title: Autoimmunity and cystatin SA1 deficiency behind chronic mucocutaneous candidiasis in autoimmune polyendocrine syndrome type 1.
abstract: 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.
authors.affiliation: Translational Immunology Unit, Dept. of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Lindh
authors.forename: Johan
authors.initials: J
authors.lastname: Brännström
authors.forename: Petra
authors.initials: P
authors.lastname: Jones
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wermeling
authors.forename: Signe
authors.initials: S
authors.lastname: Hässler
authors.forename: Corrado
authors.initials: C
authors.lastname: Betterle
authors.forename: Ben Zion
authors.initials: BZ
authors.lastname: Garty
authors.forename: Mats
authors.initials: M
authors.lastname: Stridsberg
authors.forename: Björn
authors.initials: B
authors.lastname: Herrmann
authors.forename: Mikael C I
authors.initials: MC
authors.lastname: Karlsson
authors.forename: Ola
authors.initials: O
authors.lastname: Winqvist
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000378:metabolism; D015551:Autoimmunity; D002178:Candidiasis, Chronic Mucocutaneous / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006131:Growth Inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D008297:Male; D020409:Molecular Motor Proteins / Q000276:immunology; D018995:Myosin Heavy Chains / Q000276:immunology; D016884:Polyendocrinopathies, Autoimmune / Q000150:complications / Q000235:genetics / Q000276:immunology*; D012463:Saliva / Q000378:metabolism; D055333:Salivary Cystatins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D006131:Growth Inhibitors; D007070:Immunoglobulin A; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D055333:Salivary Cystatins; D018995:Myosin Heavy Chains