Ouederni M.,Pediatric Hematology Immunology Unit |
Vincent Q.B.,University of Paris Descartes |
Vincent Q.B.,French Institute of Health and Medical Research |
Frange P.,Pediatric Hematology Immunology Unit |
And 23 more authors.
Blood | Year: 2011
Inherited deficiency of major histocompatibility complex (MHC) class II molecules impairs antigen presentation to CD4 +T cells and results in combined immunodeficiency (CID). Autosomal-recessive mutations in the RFXANK gene account for two-thirds of all cases of MHC class II deficiency. We describe here the genetic, clinical, and immunologic features of 35 patients from 30 unrelated kindreds from North Africa sharing the same RFXANK founder mutation, a 26-bp deletion called I5E6-25-I5E6 + 1), and date the founder event responsible for this mutation in this population to approximately 2250 years ago (95% confidence interval [CI]: 1750-3025 years). Ten of the 23 patients who underwent hematopoietic stem cell transplantation (HSCT) were cured, with the recovery of almost normal immune functions. Five of the patients from this cohort who did not undergo HSCT had a poor prognosis and eventually died (at ages of 1-17 years). However, 7 patients who did not undergo HSCT (at ages of 6-32 years) are still alive on Ig treatment and antibiotic prophylaxis. RFXANK deficiency is a severe, often fatal CID for which HSCT is the only curative treatment. However, some patients may survive for relatively long periods if multiple prophylactic measures are implemented. © 2011 by The American Society of Hematology. Source
Talmoudi F.,Institute Pasteur Of Tunis |
Kilani O.,Institute Pasteur Of Tunis |
Ayed W.,Institute Pasteur Of Tunis |
Ben Halim N.,Institute Pasteur Of Tunis |
And 16 more authors.
Comptes Rendus - Biologies | Year: 2013
Fanconi anemia (FA) is a recessive chromosomal instability syndrome that is clinically characterized by multiple symptoms. Chromosome breakage hypersensitivity to alkylating agents is the gold standard test for FA diagnosis. In this study, we provide a detailed laboratory protocol for accurate assessment of FA diagnosis based on mitomycin C (MMC) test. Induced chromosomal breakage study was successful in 171 out of 205 aplastic anemia (AA) patients. According to the sensitivity of MMC at 50 ng/ml, 38 patients (22.22%) were diagnosed as affected and 132 patients (77.17%) as unaffected. Somatic mosaicism was suspected in an 11-year-old patient with a FA phenotype. Twenty-six siblings of FA patients were also evaluated and five of them (19.23%) were diagnosed as FA. From this study, a standard protocol for diagnosis of FA was developed. It is routinely used as a diagnostic test of FA in Tunisia.© 2012 Académie des sciences. Source
Aadam Z.,Hassan II University |
Aadam Z.,Institute Pasteur |
Kechout N.,Institute Pasteur dAlgerie |
Barakat A.,Institute Pasteur |
And 29 more authors.
Journal of Clinical Immunology | Year: 2016
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. © 2016, Springer Science+Business Media New York. Source
Ben Nasr M.,National Blood Transfusion Center |
Reguaya Z.,National Blood Transfusion Center |
Berraies L.,National Blood Transfusion Center |
Maamar M.,Apheris Unit |
And 6 more authors.
Transplantation Proceedings | Year: 2011
We explored the influence of polymorphisms in genes encoding the chemokine stromal cellderived factor-1 (SDF-1)/CXCL12 in a cohort of Tunisian patients with malignant hematologic diseases multiple myeloma [MM], non-Hodgkin's lymphoma [NHL], Hodgkin's disease, and acute myeloid leukemia [AML], who underwent stem cell mobilization for autologous transplantation versus a group of healthy donors for allogeneic transplantation. Polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLp) analysis was used for rapid identification of genotypes. Significant associations for SDF1-3′A polymorphism were observed exclusively in patients with MM and NHL. While there was a lack of all association of SDF-1 polymorphism with AML patients. However, considering that the ability of mobilization varies among subjects, we have observed that the SDF1-3′A allele was associated with good mobilization capacity. Interestingly, the association was mainly observed among healthy allogeneic transplant donors where the analysis was not biased by background disease or chemotherapy (P = .010; odds ratio = 2.603; confidence interval [95%] = 1.2395.466). Source
Raddaoui A.,Laboratory of the National Bone Marrow Transplantation Center |
Raddaoui A.,University of Carthage |
Simoes A.S.,New University of Lisbon |
Baaboura R.,Laboratory of the National Bone Marrow Transplantation Center |
And 9 more authors.
PLoS ONE | Year: 2015
Background Pneumococcal disease, a major cause of morbidity and mortality globally, has higher incidence among young children, the elderly and the immunocompromised of all ages. In Tunisia, pneumococcal conjugate vaccines (PCVs) are not included in the national immunization program. Also, few studies have described the epidemiology of S. pneumoniae in this country and, in particular, no molecular typing studies have been performed. The aim of this study was to evaluate serotype distribution, antimicrobial resistance and clonality of Streptococcus pneumoniae isolated from neutropenic patients in Tunisia. Methods Fifty-nine S. pneumoniae were isolated from infection (n = 31) and colonization (n = 28) sites of patients (children and adults) attending the National Centre of Bone Marrow Transplantation in Tunis between 2005-2011. All isolates were characterized by serotype, antimicrobial resistance pattern and multilocus sequence typing (MLST). Results The majority (66.1%) of the isolates belonged to five serotypes all included in PCVs: 6B, 9V, 14, 19F and 23F. The potential coverage of the 10-valent and 13-valent PCV was of 71.2% and 76.3% respectively. Resistance rates were very high and 69.5% of the isolates were multidrug resistant: non-susceptibility rates to penicillin, amoxicillin and cefotaxime were 66.1%, 40.7%and 27.1%, respectively; resistance rates to erythromycin, clindamycin, tetracycline, chloramphenicol and trimethoprim-sulfamethoxazole, were 69.5%, 61.0%, 37.3%, 22.0% and 67.8%, respectively. The most frequent serotypes had STs characteristic of multidrug resistant international clones known to be highly successful and important causes of pneumococcal infection: Spain 23F-ST81, France 9V/14-ST156, Spain 6B-ST90, 19FST320, and Portugal 19F-ST177. Conclusions The majority of S. pneumoniae strains recovered from immunocompromised patients in Tunisia are representatives of multidrug resistant pandemic clones that express serotypes targeted by PCVs. To contain the burden of pneumococcal disease and improve treatment choices among Tunisian immunocompromised patients PCVs should be offered to all of them. © 2015 Raddaoui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source