Residual NADPH Oxidase and Survival in Chronic Granulomatous Disease

Kuhns, Douglas B.; Alvord, W. Gregory; Heller, Theo; Feld, Jordan J.; Pike, Kristen; Marciano, Beatriz E.; Uzel, Gülbû; Ravin, Suk See De; Priel, Debra A. Long; Soule, Benjamin P.; Zarember, Kol A.; Malech, Harry L.; Holland, Steven M.; Gallin, John I.

doi:10.1056/nejmoa1007097

Cited by 511 publications

(426 citation statements)

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“…1,2 As a consequence, phagocytes of patients affected by CGD are unable to kill ingested microorganisms, resulting in augmented susceptibility to recurrent life-threatening pyogenic infections. [3][4][5][6] Although CGD is primarily recognized as an oxidative deficiency of the phagocytic compartment, key cellular pathways, including lymphocyte function, were also shown to link to ROS production. 7,8 Furthermore, patients affected by CGD have been described to present lower frequencies of circulating memory B cells, 9,10 with an intact humoral immunologic memory.…”

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confidence: 99%

Defective B-cell proliferation and maintenance of long-term memory in patients with chronic granulomatous disease

Cotugno

Finocchi

Cagigi

et al. 2015

Journal of Allergy and Clinical Immunology

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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 gp91 phox 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 1 CD27 1 ) and resting (CD19 1 CD27 1 CD21 1 ) memory B cells in parallel to increased naive (CD19 1 CD27 2 IgD 1 ) B-cell frequencies. Data on CGD carriers reveal that such alterations are related to gp91 phox 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

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confidence: 99%

Defective B-cell proliferation and maintenance of long-term memory in patients with chronic granulomatous disease

Cotugno

Finocchi

Cagigi

et al. 2015

Journal of Allergy and Clinical Immunology

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“…Mechanistically, the level of residual superoxide production determines survival, at least in X-linked CGD (17). The rates of long term survival are higher in X-CGD patients with higher residual superoxide production and lower in those with lower rates.…”

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confidence: 99%

Chronic Granulomatous Disease

Holland

2009

Clinic Rev Allerg Immunol

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“…An essential function of NADPH oxidase-dependent ROI generation in neutrophils is microbial killing. Indeed, residual ROI production in neutrophils is known to be an important parameter for predicting favorable clinical course and survival of CGD [4]. On the other hands, the role of NADPH oxidase in monocytes/macrophages, both of which harbor gp91 phox expression, remains poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the functional diagnosis of CGD is usually based on the defective respiratory burst of PMNs as representative of leukocytes. Residual ROI production in neutrophils is known to be an important parameter for predicting clinical course and survival in CGD patients [4]. On the other hands, the effects of residual function in monocytes/macrophage lineage on clinical course in CGD patients are presently less clear.…”

Section: Introductionmentioning

confidence: 99%