Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2010 Aug;23(4):359-64.
doi: 10.1097/QCO.0b013e32833bc1b0.

Adult-onset presentations of genetic immunodeficiencies: genes can throw slow curves

Katharine S Nelson  1 , David B Lewis
Affiliations
Review

Adult-onset presentations of genetic immunodeficiencies: genes can throw slow curves

Katharine S Nelson et al. Curr Opin Infect Dis. 2010 Aug.

Abstract

Purpose of review: The molecular and genetic mechanisms behind adult presentations of primary immunodeficiency diseases are examined, with particular emphasis on cases where this was heralded by severe, recurrent, or opportunistic infection.

Recent findings: A detailed analysis over the last two decades of the relationship between genotype and clinical phenotype for a number of genetic immunodeficiencies has revealed multiple mechanisms that can account for the delayed presentation of genetic disorders that typically present in childhood, including hypomorphic gene mutations and X-linked gene mutations with age-related skewing in random X-chromosome inactivation. Adult-onset presentations of chronic granulomatous disease, X-linked agammaglobulinemia, IL-12/Th1/IFN-gamma and IL-23/Th17/IL-17 pathway defects, and X-linked lymphoproliferative disorder are used to illustrate these mechanisms. Finally, certain genetic types of common variable immunodeficiency are used to illustrate that inherited null mutations can take decades to manifest immunologically.

Summary: Both genetic mechanisms and environmental factors can account for adult-onset infectious and noninfectious complications as manifestations of disorders that are typically present in childhood. This emphasizes the potential complexity in the relationship between genotype and phenotype with natural human mutations.

PubMed Disclaimer

References

    1. Sicherer SH, Winkelstein JA. Primary immunodeficiency diseases in adults. JAMA. 1998;279:58–61. - PubMed
    1. Patel SY, Ding L, Brown MR, Lantz L, Gay T, Cohen S, Martyak LA, Kubak B, Holland SM. Anti-IFN-gamma autoantibodies in disseminated nontuberculous mycobacterial infections. J Immunol. 2005;175:4769–4776. - PubMed
    1. Puel A, Doffinger R, Natividad A, Chrabieh M, Barcenas-Morales G, Picard C, Cobat A, Ouachee-Chardin M, Toulon A, Bustamante J, et al. Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. J Exp Med. 207:291–297. - PMC - PubMed

    2. ••An important study that found an association between antibodies against IL-17 and IL-22, which are characteristically produced by Th17 cells, and chronic mucocutaneous candidiasis, including in adult patients. This substantially extends the importance of anti-cytokine antibodies in human in provoking opportunistic infections.

    1. Marodi L, Casanova JL. Novel primary immunodeficiencies relevant to internal medicine: novel phenotypes. J Intern Med. 2009;266:502–506. - PubMed

    2. •This useful review highlights several examples of where genetic or autoantibody-mediated immunodeficiencies can present with non-infectious complications in adults.

    1. Notarangelo LD, Fischer A, Geha RS, Casanova JL, Chapel H, Conley ME, Cunningham-Rundles C, Etzioni A, Hammartrom L, Nonoyama S, et al. Primary immunodeficiencies: 2009 update. J Allergy Clin Immunol. 2009;124:1161–1178. - PMC - PubMed

Publication types

MeSH terms