Recurrent inflammatory aortic aneurysms in chronic mucocutaneous candidiasis with a gain-of-function STAT1 mutation

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections of the skin, nails, and oral mucosae caused by Candida albicans. CMC was initially thought to be benign, until squamous cell carcinoma and cerebral aneurysms were reported [ [1] Liu L. Okada S. Kong X.F. et al. Gain-of-function human STAT1 mutations impair IL-17 immunity and underlying chronic mucocutaneous candidiasis. J. Exp. Med. 2011; 208: 1635-1648 Crossref PubMed Scopus (606) Google Scholar ]. Signal transducer and activator of transcription 1 (STAT1) mediates the expression of a variety of genes, and this is thought to be important for cell viability in response to different cell stimuli and pathogens. In type 1 helper T cells (Th1), STAT1 plays a crucial role in IFN-γ transcription. Autosomal dominant STAT1 gain-of-function (GOF) mutations in the coiled-coil (CC) domain are associated with CMC and autoimmunity [ [1] Liu L. Okada S. Kong X.F. et al. Gain-of-function human STAT1 mutations impair IL-17 immunity and underlying chronic mucocutaneous candidiasis. J. Exp. Med. 2011; 208: 1635-1648 Crossref PubMed Scopus (606) Google Scholar ]. Although the STAT1 GOF mutation was associated with lethal cerebral aneurysms (4.2% in CMC) [ [1] Liu L. Okada S. Kong X.F. et al. Gain-of-function human STAT1 mutations impair IL-17 immunity and underlying chronic mucocutaneous candidiasis. J. Exp. Med. 2011; 208: 1635-1648 Crossref PubMed Scopus (606) Google Scholar ], little is known about large vessel aneurysms. Here, we present a case of CMC with a STAT1 GOF mutation with abdominal and thoracic aortic aneurysms (AAA and TAA) that carry significant morbidity and mortality. We found that CD4+CD25+FoxP3+ regulatory T cells (Treg) were decreased, whereas anti-inflammatory CD14++CD16+CD29+ intermediate monocytes were increased, in the peripheral blood. In a pathological examination of aorta, there were many infiltrated T and B lymphocytes, as well as monocytes/macrophages. We discuss the possible pathophysiology in aneurysm-prone patients.