Chronic granulomatous disease (CGD) is an inherited disease, fatally impairing children's ability to survive infections. The cause is a lack of NADPH oxidase activity in the phagocytes that can not generate reactive oxygen species, most notably superoxide anion. Recurring bacterial and fungal infections are the consequences. Patients with CGD also suffer from chronic inflammatory conditions, most prominently granuloma formation in hollow viscera.

In mice with chronic granulomatous disease (CGD), a superoxide-dependent step of the tryptophan metabolism is blocked in the kynurenine pathway. The mice suffered from lethal pulmonary aspergillosis causing unrestricted T-cell reactivity, increased production of interleukin (IL)-17, defective regulatory T-cell activity and acute inflammatory lung injury. Luigina Romani and her team from the University of Perugia in Italy observed that complete cure and reversal of the hyperinflammatory phenotype succeeded when the kynurenine distal to the blockade in the pathway was replaced.

An effective therapy required co-administration of recombinant interferon-gamma (IFN-gamma) and was able to restore production of downstream immunoactive metabolites. The therapy also succeeded in releasing regulatory Vγ4+γδ and Foxp3+αβ T-cells.

In absence of reactive oxygen species, the hyperinflammatory phenotype associated with NADPH oxidase deficiencies is stronger, caused by a dysfunctional kynurenine pathway of tryptophan catabolism. The phenotype can be cured by reactivating the pathway downstream of the superoxide-dependent step.

Related antibodies on antibodies-online.com:

Tryptophan

Kynurenine

T-cells

Interleukin-17 (IL-17)

Interferon-gamma

Foxp3

NADPH

NADPH oxidase organizer 1

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