Neutrophil Oxidative Burst, Blood
Diagnosis of X-linked chronic granulomatous disease (CGD) in male patients <40 years of age or autosomal recessive CGD in male and female patients
Identification of X-linked CGD female carriers
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Chronic granulomatous disease (CGD) is a diverse group of hereditary (X-linked and autosomal recessive) immunodeficiencies with impaired neutrophil function. The X-linked form of CGD is caused by mutations in the CYBB gene encoding the gp91phox protein. The other 3 forms of CGD are autosomal recessive and due to mutations in the p22phox, p47phox and p67phox-encoding genes. The majority (70%) of CGD is X-linked, and patients are diagnosed in childhood and early adulthood. However, female carriers can become phenotypically symptomatic, particularly when they get older. Patients with CGD frequently present with recurrent bacterial infections, particularly of the skin, subcutaneous areas, or regional lymph nodes. Sinopulmonary infections also are common. The majority of infections in CGD are due to Staphylococcus aureus, Pseudomonas cepacia, Serratia marcescens, nocardia, and aspergillus.
Normal neutrophil function is dependent on a number of properties including migration toward the site of infection, phagocytosis, and microbicidal activity. While most patients with recurrent infections have normal neutrophils, a persistent infection that fails to respond to appropriate medical treatment or infection with an organism that is unusual in an otherwise normal host suggest a possible neutrophil function defect. Measuring the neutrophil oxidative burst indirectly assesses microbicidal activity.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Absent oxidative burst is consistent with chronic granulomatous disease (CGD).
Carriers for X-linked CGD will have 2 neutrophil populations: 1 population will have a normal oxidative burst and the second will demonstrate no oxidative burst.
Carriers of autosomal recessive CGD will have a normal oxidative burst and can only be identified by genetic testing (contact Mayo Medical Laboratories for referral testing information).
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test should not be used to identify carriers for autosomal recessive forms of chronic granulomatous disease (CGD). Genetic testing should be used to identify carriers of autosomal recessive CGD. Genetic testing should also be performed for females who do not show typical carrier pattern for X-linked CGD, but have male offspring or relatives with a confirmed diagnosis (flow cytometry and genetic testing) of X-linked CGD.
In males, this test is typically not indicated in patients >40 years of age. For questions about appropriate test selection, contact Mayo Medical Laboratories.
Before ordering this test, the clinician should investigate potential local causes of infection such as foreign bodies, skin maceration, repeated trauma, or congenital cysts, as well as assess the patient's environment for evidence of repeated infection. An investigation into allergic rhinitis and asthma is also recommended. If all the common causes are absent, the differential includes cystic fibrosis (even in adults), ciliary immobility syndrome, autoimmune disease such as Wegener granulomatosis, common variable immune deficiency, and finally CGD.
Clinical consultation by specialists in immune deficiency is recommended. For Mayo Clinic patients, referral to the Immune Deficiency Clinic in Adult and Pediatric Allergy is suggested.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
Hampton MB, Kettle AJ, Winterbourn CC: Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing. Blood 1998;92:3007-3017