Chronic granulomatous disease (CGD) is associated with defective function of the NADPH-oxidase system in
conjunction with phagocytic defects which leads to granuloma formation and serious infectious complications. This is
often associated with significant morbidity and mortality. The association of defective phagocyte function with other
coincidental immune defects is unknown. Defects in innate pathways seen with CGD, including complement systems, and
toll-like and dectin receptor pathways, have not been described before. We present the case of a 2-year old male patient
hospitalized with recurrent pneumonia, a non-healing skin ulcer, necrotizing lung granulomas, and epididymo-orchitis.
Defective neutrophil chemiluminescence was detected by dihydrorhodamine (DHR) testing. Further evaluation
demonstrated characteristic molecular mutations of CYBB consistent with CGD. Immune evaluation demonstrated
polyclonal hyperglobulinemia, but a greatly reduced mannose binding lectin (MBL) level. Six biallelic polymorphisms in
MBL gene and its promoter were analyzed using Light CyclerTM Real-time PCR assay. The LXPA/LYPB haplotype of
MBL was detected in our patient; the latter is the defective haplotype associated with low MBL levels. Due to the
implications for innate immunity and the protection against bacterial, viral, and fungal infections provided by MBL, a
deficiency of this protein may have disastrous consequences on the long term outcomes of CGD. MBL deficiency can also
complicate other disorders affecting the immune system, significantly increasing the risk of infection in such patients.
Further studies looking at the frequency and implications of MBL deficiency in CGD are needed.
Keywords: Chronic granulomatous disease, complement, immune deficiency, innate immunity, mannose binding protein
deficiency, NADPH oxidase, opportunistic infections, phagocyte
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Published on: 24 April, 2012
Page: [222 - 226]