X-linked chronic granulomatous disease (XL-CGD), a rare primary immunodeficiency due to a defect in the gp91<sup>phox</sup> NADPH oxidase subunit, results in recurrent, severe infection, inflammation, and autoimmunity.
Through manipulation of the balance between oxidative and reductive capacities in the phagosome-principally by modulating NADPH oxidase (NOX2) and γ-interferon-inducible lysosomal thiol reductase (GILT) activities-studies have demonstrated changes to antigen processing patterns leading to modified repertoires of antigenic peptides available for presentation, and subsequently, altered disease progression in T cell-driven autoimmunity.
This was also observed in individuals with chronic granulomatous disease, who lack NADPH oxidase activity but still develop autoimmunity and type I IFN signatures.
The Ncf1 gene, encoding the P47(PHOX) protein that regulates production of reactive oxygen species (ROS) by the phagocyte NADPH oxidase (NOX2) complex, is associated with autoimmunity and arthritis severity in rats.
Neutrophil cytosolic factor 1, p47phox (NCF1) is a component of the leukocyte NADPH oxidase complex mediating formation of reactive oxygen intermediates (ROI) which play an important role in host defense and autoimmunity.
A case-control study of rheumatoid arthritis identifies an associated single nucleotide polymorphism in the NCF4 gene, supporting a role for the NADPH-oxidase complex in autoimmunity.