David B. Lewis

Publication Details

  • Adult-onset presentations of genetic immunodeficiencies: genes can throw slow curves CURRENT OPINION IN INFECTIOUS DISEASES Nelson, K. S., Lewis, D. B. 2010; 23 (4): 359-364


    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.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.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.

    View details for DOI 10.1097/QCO.0b013e32833bc1b0

    View details for Web of Science ID 000279397600010

    View details for PubMedID 20581672

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