Autoimmunity and cystatin SA1 deficiency behind chronic mucocutaneous candidiasis in autoimmune polyendocrine syndrome type 1

J Autoimmun. 2013 May;42:1-6. doi: 10.1016/j.jaut.2012.10.001. Epub 2012 Nov 1.


Patients with the monogenic disease autoimmune polyendocrine syndrome type I (APSI) develop autoimmunity against multiple endocrine organs and suffer from chronic mucocutaneous candidiasis (CMC), a paradoxical complication with an unknown mechanism. We report here that saliva from APSI patients with CMC is defective in inhibiting growth of Candida albicans in vitro and show reduced levels of a salivary protein identified as cystatin SA1. In contrast, APSI patients without CMC express salivary cystatin SA1 and can inhibit C. albicans to the same extent as healthy controls. We evaluated the anti-fungal activity of cystatin SA1 and found that synthesized full length cystatin SA1 efficiently inhibits growth of C. albicans in vitro. Moreover, APSI patients exhibit salivary IgA autoantibodies recognizing myosin-9, a protein expressed in the salivary glands, thus linking autoimmunity to cystatin SA1 deficiency and CMC. This data suggests an autoimmune mechanism behind CMC in APSI and provides rationale for evaluating cystatin SA1 in antifungal therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / metabolism
  • Autoimmunity
  • Candidiasis, Chronic Mucocutaneous / etiology
  • Candidiasis, Chronic Mucocutaneous / genetics
  • Candidiasis, Chronic Mucocutaneous / immunology*
  • Female
  • Genetic Predisposition to Disease
  • Growth Inhibitors / genetics
  • Growth Inhibitors / immunology
  • Growth Inhibitors / metabolism*
  • Humans
  • Immunoglobulin A / metabolism
  • Male
  • Molecular Motor Proteins / immunology
  • Myosin Heavy Chains / immunology
  • Polyendocrinopathies, Autoimmune / complications
  • Polyendocrinopathies, Autoimmune / genetics
  • Polyendocrinopathies, Autoimmune / immunology*
  • Saliva / metabolism
  • Salivary Cystatins / genetics
  • Salivary Cystatins / immunology
  • Salivary Cystatins / metabolism*
  • Young Adult


  • Autoantibodies
  • Growth Inhibitors
  • Immunoglobulin A
  • MYH9 protein, human
  • Molecular Motor Proteins
  • Salivary Cystatins
  • Myosin Heavy Chains

Supplementary concepts

  • Autoimmune polyendocrinopathy syndrome, type 1