Table 1. Syndromic CMC and CMCD: clinical and immunological phenotype and molecular defects/genetic etiologies.
| Disease | Frequency of CMC | Other infections | Associated symptoms | Immunological phenotype | Gene | Inheritance | Refs |
|---|---|---|---|---|---|---|---|
| Syndromic CMC | |||||||
| HIES | 85% | Staphylococcus, Aspergillus | Eczema, scoliosis, pneumatocoele, hyperextensibility, dysmorphic facial features, retention of primary teeth | Increased serum IgE, eosinophilia, decreased IL-17-producing T cells | STAT3 | AD | 14, 17, 19, 20, 78 |
| APECED | 70–98% | Ectodermal dysplasia, autoimmune dysfunciton of parathyroid and adrenal glands, alopecia | Neutralizing antibodies against IL-17A, IL-17F and/or IL-22 | AIRE | AR | 9, 23, 24, 25 | |
| CARD9 deficiency | 35–86% | Dermatophytes, Candida, brain abscess | Decreased IL-17-producing T cells, impairment of C. albicans-killing by neutrophils | CARD9 | AR | 7, 8, 18, 26 | |
| IL-12Rβ1 and IL-12p40 deficiency | 6–25% | Mycobacterium, Salmonella | Decreased IL-17-producing T cells, impaired IL-12 signaling | IL12RB1 IL12B | AR | 10, 11, 16, 27, 28, 29 | |
| STAT1 gain-of-function | 98% | Bacteria, viruses, fungi, mycobacteria | Aneurysm, autoimmune diseases, endocrine diseases | Decreased IL-17-producing T cells, decreased switched memory B cells | STAT1 | AD | 30, 31, 32, 33, 34, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66 |
| RORγT deficiency | 6/7 (86%) | Mycobacterium | Lack of peripheral lymph node, thymic hypoplasia | Defect of MAIT, type 1 NKT, IL-17-producing T cells, impaired antigen-specific IFN-γ production | RORC | AR | 12 |
| CMCD | |||||||
| IL-17RA deficiency | 3/3 (100%) | Staphylococcus | No response to IL-17A, IL-17E and IL-17F | IL17RA | AR | 38, 72 | |
| IL-17RC deficiency | 3/3 (100%) | No response to IL-17A and IL-17F | IL-17RC | AR | 40 | ||
| IL-17F deficiency | 5/7 (70%) | Impaired IL-17F and IL-17A/F function | IL17F | AD | 38, 71 | ||
| ACT1 deficiency | 2/2 (100%) | Staphylococcus | No response to IL-17A, IL-17E, and IL-17F | TRAF3IP2 | AR | 39 | |
Abbreviations: AD, autosomal-dominant; APECED, autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy; AR, autosomal-recessive; CARD9, caspase recruitment domain-containing protein 9; CMC, chronic mucocutaneous candidiasis; CMCD, CMC disease; HIES, hyper IgE syndrome; IFN-γ, interferon gamma; IL, interleukin; RORγT, retinoic acid-related orphan receptor γT.