Chronic mucocutaneous candidiasis: Immunologic studies of three generations of a single family

doi:10.1016/0002-9343(79)90635-1

The American Journal of Medicine

Volume 67, Issue 6, December 1979, Pages 948-959

https://doi.org/10.1016/0002-9343(79)90635-1 Get rights and content

Abstract

A family consisting of eight members in three generations (age 10 months to 53 years) affected with chronic mucocutaneous candidiasis was studied along with three Unaffected relatives. Dermatophytosis, loss of teeth and recurrent viral infections were present in some members. Results of tests for endocrinologic, muscle or liver disease, thymoma, iron deficiency, antitissue antibodies and malabsorption were normal in all patients.

Antibody function and levels, B cell counts, serum complement, leukocyte enzymes, chemotaxis, phagocytosis and adherence were normal in all members. Plasma inhibitors to lymphocyte transformation and leukocyte inhibitory factor were not found. No unique HLA haplotype or antigen segregated in this family.

Evaluation of cell-mediated immunity revealed total cutaneous anergy in three of eight whereas four of the other five had negative lymphocyte transformation and skin tests to Candida but responded normally to other antigens. Leukocyte inhibitory factor was not produced to Candida antigen in all four patients tested. T cell counts were within normal limits in all.

Extensive evaluation of all limbs of the immune system in this family revealed a defect in cell-mediated immunity to Candida that appeared to be inherited as a dominant characteristic.

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Citation Excerpt :
Published studies suggest that autosomal dominant CMC (MIM 114580) may be common among patients who do not have APECED. A family reported by Sams et al. (1979) and Jorizzo et al. (1980) demonstrated autosomal transmission of CMC, with no recognized endocrinopathy, in three children and four grandchildren of an affected subject. In another family, an 11-year-old boy, his sister, and her daughter had CMC without reported endocrine abnormalities (Canales et al. 1969).
We describe a large family in which a combination of chronic mucocutaneous candidiasis (fungal infections of the skin, nails, and mucous membranes) and thyroid disease segregate as an autosomal dominant trait with reduced penetrance. The family includes (a) four members with both candidiasis and thyroid disease, (b) five members, including one pair of phenotype-concordant MZ twins, with candidiasis only, and (c) three members with thyroid disease only. A whole-genome scan using DNA samples from 20 members of the family identified a candidate linkage region on chromosome 2p. By sampling additional individuals and genotyping supplementary markers, we established linkage to a region of ∼15 cM bounded by D2S367 and D2S2240 and including seven adjacent markers consistent with linkage. With a penetrance estimate of .8, which was based on pedigree and affected status, the peak two-point LOD score was 3.70 with marker D2S2328, and the peak three-point LOD score was 3.82. This is the first linkage assignment of a dominant locus for mucocutaneous candidiasis.
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Chronic mucocutaneous candidiasis is a heterogeneous immunodeficiency syndrome characterized by recurrent candidal infections of the skin, nails, and mucous membranes. The syndrome can be associated with autoimmune conditions, especially endocrine disorders. Typically, inheritance is autosomal recessive, and abnormal T-cellmediated immunity is thought to be the underlying deficit. We describe a 27–year-old man with chronic mucocutaneous candidiasis inherited in an autosomal dominant fashion, in whom both lymphocyte blastogenesis and delayedtype skin reactivity to Candida antigens were normal. No– table features of the case include autoimmune hemolytic anemia, probable hypoparathyroidism, and hypogonadal hypogonadism.
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Chronic mucocutaneous candidiasis is characterized by impaired clearance of fungal infections and results in colonization and infections of the mucosa or skin, predominantly with Candida albicans.¹,² A variety of clinical conditions, such as infection with the human immunodeficiency virus or the use of corticosteroids, favor the development of chronic mucocutaneous candidiasis, but the disease may also be a primary immunodeficiency arising from unknown genetic defects.¹,³ In chronic mucocutaneous candidiasis, the most common infections are due to C. albicans; however, patients may also have an increased susceptibility to dermatophytes.¹,³ Severe complications rarely develop in patients with chronic . . .

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^☆: This study was supported by a grant from the National Institute of Arthritis, Metabolic and Digestive Diseases (5-R01-AM20031-03), from the National Institute of Allergic and Infectious Diseases (A1 13770-02), from the National Institute for Dental Research (5-R01-DE03738-06), a training grant from the National Institute of Arthritis, Metabolic and Digestive Diseases (5T32-AM-G7015-04), Public Health Service Research Grant RP-46 of the General Clinical Research Centers Branch of Divisions of Research Sources and a grant from the Medical Research Service of the Veterans Administration Service.

¹: From the Departments of Dermatology and Medicine, The University of North Carolina, Chapel Hill, North Carolina; the Divisions of Rheumatology, Dermatology and Immunology, Duke University, Durham, North Carolina.

²: From the Division of Infectious Diseases, The University of Texas Health Sciences Center at San Antonio, San Antonio, Texas.

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Clinical studyChronic mucocutaneous candidiasis: Immunologic studies of three generations of a single family☆

Abstract

Immunochemistry

Clin Immunol Immunopathol

Am J Med

Cell Immunol

Clin Immunol Immunopathol

Lancet

Lancet

Clin Immunol Immunopathol

J Invest Dermatol

A simple microcytotoxicity test

Transplantation

Complement technology

Tests of immune function

A method for dinitrochlorobenzene contact sensitization

N Engl J Med

Binding of sheep erythrocytes to human lymphocytes. A probable marker of T-lymphocytes

Scand J Immunol

Human lymphocyte-sheep erythrocyte rosette formation: some characteristics of the interaction

Clin Immunol Immunopathol

Isolation of mononuclear cells and granulocytes from human blood

Scand J Clin Lab Invest

Human mononuclear leukocyte chemotaxis. A quantitative assay for humoral and cellular factors

J Immunol

A human mononuclear leukocyte chemotactic factor: characterization, specificity and kinetics of production by homologous leukocytes

J Immunol

Biological Activities of Complement

Biologic and biochemical activities of continuous macrophage cell ines P388DT and J774.1

J Immunol

Tuberculin-induced migration inhibition of human peripheral leukocytes in agarose medium

Acta Allergol

Tests of immune function

Immunocytochemical identification of azurophilic and specific granule markers in the giant granules of Chediak-Higashi neutrophils

N Engl J Mod

Mannan antigenemia in the diagnosis of invasive Candida infections

J Clin Invest

Clinical application of counterimmunoelectrophoresis in detection of Candida serum precipitins

J Lab Clin Med

Severe Candidal infections. Clinical perspective, immune defense mechanisms, and current concepts of therapy

Ann Intern Med

Further observations on the Swiss type of agammaglobulinemia (alymophocytosis). The effect of syngeneic bone marrow colls

N Engl J Med

Clinical study
Chronic mucocutaneous candidiasis: Immunologic studies of three generations of a single family☆