PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jexpmedHomeThe Rockefeller University PressThis articleEditorsContactInstructions for AuthorsThis issue
 

An external file that holds a picture, illustration, etc.
Object name is jem.2072iti3fig1.jpg

APS-I patients harbored autoantibodies against IFN-α, IL-17A, IL-17F, and IL-22.

Two new studies suggest why patients with the autoimmune disorder APS-I are susceptible to chronic yeast infections. According to Puel et al. and Kisand et al., APS-I patients produce autoantibodies against microbe-fighting cytokines—making this disorder one of a small handful of diseases enhanced by antibodies that target cytokines.

The yeast infection, known as chronic mucocutaneous candidiasis, usually develops before other symptoms of APS-I. The infection is perplexing given that many autoimmune disorders are characterized by exaggerated Th17 cell responses, which produce cytokines like interleukin (IL)-17A, IL-17F, and IL-22 that fight microbial pathogens at mucosal surfaces. On the contrary, here the teams suggest that APS-I patients have diminished Th17 activity due to autoantibodies against these signature cytokines. Kisand et al. found that cultured progenitor cells from APS-I patients produced less IL-17F and IL-22 in response to yeast antigens or polyclonal stimuli. And although some cells made less IL-17A as well, cytokine levels varied overall, likely reflecting variation in genetic, environmental, or clinical backgrounds.

The paucity of cytokines correlated with the presence of autoantibodies against IL-17A, IL-17F, and IL-22. These autoantibodies blocked or neutralized the cytokines but, according to Kisand et al., did not obstruct Th17 cell differentiation. Other inflammatory cytokines were unaffected, with the exception of interferon (IFN)-a, which is known to be blocked by autoantibodies in APS-I patients. However, APS-I patients do not appear prone to recurrent viral infections despite neutralization of this antiviral cytokine—perhaps because other IFNs compensate.

How these autoantibodies arise remains a mystery. Infection was not the trigger, because APS-I patients without candidiasis produced them as well. The authors suggest that their origin may be due to mutations in the gene underlying APS-I, which disrupt the autoimmune regulator AIRE. AIRE normally prevents autoreactive T cells from leaving the thymus, but a direct connection between the AIRE disruption and anti-cytokine antibodies remains to be seen.


Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press