Familial chronic muco-cutaneous candidiasis.

Wells, R.S.; Higgs, Janet M.; Macdonald, Angus; Valdimarsson, H.; Holt, P. J.

doi:10.1136/jmg.9.3.302

Cited by 94 publications

(38 citation statements)

References 18 publications

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“…We also deciphered the genetic basis of another Mendelian "hole" in host defense, familial chronic mucocutaneous candidiasis (CMC), which was first described clinically in the late 1960s and early 1970s (Table 4) (68,69). Unexpectedly, whereas investigations of MSMD led us to defects of Th1 cells, our studies of CMC led to the discovery of mutations in another arm of the effector CD4 + T-cell response, Th17 cells.…”

Section: Chronic Mucocutaneous Candidiasismentioning

confidence: 99%

Severe infectious diseases of childhood as monogenic inborn errors of immunity

Casanova

2015

Proc. Natl. Acad. Sci. U.S.A.

201

163

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This paper reviews the developments that have occurred in the field of human genetics of infectious diseases from the second half of the 20th century onward. In particular, it stresses and explains the importance of the recently described monogenic inborn errors of immunity underlying resistance or susceptibility to specific infections. The monogenic component of the genetic theory provides a plausible explanation for the occurrence of severe infectious diseases during primary infection. Over the last 20 y, increasing numbers of life-threatening infectious diseases striking otherwise healthy children, adolescents, and even young adults have been attributed to single-gene inborn errors of immunity. These studies were inspired by seminal but neglected findings in plant and animal infections. Infectious diseases typically manifest as sporadic traits because human genotypes often display incomplete penetrance (most genetically predisposed individuals remain healthy) and variable expressivity (different infections can be allelic at the same locus). Infectious diseases of childhood, once thought to be archetypal environmental diseases, actually may be among the most genetically determined conditions of mankind. This nascent and testable notion has interesting medical and biological implications.

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Section: Chronic Mucocutaneous Candidiasismentioning

confidence: 99%

Severe infectious diseases of childhood as monogenic inborn errors of immunity

Casanova

2015

Proc. Natl. Acad. Sci. U.S.A.

201

163

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“…Patients with autosomal dominant (AD) hyper-IgE syndrome (HIES), caused by heterozygous dominant negative mutations of STAT3, display fewer infections, and patients with autosomal recessive (AR) autoimmune polyendocrine syndrome type 1 (APS-1) are not prone to other infections (2, 3). Finally, rare patients with inherited but idiopathic forms of CMC, referred to as CMC disease (CMCD), have been described since the late 1960s (4)(5)(6)(7)(8). These patients may display isolated CMC, but they often also display cutaneous staphylococcal disease (nonetheless referred to as CMCD) or other infectious and/or autoimmune clinical manifestations (syndromic CMCD).…”

Section: Significancementioning

confidence: 99%

Genetic, immunological, and clinical features of patients with bacterial and fungal infections due to inherited IL-17RA deficiency

Lévy

Okada

Béziat

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

151

127

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Chronic mucocutaneous candidiasis (CMC) is defined as recurrent or persistent infection of the skin, nails, and/or mucosae with commensalCandidaspecies. The first genetic etiology of isolated CMC—autosomal recessive (AR) IL-17 receptor A (IL-17RA) deficiency—was reported in 2011, in a single patient. We report here 21 patients with complete AR IL-17RA deficiency, including this first patient. Each patient is homozygous for 1 of 12 different IL-17RA alleles, 8 of which create a premature stop codon upstream from the transmembrane domain and have been predicted and/or shown to prevent expression of the receptor on the surface of circulating leukocytes and dermal fibroblasts. Three other mutant alleles create a premature stop codon downstream from the transmembrane domain, one of which encodes a surface-expressed receptor. Finally, the only known missense allele (p.D387N) also encodes a surface-expressed receptor. All of the alleles tested abolish cellular responses to IL-17A and -17F homodimers and heterodimers in fibroblasts and to IL-17E/IL-25 in leukocytes. The patients are currently aged from 2 to 35 y and originate from 12 unrelated kindreds. All had their first CMC episode by 6 mo of age. Fourteen patients presented various forms of staphylococcal skin disease. Eight were also prone to various bacterial infections of the respiratory tract. Human IL-17RA is, thus, essential for mucocutaneous immunity toCandidaandStaphylococcus, but otherwise largely redundant. A diagnosis of AR IL-17RA deficiency should be considered in children or adults with CMC, cutaneous staphylococcal disease, or both, even if IL-17RA is detected on the cell surface.

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“…The clinical and immunological features of CMC and their potential relationship to mannan are described. (196,198), or responses to in vivo and in vitro tests of cell-mediated immune function (185), but none of these schemes has been accepted as satisfactory. Although the heterogeneity of CMC may defy strict classification, such efforts have continued.…”

Section: Immunosuppressive Effects Of Mannanmentioning

confidence: 99%

Candida mannan: chemistry, suppression of cell-mediated immunity, and possible mechanisms of action

et al. 1991

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The ability of Candida albicans to establish an infection involves multiple components of this fungal pathogen, but its ability to persist in host tissue may involve primarily the immunosuppressive property of a major cell wall glycoprotein, mannan. Mannan and oligosaccharide fragments of mannan are potent inhibitors of cell-mediated immunity and appear to reproduce the immune deficit of patients with the mucocutaneous form of candidiasis. However, neither the exact structures of these inhibitory species nor their mechanisms of action have yet been clearly defined. Different investigators have proposed that mannan or mannan catabolites act upon monocytes or suppressor T lymphocytes, but research from unrelated areas has provided still other possibilities for consideration. These include interference with cytokine activities, lymphocyte-monocyte interactions, and leukocyte homing. To stimulate further research of the immunosuppressive property of C. albicans mannan, we have reviewed (i) the relationship of mannan to other antigens and virulence factors of the fungus; (ii) the chemistry of mannan, together with methods for preparation of mannan and mannan fragments; and (iii) the historical evidence for immunosuppression by Candida mannan and the mechanisms currently proposed for this property; and (iv) we have speculated upon still other mechanisms by which mannan might influence host defense functions. It is possible that understanding the immunosuppressive effects of mannan will provide clues to novel therapies for candidiasis that will enhance the efficacy of both available and future anti-Candida agents.

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Familial chronic muco-cutaneous candidiasis.

Cited by 94 publications

References 18 publications

Severe infectious diseases of childhood as monogenic inborn errors of immunity

Severe infectious diseases of childhood as monogenic inborn errors of immunity

Genetic, immunological, and clinical features of patients with bacterial and fungal infections due to inherited IL-17RA deficiency

Candida mannan: chemistry, suppression of cell-mediated immunity, and possible mechanisms of action

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