleles on HLA-DQ2-DR3-MICA-129 Val/Val and HLA-DQ8-DR4-MICA-129 Val/Val haplotypes were significantly higher in patients than in the control groups. These preliminary data might suggest a relevant role of MICA-129 Val/Val single nucleotide polymorphism (weak/weak binders of NKG2D receptor) in the pathogenesis of T1D and LADA.