Reference

natureNature Communications 6, 7335.

Authors

Virginia C. Rodríguez-Cortez, Lucia del Pino-Molina, Javier Rodríguez-Ubreva, Laura Ciudad, David Gómez-Cabrero, Carlos Company, José M. Urquiza, Jesper Tegnér, Carlos Rodríguez-Gallego, Eduardo López-Granados and Esteban Ballestar

Abstract

Common variable immunodeficiency (CVID), the most frequent primary immunodeficiency characterized by loss of B-cell function, depends partly on genetic defects, and epigenetic changes are thought to contribute to its aetiology. Here we perform a high-throughput DNA methylation analysis of this disorder using a pair of CVID-discordant MZ twins and show predominant gain of DNA methylation in CVID B cells with respect to those from the healthy sibling in critical B lymphocyte genes, such as PIK3CD, BCL2L1, RPS6KB2, TCF3 and KCNN4. Individual analysis confirms hypermethylation of these genes. Analysis in naive, unswitched and switched memory B cells in a CVID patient cohort shows impaired ability to demethylate and upregulate these genes in transitioning from naive to memory cells in CVID. Our results not only indicate a role for epigenetic alterations in CVID but also identify relevant DNA methylation changes in B cells that could explain the clinical manifestations of CVID individuals.

Description

La inmunodeficiencia común variable (CVID) se caracteriza por niveles bajos de inmunoglobulinas y una mayor susceptibilidad a infecciones. La mayoría de los pacientes con CVID presentan infecciones recurrentes. Aunque la CVID tiene un componente genético, se acepta que existen otros mecanismos que determinan la aparición de la enfermedad. En este estudio, la comparación de los patrones epigenéticos en linfocitos B de una pareja de gemelos idénticos discordantes para esta enfermedad, ha permitido identificar la existencia de alteraciones epigenéticas en el gemelo con la inmunodeficiencia que no están presentes en el gemelo sano. El análisis de la metilación de dichos genes en linfocitos en diferentes estados de maduración en una cohorte de pacientes de CVID respecto a controles sanos mostró que sus células B han perdido parcialmente la capacidad de desmetilar dichos genes durante el proceso de generar linfocitos maduros.

 

groupoArticuloMesSept2015

 

REFERENCIA DEL GRUPO INVESTIGADOR

 

El grupo de Cromatina y Enfermedad del Institut d'Investigació Biomèdica de Bellvitge (IDIBELL) está dirigido por el Dr Esteban Ballestar y centra su actividad investigadora en el estudio de mecanismos de desregulación epigenética en el sistema inmune, especialmente en el contexto de enfermedad autoinmune, inmunodeficiencia y en distintos modelos de diferenciación relevantes en enfermedades del sistema inmune. En los últimos años el laboratorio ha publicado diversos trabajos relacionados con la adquisición de alteraciones epigenéticas en distintos tipos celulares de enfermedades autoinmunes como el lupus eritematoso sistémico y la artritis reumatoide. http://www.idibell.cat/modul/chromatin-and-disease/en

Descárgate este artículo aquí.

Did you publish an interesting article recently?

Send it through our application form and we will contact you. Age limit: 32.

The selected articles will participate at the Award to the best article of young people of the SEBBM which will be given during SEBBM conference, that will take place at Spain (free registration, travel and accommodation).

More articles of the month

Functional optimization of broadly neutralizing HIV-1 antibody 10E8 by promoting membrane interactions

01-03-2018

El anticuerpo 10E8 representa uno de los anticuerpos anti-VIH con mayor cobertura de neutralización y potencia descrito a día de hoy. Su epítopo se localiza en una región próxima a...

Read more

Molecular mechanism for the subversion of the retromer coat by the Legionella effector RidL

01-02-2018

La legionelosis o enfermedad del legionario es una neumonía potencialmente fatal, causada por la bacteria Legionella pneumophila. Durante la infección, la bacteria trasloca un gran número de proteínas, llamadas efectores...

Read more

Late rDNA Condensation Ensures Timely Cdc14 Release and Coordination of Mitotic Exit Signaling with Nucleolar Segregation

01-01-2018

El nucléolo, además de su función esencial en la biogénesis de los ribosomas, juega también un papel importante en múltiples procesos celulares. Así, en este orgánulo se mantienen secuestradas proteínas clave para...

Read more

Inactivation of Capicua in adult mice causes T-cell lymphoblastic lymphoma

01-12-2017

CIC (also known as Capicua) is a transcriptional repressor negatively regulated by RAS/MAPK signaling. Whereas the functions of Cic have been well characterized in Drosophila, little is known about its...

Read more

Physical proximity of chromatin to nuclear pores prevents harmful R loop accumulation contributing to maintain genome stability

01-11-2017

During transcription, the mRNA may hybridize with DNA, forming an R loop, which can be physiological or pathological, constituting in this case a source of genomic instability. To understand the...

Read more

Whi7 is an unstable cell-cycle repressor of the Start transcriptional program

01-10-2017

Start is the main decision point in eukaryotic cell cycle in which cells commit to a new round of cell division. It involves the irreversible activation of a transcriptional program...

Read more

CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation

01-09-2017

In germinal centres (GC) mature B cells undergo intense proliferation and immunoglobulin gene modification before they differentiate into memory B cells or long-lived plasma cells (PC). GC B-cell-to-PC transition involves...

Read more

Catalytic Cycle of the N-Acetylglucosaminidase NagZ from Pseudomonas aeruginosa

01-08-2017

The N-acetylglucosaminidase NagZ of Pseudomonas aeruginosa catalyzes the first cytoplasmic step in recycling of muropeptides, cell-wall-derived natural products. This reaction regulates gene expression for the β-lactam resistance enzyme, β-lactamase. The...

Read more

Crebbp loss cooperates with Bcl2 overexpression to promote lymphoma in mice.

01-07-2017

CREBBP is targeted by inactivating mutations in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Here, we provide evidence from transgenic mouse models that Crebbp deletion results in deficits...

Read more

Local amplifiers of IL-4Rα-mediated macrophage activation promote repair in lung and liver

01-06-2017

The type 2 immune response controls helminth infection and maintains tissue homeostasis but can lead to allergy and fibrosis if not adequately regulated. We have discovered local tissue-specific amplifiers of...

Read more

Protector Members