A Controlled Trial of Interferon Gamma to Prevent Infection in Chronic Granulomatous Disease

Gallin, John I.; Malech, Harry L.; Curnutte, W. J. T.; Quie, P. G.; Jaffe, Howard S.; Ezkowitz, R. A. B.

doi:10.1056/nejm199102213240801

Cited by 723 publications

(86 citation statements)

References 35 publications

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“…A multifaceted therapeutic approach has been responsible for the greatly improved prognosis in CGD. The key elements of the current therapy include the following: avoidance of certain sources of pathogens, use of prophylactic trimethoprim-sulfamethoxazole, early use of antifungal drugs, surgical drainage or debridement when feasible, granulocyte transfusions for poorly responding infections, and the use of prophylactic recombinant human interferon-γ [8, 10, 36, 37, 38]. Prophylactic antibiotics and interferon-γ have reduced bacterial infections, but there is also the danger of life-threatening fungal infections which are not altered by trimethoprim-sulfamethoxazole prophylaxis [36].…”

Section: Discussionmentioning

confidence: 99%

Chronic Granulomatous Disease: A Clinical Survey of 41 Patients from the Iranian Primary Immunodeficiency Registry

Movahedi

Aghamohammadi

Rezaei

et al. 2004

Int Arch Allergy Immunol

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Background: Chronic granulomatous disease (CGD) represents a group of inherited disorders of the phagocytic system, involving recurrent infections at different sites, especially the respiratory system. The present study was accomplished in order to determine the clinical spectrum of Iranian patients with CGD. Methods: Forty-one patients (29 males and 12 females) with CGD, who had already been referred to two immunodeficiency referral centers in Iran, were reviewed during a 22-year period (1980–2002). Results: These patients belonged to 34 families, and 56% of them were consanguineous. The median age at the time of study was 12 years (3 months to 22 years). The median age at onset of symptoms was 4 months (1 month to 12 years), and the median diagnostic age was 5.5 years (2 months to 20 years), with a diagnostic delay of 3 years on average. The most common presenting complaint in our CGD patients was lymphadenopathy (seen in 11 patients, 26.8%). The most common manifestations of CGD (in descending order) were lymphadenopathy (75.6%), pulmonary infections (65.9%) and skin involvement (63.4%) during their illness, followed by gastrointestinal (56.1%), skeletal (29.3%), upper respiratory tract (26.8%) and central nervous system (2.4%) involvement. Conclusions: Early diagnosis of the disease is crucial. In view of the possibility of timely treatment, i.e. prophylactic treatment of infection, CGD should be excluded in any patient with unexplained infections or granulomas.

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Section: Discussionmentioning

confidence: 99%

Chronic Granulomatous Disease: A Clinical Survey of 41 Patients from the Iranian Primary Immunodeficiency Registry

Movahedi

Aghamohammadi

Rezaei

et al. 2004

Int Arch Allergy Immunol

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“…On the basis of these in vitro data, and results from a small study that indicated restoration of the oxidative burst in 2 patients with CGD who received subcutaneous IFN-γ [41], a randomized double-blind placebo-controlled study was conducted in the early 1990s to determine the efficacy of IFN-γ in patients with CGD [43]. In that trial, 128 patients with CGD were randomly assigned to receive IFN-γ or placebo 3 times per week.…”

Section: Ifn-γmentioning

confidence: 99%

“…Although the administration of IFN-γ therapy was found to be effective in patients with either X-linked or AR CGD, the effect was more substantial in those with X-linked disease, particularly younger patients with X-linked CGD. In addition, IFN-γ was well tolerated in all populations, and the adverse-effect rate was minimal [43]. …”

Section: Ifn-γmentioning

confidence: 99%

Prevention of Infectious Complications in Patients With Chronic Granulomatous Disease

Slack

Thomsen

2018

Journal of the Pediatric Infectious Diseases Society

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Chronic granulomatous disease (CGD) is a primary immunodeficiency that confers a markedly increased risk of bacterial and fungal infections caused by certain opportunistic pathogens. Current evidence supports the use of prophylactic antibacterial, antifungal, and immunomodulatory therapies designed to prevent serious or life-threatening infections in patients with CGD. In this review, we discuss current strategies for the prevention of infections in children and adults with CGD and the evidence that supports those strategies. In addition, we address current challenges and opportunities for future research in this important area.

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“…Currently, infectious prophylaxis with trimethoprim-sulfamethoxazole and the aggressive treatment of acute infections has improved survival [23]. Subcutaneous injections of interferon-γ three times a week has greatly reduced the number of life-threatening infections for many patients [24]. Granulomas may respond to low-dose steroid therapy [25], but some require surgical resection.…”

Section: Clinical Manifestations and Current Therapymentioning

confidence: 99%

Gene Therapy for Chronic Granulomatous Disease

Goebel

Dinauer

2003

Acta Haematol

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Identification of gene mutations responsible for leukocyte dysfunction along with the application of gene transfer technology has made genetic correction of such disorders possible. Much of the research into molecular therapy for inherited disorders of phagocytes has been focused on chronic granulomatous disease (CGD). CGD results from mutations in any one of the four genes encoding essential subunits of respiratory burst NADPH oxidase, the enzyme complex required for the production of reactive oxygen intermediates in phagocytes. The absence of phagocyte oxidants results in a predisposition to recurrent bacterial and fungal infections and inflammatory granulomas in CGD patients, associated with significant morbidity and mortality. Allogeneic bone marrow transplantation can cure CGD, but transplant-related toxicity and the limited availability of matched donors have restricted its wider application. Because the gene defects causing CGD are known, and CGD is a stem cell disorder treatable by marrow transplantation, CGD has emerged as a promising disease for somatic gene therapy targeted at the hematopoietic system. Multiple reports have demonstrated the reconstitution of NADPH oxidase activity by gene transfer to human CGD marrow and cell lines cultured in vitro. CGD mouse models have been developed by gene disruption, and preclinical studies on these animals using recombinant retroviral vectors have demonstrated reconstitution of functionally normal neutrophils and increased resistance to pathogens such as Aspergillus fumigatus, Burkholderia cepacia and Staphylococcus aureus. Although the results of these murine studies are encouraging, human phase-I clinical studies in CGD patients have yet to produce clinically beneficial numbers of corrected neutrophils for extended periods. Efforts to improve gene transfer efficiency into human hematopoietic stem cells and to increase engraftment of transduced stem cells are ongoing.

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A Controlled Trial of Interferon Gamma to Prevent Infection in Chronic Granulomatous Disease

Abstract: For patients with chronic granulomatous disease, interferon gamma therapy is an effective and well-tolerated treatment that reduces the frequency of serious infections.

Cited by 723 publications

References 35 publications

Chronic Granulomatous Disease: A Clinical Survey of 41 Patients from the Iranian Primary Immunodeficiency Registry

Chronic Granulomatous Disease: A Clinical Survey of 41 Patients from the Iranian Primary Immunodeficiency Registry

Prevention of Infectious Complications in Patients With Chronic Granulomatous Disease

Gene Therapy for Chronic Granulomatous Disease

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