Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) is a rare group of hereditary disorders which impair certain cells of the immune system. Phagocytes use strong oxidants called reactive oxygen species (ROS) to destroy ingested pathogens in a process called a “respiratory burst,” which is a rapid release of ROS that is crucial for the immune system to destroy pathogens. CGD typically arises from a mutation to the NADPH oxidase complex, a macromolecular complex comprised of several protein subunits that acts as the phagocyte’s factory for ROS (Lambeth 2004). CGD arises when NADPH oxidase is mutated, as phagocytes become unable to form ROS and cannot destroy foreign microbes after engulfing them. Instead, the immune system will form granulomata to seal up the foreign invaders: these granulomata tend to build up and cause symptomatic inflammation throughout the body (Bagaitkar et al. 2015; Chiriaco et al. 2015). CGD decreases the capacity of the body’s immune system to fight invading microorganisms, so patients with CGD are also predisposed to frequent and atypical infections (Chiriaco et al. 2015).

CGD is a documented result of over 20 different genetic mutations to any of the subunits of NADPH oxidase. These protein subunits assemble into the NADPH oxidase complex like pieces of a 3D puzzle (Figure 1). A mutation to any of these NADPH oxidase subunits may affect the efficiency of the complex in forming ROS or may even prevent the complex from assembling (Ueyama et al. 2011).

Figure 1: Diagram of certain protein subunits assembling into the NADPH oxidase complex. Mutation to any of these subunits is associated with CGD. O2- represents the ROS superoxide. Obtained from Google Images. <>

CGD is usually diagnosed in childhood, with 90% of cases diagnosed before 5 years of age (Chiriaco et al. 2015). Most patients present with characteristic chronic granuloma formation throughout the body caused by recurrent infection and gastrointestinal inflammation (Marciano et al. 2004). Individuals with CGD are typically placed on lifelong antibiotic regimens which are effective in combatting infection, especially with the development of potent antimicrobials over the last decade (Chiriaco et al. 2015). Granulomas however are chronically present in CGD patients and can be particularly dangerous if they obstruct and inflame the gastrointestinal tract (Song et al. 2011). Research pinpointing the IL-1 receptor as mediating chronic inflammation in CGD suggests that blocking the IL-1 receptor may treat these symptoms by reducing chronic inflammation (Luca et al. 2014).

Stem cell therapy is a potential cure for CGD. Hematopoietic or induced pluripotent stem cells of CGD patients have been manipulated by gene transfer, viral vectors, and CRISPR-Cas9 system to give rise to healthy phagocytes, which are able to perform respiratory burst (Becker et al. 1998; Chiriaco et al. 2014; Flynn et al. 2015). More research into the safety and efficacy of these treatments may allow the clinical application of gene therapy to cure CGD.

Image 1: Image of a granuloma surrounding Mycobacterium tuberculosis. CGD is characterized by the formation of chronic granulomata. Obtained from Google images. <>


2 Replies to “Chronic Granulomatous Disease”

  1. Well- researched and in depth explanation of the topic! The language was too scientific for the average lay person, I fear. The opening sentence was very well constructed. However, the use of terms such as phagocytes, reactive oxygen species, granulomata necessitates clearer definition improved comprehension of the topic. The use of acronyms and abbreviations is also challenging for the layperson – simpler pictures and terminology.

    1. Thanks for your input! I agree I may have glazed over explaining some of the more important components and substituted links to the Biochemistry Primer instead of fuller explanation. I’ll be sure to revise this page and simplify some of my language.

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