Defective B-cell proliferation and maintenance of long-term memory in patients with chronic granulomatous disease - 05/03/15
, Paolo Palma, MD, PhD a, ⁎, ‡ , Iyadh Douagi, PhD d, ⁎, ‡ Abstract |
Background |
Chronic granulomatous disease (CGD) is a primary immune deficiency characterized by a defect in reactive oxygen species production. Although the effect of CGD mainly reflects on the phagocytic compartment, B-cell responses are also impaired in patients with CGD.
Objective |
We sought to investigate how defective gp91phox expression in patients with CGD and CGD carriers might affect the B-cell compartment and maintenance of long-term memory.
Methods |
We studied the B-cell compartment of patients with CGD in terms of phenotype and ability to produce reactive oxygen species and proliferate on stimuli differently directed to the B-cell receptor and Toll-like receptor 9. We further studied their capacity to maintain long-term memory by measuring cellular and serologic responses to measles.
Results |
We show that the memory B-cell compartment is impaired among patients with CGD, as indicated by reduced total (CD19+CD27+) and resting (CD19+CD27+CD21+) memory B cells in parallel to increased naive (CD19+CD27−IgD+) B-cell frequencies. Data on CGD carriers reveal that such alterations are related to gp91phox expression. Moreover, proliferative capabilities of B cells on selective in vitro stimulation of B-cell receptor or Toll-like receptor 9 pathways were reduced in patients with CGD compared with those seen in age-matched healthy control subjects. Significantly lower measles-specific antibody levels and antibody-secreting cell numbers were also observed, indicating a poor ability to maintain long-term memory in these patients.
Conclusion |
Altogether, our data suggest that patients with CGD present a defective B-cell compartment in terms of frequencies of memory B cells, response to in vitro stimulation, and maintenance of long-term antigen-specific memory.
Le texte complet de cet article est disponible en PDF.Key words : Chronic granulomatous disease, B cell, proliferation, long-term memory, measles, memory B-cell compartment, reactive oxygen species deficiency
Abbreviations used : Anti-Ig, ASC, BCR, CGD, HC, NADPH, PMA, PWM, ROS, TLR
Plan
| Supported by grants obtained from the Bambino Gesù Children's Hospital and the Karolinska Institutet. Also supported by Cell-PID HEALTH F5-2010-261387, EUROCGD project (ERA-NET E-Rare: “European research projects on rare diseases”), Italian Ministry of Health (Progetto Giovani Ricercatori GR-2008-57 to A.F.). |
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| Disclosure of potential conflict of interest: This study was supported by grants obtained from the Bambino Gesù Children's hospital and from the Karolinska Institutet. A. Finocchi's institution has received funding from Progetto Giovani Ricercatori. A. Aiuti's institution has received funding from the European Union. The rest of the authors declare that they have no other relevant conflicts of interest. |
Vol 135 - N° 3
P. 753 - mars 2015 Retour au numéro
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