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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Clinical, molecular, and cellular immunologic findings in patients with SP110-associated veno-occlusive disease with immunodeficiency syndrome
Journal of Allergy and Clinical Immunology, Volume 130, No. 3, Year 2012
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Description
Background: Mutations in the SP110 gene result in infantile onset of the autosomal recessive primary immunodeficiency disease veno-occlusive disease with immunodeficiency syndrome (VODI), which is characterized by hypogammaglobulinemia, T-cell dysfunction, and a high frequency of hepatic veno-occlusive disease. Objectives: We sought to further characterize the clinical features, B-lineage cellular immunologic findings, and molecular pathogenesis of this disorder in 9 patients with new diagnoses, including 4 novel mutations from families of Italian, Hispanic, and Arabic ethnic origin. Methods: Methods used include clinical review; Sanger DNA sequencing of the SP110 gene; determination of transfected mutant protein function by using immunofluorescent studies in Hep-2 cells; quantitation of B-cell subsets by means of flow cytometry; assessments of B-cell function after stimulation with CD40 ligand, IL-21, or both; and differential gene expression array studies of EBV-transformed B cells. Results: We confirm the major diagnostic criteria and the clinical utility of SP110 mutation testing for the diagnosis of VODI. Analysis of 4 new alleles confirms that VODI is caused by reduced functional SP110 protein levels. Detailed B-cell immunophenotyping demonstrated that Sp110 deficiency compromises the ability of human B cells to respond to T cell-dependent stimuli and differentiate into immunoglobulin-secreting cells in vitro. Expression microarray studies have identified pathways involved in B-lymphocyte differentiation and macrophage function. Conclusion: These studies show that a range of mutations in SP110 that cause decreased SP110 protein levels and impaired late B-cell differentiation cause VODI and that the condition is not restricted to the Lebanese population. © 2012 American Academy of Allergy, Asthma & Immunology.
Authors & Co-Authors
Cliffe, Simon T.
Australia, Sydney
Prince of Wales Hospital
Bloch, Donald B.
United States, Boston
Massachusetts General Hospital
Suryani, Santi
Australia, Sydney
Unsw Sydney
Kamsteeg, Erik Jan
Netherlands, Nijmegen
Radboud University Medical Center
Avery, Danielle T.
Australia, Sydney
Unsw Sydney
Palendira, Umaimainthan
Australia, Sydney
Unsw Sydney
Church, Joseph A.
United States, Los Angeles
Children's Hospital Los Angeles
Wainstein, Brynn K.
Australia, Sydney
Sydney Children's Hospital, Randwick
Trizzino, Antonino
Italy, Palermo
Ospedale Dei Bambini G. Di Cristina
Lefranc, Gérard
France, Montpellier
Igh Institut de Génétique Humaine
Akatchérian, Carlo Y.
Lebanon, Beirut
Hôtel-dieu de France Hospital
Megarbane, Andre
Lebanon, Beirut
Université Saint-joseph de Beyrouth
Gilissen, Christian
Netherlands, Nijmegen
Radboud University Medical Center
Moshous, Despina
France, Paris
Université Paris Cité
France, Paris
Hôpital Necker Enfants Malades
Reichenbach, Janine
Switzerland, Zurich
Universität Zürich
Misbah, Siraj A.
United Kingdom, Oxford
John Radcliffe Hospital
Salzer, Uli
Germany, Freiburg Im Breisgau
Universitätsklinikum Freiburg
Abinun, Mario A.
United Kingdom, Newcastle
Newcastle General Hospital
Ong, Peck Y.
United States, Los Angeles
Children's Hospital Los Angeles
Stepensky, Polina Y.
Israel, Jerusalem
Hadassah University Medical Centre
Ruga, Ezia Maria
Italy, Padua
Università Degli Studi Di Padova
Ziegler, J. B.
Australia, Sydney
Sydney Children's Hospital, Randwick
Wong, Melanie
Australia, Sydney
Sydney Children's Hospital, Randwick
Tangye, Stuart G.
Australia, Sydney
Unsw Sydney
Lindeman, Robert
Australia, Sydney
Prince of Wales Hospital
Buckley, Michael Francis
Australia, Sydney
Prince of Wales Hospital
Roscioli, Tony
Australia, Sydney
Prince of Wales Hospital
Australia, Sydney
Unsw Sydney
Statistics
Citations: 49
Authors: 27
Affiliations: 18
Identifiers
Doi:
10.1016/j.jaci.2012.02.054
ISSN:
00916749
e-ISSN:
10976825
Research Areas
Cancer
Genetics And Genomics
Study Design
Cross Sectional Study