136 research outputs found
Primary Immunodeficiencies Worldwide
No full textThis eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contac
A Twenty year experience of Primary Immune Deficiencies’ investigations in resource-limited settings
No full textPrimary Immune Deficienes (PID) are a heterogeneous group of inherited disorders in
which immune system dysfunctions cause an enhanced susceptibility to infections that is
the common clinical feature of these diseases. To date, more than 200 genes have been
identified and associated with as many different immunodeficiencies. The frequency of
PIDs is higher in North-Africa and Middle-East as compared to Europe and North-
America. Indeed, our population is characterized by a high frequency of consanguineous
marriages which may reach 50% in rural areas. This may account for the higher
incidence of autosomal recessive immunodeficiencies observed.
During the last twenty years, we’ve diagnosed and investigated at the Institut Pasteur de
Tunis, a resource-limited institution, 655 tunisian cases of PIDs including patients with
combined immunodeficiencies, antibody deficiencies, phagocytosis defects, complement
deficiencies and other well-defined immunodeficiencies
Journal of Leukocyte Biology / Progress and history of the 10th Federation of African Immunological Societies Congress
No full textThe 10th Federation of African Immunological Societies (FAIS) Congress, held in Tunisia in November 2017, marked a significant scientific milestone. It enabled scientists from across the continent to promote immunology research and to showcase major achievements made by immunologists throughout Africa. This issue of the Journal of Leukocyte Biology (JLB) features manuscripts from the FAIS Congress. As noted in these papers, research in infectious diseases remains the focus of the African immunology community; however, increasingly noncommunicable diseasessuch as autoimmunity, allergy, primary immunodeficiency, cancer and transplantation immunologyare also an emerging priority. This overview gives a brief history of the FAIS meeting, which also commemorated the 25th anniversary of the FAIS. It describes the current activities of the organization, as well as its history and the future opportunities for this Federation.(VLID)510290
Novel insights into FAS defects underlying autoimmune lymphoproliferative syndrome revealed by studies in consanguineous patients.
No full textInternational audienceAutoimmune lymphoproliferative syndrome (ALPS) is a primary immunodeficiency disease due to impaired Fas-Fas ligand apoptotic pathway. It is characterized by chronic nonmalignant, noninfectious lymphadenopathy and/or splenomegaly associated with autoimmune manifestations primarily directed against blood cells. Herein, we review the heterogeneous ALPS molecular bases and discuss recent findings revealed by the study of consanguineous patients. Indeed, this peculiar genetic background favored the identification of a novel form of AR ALPS-FAS associated with normal or residual protein expression, expanding the spectrum of ALPS types. In addition, rare mutational mechanisms underlying the splicing defects of FAS exon 6 have been identified in AR ALPS-FAS with lack of protein expression. These findings will help decipher critical regions required for the tight regulation of FAS exon 6 splicing. We also discuss the genotype-phenotype correlation and disease severity in AR ALPS-FAS. Altogether, the study of ALPS molecular bases in endogamous populations helps to better classify the disease subgroups and to unravel the Fas pathway functioning
Omenn Syndrome : Two Case Reports
No full textOmenn syndrome is a variant of combined severe immunodeficiencydue to mutations in RAG genes. It is characterized by polymorph symptoms andlethal outcome. We report on two cases of Omenn syndrome. Infants were aged 50and 46 days. The clinical and biological signs were typical and complete in the firstcase. In the second case, only the cutaneous signs were present. Diagnosis was confirmedby genetic study. The Rag1 T631 mutation was found in these two patients.Hematopoietic stem cell transplantation could not be done and the evolution wasfatal in both cases because of severe infectious episodes. Prenatal diagnosis wasperformed in the two families and each family has currently a healthy child. In conclusion,early diagnosis of Omenn syndrome may avoid infectious complicationsresponsible for delay in therapeutic management. Genetic study confirms the diagnosis.The treatment usually consists of hematopoietic stem cell transplantationin association with immunosuppressive drugs. Prenatal diagnosis is very importantto allow parents to have healthy children
Workshop on Basic Concepts and Clinical Applications of Flow Cytometry for the Diagnosis of Primary Immunodeficiencies Diseases
No full textPrimary immunodeficiencies (PIDs) are a group of diseases that cause susceptibility to
Infections, autoimmunity and malignancy. PIDs consist of more than 130 inherited
conditions. They are estimated to occur from 1 in 10,000 to 1 in 2,000 live births. The
clinical spectrum of PID is highly variable. The incidence of PIDs in Sudan is uncertain
because of a lack of a national registry system. However, the high ratio of
consanguineous marriages makes PID a relatively frequent condition. Pediatricians or
residents of pediatric clinics are faced with patients with different complaints and signs.
Simple laboratory tests are helpful in the screening and diagnosis of a large number of
PID cases. If initial laboratory tests are inconclusive, in the case of a suspected PID,
further sophisticated tests are warranted. Early diagnosis and treatment, before severe
complications and tissue damage develop, haveshown to improve both morbidity and
mortality. However, lack of awareness about immunodeficiency can cause misdiagnosis
and severe complications
Mycobacterium tuberculosis Virulent Factor ESAT-6 Drives Macrophage Differentiation Toward the Pro-inflammatory M1 Phenotype and Subsequently Switches It to the Anti-inflammatory M2 Phenotype
No full textTuberculosis, a human infectious disease caused by Mycobacterium tuberculosis (M.tb), is still a major cause of morbidity and mortality worldwide. The success of M.tb as a pathogen relies mainly on its ability to divert the host innate immune responses. One way by which M.tb maintains a persistent infection in a “silent” granuloma is to inhibit inflammation and induce an immunoregulatory phenotype in host macrophages (MΦs). However, M.tb effectors governing the switch of MΦs from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype remain to be determined. The Early Secreted Antigenic Target 6 kDa or ESAT-6, has been implicated in the virulence and pathogenesis of tuberculosis. Here, we investigated roles of ESAT-6 in MΦ differentiation and polarization. We found that treatment of human monocytes with ESAT-6 did not interfere with differentiation of M1 MΦs. However, ESAT-6 promoted differentiation of M0 and M2 MΦs toward the M1 phenotype, as indicated by secretion of pro-inflammatory cytokines IL-6, IL-12, and TNF-α, and induction of a typical M1 transcriptional signature. Interestingly, we found that ESAT-6 switched terminal full activation of M1 polarized MΦs to the M2 phenotype. Indeed, in the pro-inflammatory M1 MΦs, ESAT-6 was able to inhibit IL-12 and TNF-α secretion and stimulate that of IL-10. Moreover, gene expression profiling of these cells showed that ESAT-6 induced downregulation of M1 MΦ cell surface molecules CD80 and CD86, transcription factors IRF5 and c-MAF, cytokines IL-12, IL-10, and IL-6, as well as chemokines CXCL10 and CXCL1. Overall, our findings suggest ESAT-6 as being one of the effectors used by M.tb to induce the pro-inflammatory M1 phenotype at the primo-infection; a prerequisite step to promote granuloma formation and subsequently drive the phenotype switch of MΦ polarization from M1 to M2 at a later stage of the infection. Our study improves current knowledge regarding mechanisms of virulence of M.tb and may be helpful to develop novel tools targeting ESAT-6 for a better and more efficient treatment of tuberculosis
Consanguinity and Primary Immunodeficiencies
No full textInternational audiencePrimary immunodeficiencies (PIDs) are a heterogeneous group of genetic disorders caused by defects in the immune system that predispose patients to infections, autoimmune diseases, lymphoproliferation and malignancies. Most PIDs are inherited in an autosomal recessive pattern; therefore, they are more common in areas with high rates of consanguineous marriage. Reports about PIDs from these areas have demonstrated a peculiar prevalence of more severe forms of diseases compared to other regions, and patients born to consanguineous parents have increased rates of morbidity and mortality compared to other patients. Individuals at high risk of having a child with a PID who wish to have a healthy child have limited options, these include prenatal diagnosis and pre-implantation genetic diagnosis. However, these options require a collaborative team of specialists and may not always be implemented due to geographic, religious, financial or social factors. The recent introduction of newborn-screening programs for a number of T and B lymphocyte deficiencies will facilitate early diagnosis and therapeutic interventions, which may include hematopoietic stem cell transplantation and intravenous immunoglobulin treatment. There is a need for the implementation of strategies to increase public awareness of the health risks associated with consanguineous marriage. It should be stressed that genetic counseling should be an important component of the care of patients with PIDs as well as their families. (C) 2014 S. Karger AG, Base
Toward personalization of asthma treatment according to trigger factors
No full textAsthma is a severe and chronic disabling disease affecting more than 300 million people worldwide. Although in the past few drugs for the treatment of asthma were available, new treatment options are currently emerging, which appear to be highly effective in certain subgroups of patients. Accordingly, there is a need for biomarkers that allow selection of patients for refined and personalized treatment strategies. Recently, serological chip tests based on microarrayed allergen molecules and peptides derived from the most common rhinovirus strains have been developed, which may discriminate 2 of the most common forms of asthma, that is, allergen- and virus-triggered asthma. In this perspective, we argue that classification of patients with asthma according to these common trigger factors may open new possibilities for personalized management of asthma.Fil: Niespodziana, Katarzyna. Vienna University of Technology; AustriaFil: Borochova, Kristina. Vienna University of Technology; AustriaFil: Pazderova, Petra. Vienna University of Technology; AustriaFil: Schlederer, Thomas. Vienna University of Technology; AustriaFil: Astafyeva, Natalia. Saratov State Medical University; RusiaFil: Baranovskaya, Tatiana. Belarusian Medical Academy of Post Diploma Studies; BielorrusiaFil: Barbouche, Mohamed Ridha. Institut Pasteur de Tunis; TúnezFil: Beltyukov, Evgeny. Ural State Medical University; RusiaFil: Berger, Angelika. Vienna University of Technology; AustriaFil: Borzova, Elena. Russian Medical Academy of Continuous Professional Education; RusiaFil: Bousquet, Jean. MACVIA; Francia. Humboldt-Universität zu Berlin; AlemaniaFil: Bumbacea, Roxana S.. University of Medicine and Pharmacy "Carol Davila"; RumaniaFil: Bychkovskaya, Snezhana. Krasnoyarsk Medical University; RusiaFil: Caraballo, Luis. Universidad de Cartagena; ColombiaFil: Chung, Kian Fan. Imperial College London; Reino Unido. MRC and Asthma UK Centre in Allergic Mechanisms of Asthma; Reino UnidoFil: Custovic, Adnan. Imperial College London; Reino Unido. MRC and Asthma UK Centre in Allergic Mechanisms of Asthma; Reino UnidoFil: Docena, Guillermo H.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Eiwegger, Thomas. University Of Toronto. Hospital For Sick Children; CanadáFil: Evsegneeva, Irina. Sechenov First Moscow State Medical University; RusiaFil: Emelyanov, Alexander. North-Western Medical University; RusiaFil: Errhalt, Peter. University Hospital Krems and Karl Landsteiner University of Health Sciences; AustriaFil: Fassakhov, Rustem. Kazan Federal University; RusiaFil: Fayzullina, Rezeda. Bashkir State Medical University; RusiaFil: Fedenko, Elena. NRC Institute of Immunology FMBA of Russia; RusiaFil: Fomina, Daria. Sechenov First Moscow State Medical University; RusiaFil: Gao, Zhongshan. Zhejiang University; ChinaFil: Giavina Bianchi, Pedro. Universidade de Sao Paulo; BrasilFil: Gotua, Maia. David Tvildiani Medical University; GeorgiaFil: Greber Platzer, Susanne. Vienna University of Technology; AustriaFil: Hedlin, Gunilla. Karolinska Huddinge Hospital. Karolinska Institutet; Sueci
- …
