Jeanette H. W. Leusen^1,2, Arthur J. Verhoeven¹ and Dirk Roos^1,3

¹ Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands.

²Department of Pediatrics, Emma's Children Hospital, Academic Medical Center, Amsterdam, The Netherlands.

Received 04/15/96; Accepted 05/05/96; On-line 07/01/96

The importance of the NADPH oxidase in human host defense is exemplified by patients suffering from chronic granulomatous disease (CGD). CGD is an immunodeficiency syndrome characterized clinically by severe recurrent bacterial and fungal infections. These infections typically consist of pneumonia, lymphadenitis and abcesses that involve the liver, the subcutaneous tissues and the bones. Control of the infections can usually be achieved with appropriate antibiotic therapy, but eradication of the infecting organisms is often slow and attained with great difficulty. The persistence of micro-organisms, often within the phagosomal vacuoles of neutrophils or macrophages, is the stimulus to a chronic inflammatory state with granuloma formation.

Biochemically, CGD is characterized by the inability of phagocytic leukocytes (neutrophils, eosinophils, monocytes and macrophages) to activate the NADPH oxidase and to generate the reactive oxygen compounds needed for the killing of phagocytosed micro-organisms (10, 11). Therefore, the most common pathogens encountered in CGD patients are catalase-positive organisms, because catalase prevents the CGD phagocytes from using microbial hydrogen peroxide for killing these pathogens. Predominant are Staphylococcus aureus, Aspergillus species and a variety of gram-negative enteric bacilli. CGD is a rare disease, with an estimated incidence of 1 in about 250,000 individuals, without any ethnic preference. It usually manifests itself in early childhood and is predominantly found in boys (12). CGD is a very heterogeneous disorder; clinically because of many antimicrobial systems that can partially compensate for the defect in oxygen-dependent killing systems, and biochemically because of the complicated genetic origin of CGD (13). Characterizing the mutations that lead to CGD is important for improved diagnosis and treatment of CGD patients, but also provides a better understanding of the functional domains within the oxidase components.