Abstract
Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by defects in the genes encoding any of the NADPH oxidase components responsible for the respiratory burst of phagocytic leukocytes. CGD is a genetically heterogeneous disease with an X-linked recessive (XR-CGD) form caused by mutations in the CYBB gene encoding the gp91phox protein, and an autosomal recessive (AR-CGD) form caused by mutations in the CYBA, NCF1, NCF2, or NCF4 genes encoding p22phox, p47phox, p67phox, and p40phox, respectively. Patients suffering from this disease are susceptible to severe life-threatening bacterial and fungal infections and excessive inflammation characterized by granuloma formation in any organ, for instance, the gastrointestinal and genitourinary tract. An early diagnosis of and the prompt treatment for these conditions are crucial for an optimal outcome of affected patients. To prevent infections, CGD patients should receive lifelong antibiotics and antifungal prophylaxis. These two measures, as well as newer more effective antimicrobials, have significantly modified the natural history of CGD, resulting in a remarkable change in overall survival, which is now around 90%, reaching well into adulthood. At present, hematopoietic stem cell transplantation (HSCT) is the only definitive treatment that can cure CGD and reverse organ dysfunction. Timing, donor selection, and conditioning regimens remain the key points of this therapy. In recent years, gene therapy (GT) for XR-CGD has been proposed as an alternative to HSCT for CGD patients without a matched donor. After the failure of the first trials performed with retroviral vectors, some groups have proposed the use of regulated SIN-lentiviral vectors targeting gp91phox expression in myeloid cells to increase the safety and efficacy of the GT protocols.
| Original language | English |
|---|---|
| Journal | Pediatric Allergy and Immunology |
| DOIs | |
| Publication status | Accepted/In press - 2016 |
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Keywords
- Chronic granulomatous disease
- Genetic counseling
- Hyperinflammation
- Infections
- Molecular diagnosis
- NADPH oxidase
- Therapy
ASJC Scopus subject areas
- Immunology and Allergy
- Pediatrics, Perinatology, and Child Health
- Immunology
Cite this
Chronic granulomatous disease : Clinical, molecular, and therapeutic aspects. / Chiriaco, Maria; Salfa, Irene; Di Matteo, Gigliola; Rossi, Paolo; Finocchi, Andrea.
In: Pediatric Allergy and Immunology, 2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Chronic granulomatous disease
T2 - Clinical, molecular, and therapeutic aspects
AU - Chiriaco, Maria
AU - Salfa, Irene
AU - Di Matteo, Gigliola
AU - Rossi, Paolo
AU - Finocchi, Andrea
PY - 2016
Y1 - 2016
N2 - Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by defects in the genes encoding any of the NADPH oxidase components responsible for the respiratory burst of phagocytic leukocytes. CGD is a genetically heterogeneous disease with an X-linked recessive (XR-CGD) form caused by mutations in the CYBB gene encoding the gp91phox protein, and an autosomal recessive (AR-CGD) form caused by mutations in the CYBA, NCF1, NCF2, or NCF4 genes encoding p22phox, p47phox, p67phox, and p40phox, respectively. Patients suffering from this disease are susceptible to severe life-threatening bacterial and fungal infections and excessive inflammation characterized by granuloma formation in any organ, for instance, the gastrointestinal and genitourinary tract. An early diagnosis of and the prompt treatment for these conditions are crucial for an optimal outcome of affected patients. To prevent infections, CGD patients should receive lifelong antibiotics and antifungal prophylaxis. These two measures, as well as newer more effective antimicrobials, have significantly modified the natural history of CGD, resulting in a remarkable change in overall survival, which is now around 90%, reaching well into adulthood. At present, hematopoietic stem cell transplantation (HSCT) is the only definitive treatment that can cure CGD and reverse organ dysfunction. Timing, donor selection, and conditioning regimens remain the key points of this therapy. In recent years, gene therapy (GT) for XR-CGD has been proposed as an alternative to HSCT for CGD patients without a matched donor. After the failure of the first trials performed with retroviral vectors, some groups have proposed the use of regulated SIN-lentiviral vectors targeting gp91phox expression in myeloid cells to increase the safety and efficacy of the GT protocols.
AB - Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by defects in the genes encoding any of the NADPH oxidase components responsible for the respiratory burst of phagocytic leukocytes. CGD is a genetically heterogeneous disease with an X-linked recessive (XR-CGD) form caused by mutations in the CYBB gene encoding the gp91phox protein, and an autosomal recessive (AR-CGD) form caused by mutations in the CYBA, NCF1, NCF2, or NCF4 genes encoding p22phox, p47phox, p67phox, and p40phox, respectively. Patients suffering from this disease are susceptible to severe life-threatening bacterial and fungal infections and excessive inflammation characterized by granuloma formation in any organ, for instance, the gastrointestinal and genitourinary tract. An early diagnosis of and the prompt treatment for these conditions are crucial for an optimal outcome of affected patients. To prevent infections, CGD patients should receive lifelong antibiotics and antifungal prophylaxis. These two measures, as well as newer more effective antimicrobials, have significantly modified the natural history of CGD, resulting in a remarkable change in overall survival, which is now around 90%, reaching well into adulthood. At present, hematopoietic stem cell transplantation (HSCT) is the only definitive treatment that can cure CGD and reverse organ dysfunction. Timing, donor selection, and conditioning regimens remain the key points of this therapy. In recent years, gene therapy (GT) for XR-CGD has been proposed as an alternative to HSCT for CGD patients without a matched donor. After the failure of the first trials performed with retroviral vectors, some groups have proposed the use of regulated SIN-lentiviral vectors targeting gp91phox expression in myeloid cells to increase the safety and efficacy of the GT protocols.
KW - Chronic granulomatous disease
KW - Genetic counseling
KW - Hyperinflammation
KW - Infections
KW - Molecular diagnosis
KW - NADPH oxidase
KW - Therapy
UR - http://www.scopus.com/inward/record.url?scp=84955449090&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84955449090&partnerID=8YFLogxK
U2 - 10.1111/pai.12527
DO - 10.1111/pai.12527
M3 - Article
AN - SCOPUS:84955449090
JO - Pediatric Allergy and Immunology
JF - Pediatric Allergy and Immunology
SN - 0905-6157
ER -