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dc.contributor.author
Almejún, María Belén
dc.contributor.author
Campos, Bárbara Carolina
dc.contributor.author
Patiño, Virginia
dc.contributor.author
Galicchio, Miguel
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Zelazko, Marta
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Oleastro, Matías
dc.contributor.author
Oppezzo, Pablo
dc.contributor.author
Danielian, Silvia
dc.date.available
2018-07-18T19:33:19Z
dc.date.issued
2017-03
dc.identifier.citation
Almejún, María Belén; Campos, Bárbara Carolina; Patiño, Virginia; Galicchio, Miguel; Zelazko, Marta; et al.; Noninfectious complications in patients with pediatric-onset common variable immunodeficiency correlated with defects in somatic hypermutation but not in class-switch recombination; Mosby-Elsevier; Journal of Allergy and Clinical Immunology; 139; 3; 3-2017; 913-922
dc.identifier.issn
0091-6749
dc.identifier.uri
http://hdl.handle.net/11336/52609
dc.description.abstract
Background Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by impaired immunoglobulin production and usually presents with a normal quantity of peripheral B cells. Most attempts aiming to classify these patients have mainly been focused on T- or B-cell phenotypes and their ability to produce protective antibodies, but it is still a major challenge to find a suitable classification that includes the clinical and immunologic heterogeneity of these patients. Objective In this study we evaluated the late stages of B-cell differentiation in a heterogeneous population of patients with pediatric-onset CVID to clinically correlate and assess their ability to perform somatic hypermutation (SHM), class-switch recombination (CSR), or both. Methods We performed a previously reported assay, the restriction enzyme hotspot mutation assay (IgκREHMA), to evaluate in vivo SHM status. We amplified switch regions from genomic DNA to investigate the quality of the double-strand break repairs in the class-switch recombination process in vivo. We also tested the ability to generate immunoglobulin germline and circle transcripts and to upregulate the activation-induced cytidine deaminase gene through in vitro T-dependent and T-independent stimuli. Results Our results showed that patients could be classified into 2 groups according to their degree of SHM alteration. This stratification showed a significant association between patients of group A, severe alteration, and the presence of noninfectious complications. Additionally, 60% of patients presented with increased microhomology use at switched regions. In vitro activation revealed that patients with CVID behaved heterogeneously in terms of responsiveness to T-dependent stimuli. Conclusions The correlation between noninfectious complications and SHM could be an important tool for physicians to further characterize patients with CVID. This categorization would help to improve elucidation of the complex mechanisms involved in B-cell differentiation pathways.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Mosby-Elsevier
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Class-Switch Recombination
dc.subject
Common Variable Immunodeficiency
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Hypermutation
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Pediatric
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Somatic Hypermutation
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Switch
dc.subject.classification
Inmunología
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Noninfectious complications in patients with pediatric-onset common variable immunodeficiency correlated with defects in somatic hypermutation but not in class-switch recombination
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-07-17T20:50:54Z
dc.journal.volume
139
dc.journal.number
3
dc.journal.pagination
913-922
dc.journal.pais
Estados Unidos
dc.journal.ciudad
St Louis
dc.description.fil
Fil: Almejún, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: Campos, Bárbara Carolina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: Patiño, Virginia. Instituto Pasteur; Uruguay
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Fil: Galicchio, Miguel. Hospital de Niños Víctor J. Vilela; Argentina
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Fil: Zelazko, Marta. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: Oleastro, Matías. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: Oppezzo, Pablo. Instituto Pasteur; Uruguay
dc.description.fil
Fil: Danielian, Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.journal.title
Journal of Allergy and Clinical Immunology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1016/j.jaci.2016.08.030
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0091674916310545


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