Saturday, July 23, 2016

Immune system of APS1/APECED patients maintains "tolerance" by targeting disease-modifying self-cytokines

AIRE deficiency defines APS1/APECED syndrome for which autoimmune polyendocrinopathy and chronic mucocutaneous candidiasis are signature phenotypes. 

For this study, the authors (associated with biotech company ImmunoQure) screened serum samples from APS1/APECED patients, their healthy relatives or unrelated healthy volunteers. Using a ProtoArray displaying ~ 9000 recombinant human proteins or protein fragments, the  researchers found that, among other things, sera from APS1/APECED patients showed significant reactivity to IFN, IL-17 and IL-10 family cytokines.

These hypermutated anti-cytokine antibodies could efficiently neutralize corresponding cytokines both in vitro in a cell reporter assay and in vivo in an ear inflammation assay.

Remarkably, among APS1/APECED patients, those with high titres of anti-cytokine neutralizing antibodies did not progress to type I diabetes (T1D) even though both population groups harbored anti-islet auto-antibodies (to GAD65).

In summary, this study indicates that immune system of APS1/APECED patients could maintain "tolerance" to some degree by targeting disease-modifying "self" cytokines.    

David Usharauli

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