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Extrapulmonary Aspergillus infection in patients with CARD9 deficiency.

Publication ,  Journal Article
Rieber, N; Gazendam, RP; Freeman, AF; Hsu, AP; Collar, AL; Sugui, JA; Drummond, RA; Rongkavilit, C; Hoffman, K; Henderson, C; Clark, L ...
Published in: JCI Insight
October 20, 2016

Invasive pulmonary aspergillosis is a life-threatening mycosis that only affects patients with immunosuppression, chemotherapy-induced neutropenia, transplantation, or congenital immunodeficiency. We studied the clinical, genetic, histological, and immunological features of 2 unrelated patients without known immunodeficiency who developed extrapulmonary invasive aspergillosis at the ages of 8 and 18. One patient died at age 12 with progressive intra-abdominal aspergillosis. The other patient had presented with intra-abdominal candidiasis at age 9, and developed central nervous system aspergillosis at age 18 and intra-abdominal aspergillosis at age 25. Neither patient developed Aspergillus infection of the lungs. One patient had homozygous M1I CARD9 (caspase recruitment domain family member 9) mutation, while the other had homozygous Q295X CARD9 mutation; both patients lacked CARD9 protein expression. The patients had normal monocyte and Th17 cell numbers in peripheral blood, but their mononuclear cells exhibited impaired production of proinflammatory cytokines upon fungus-specific stimulation. Neutrophil phagocytosis, killing, and oxidative burst against Aspergillus fumigatus were intact, but neither patient accumulated neutrophils in infected tissue despite normal neutrophil numbers in peripheral blood. The neutrophil tissue accumulation defect was not caused by defective neutrophil-intrinsic chemotaxis, indicating that production of neutrophil chemoattractants in extrapulmonary tissue is impaired in CARD9 deficiency. Taken together, our results show that CARD9 deficiency is the first known inherited or acquired condition that predisposes to extrapulmonary Aspergillus infection with sparing of the lungs, associated with impaired neutrophil recruitment to the site of infection.

Duke Scholars

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Published In

JCI Insight

DOI

ISSN

2379-3708

Publication Date

October 20, 2016

Volume

1

Issue

17

Start / End Page

e89890

Location

United States

Related Subject Headings

  • Neutrophils
  • Neutrophil Infiltration
  • Mutation
  • Male
  • Lung
  • Humans
  • Homozygote
  • Child
  • CARD Signaling Adaptor Proteins
  • Aspergillus fumigatus
 

Citation

APA
Chicago
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Rieber, N., Gazendam, R. P., Freeman, A. F., Hsu, A. P., Collar, A. L., Sugui, J. A., … Lionakis, M. S. (2016). Extrapulmonary Aspergillus infection in patients with CARD9 deficiency. JCI Insight, 1(17), e89890. https://doi.org/10.1172/jci.insight.89890
Rieber, Nikolaus, Roel P. Gazendam, Alexandra F. Freeman, Amy P. Hsu, Amanda L. Collar, Janyce A. Sugui, Rebecca A. Drummond, et al. “Extrapulmonary Aspergillus infection in patients with CARD9 deficiency.JCI Insight 1, no. 17 (October 20, 2016): e89890. https://doi.org/10.1172/jci.insight.89890.
Rieber N, Gazendam RP, Freeman AF, Hsu AP, Collar AL, Sugui JA, et al. Extrapulmonary Aspergillus infection in patients with CARD9 deficiency. JCI Insight. 2016 Oct 20;1(17):e89890.
Rieber, Nikolaus, et al. “Extrapulmonary Aspergillus infection in patients with CARD9 deficiency.JCI Insight, vol. 1, no. 17, Oct. 2016, p. e89890. Pubmed, doi:10.1172/jci.insight.89890.
Rieber N, Gazendam RP, Freeman AF, Hsu AP, Collar AL, Sugui JA, Drummond RA, Rongkavilit C, Hoffman K, Henderson C, Clark L, Mezger M, Swamydas M, Engeholm M, Schüle R, Neumayer B, Ebel F, Mikelis CM, Pittaluga S, Prasad VK, Singh A, Milner JD, Williams KW, Lim JK, Kwon-Chung KJ, Holland SM, Hartl D, Kuijpers TW, Lionakis MS. Extrapulmonary Aspergillus infection in patients with CARD9 deficiency. JCI Insight. 2016 Oct 20;1(17):e89890.

Published In

JCI Insight

DOI

ISSN

2379-3708

Publication Date

October 20, 2016

Volume

1

Issue

17

Start / End Page

e89890

Location

United States

Related Subject Headings

  • Neutrophils
  • Neutrophil Infiltration
  • Mutation
  • Male
  • Lung
  • Humans
  • Homozygote
  • Child
  • CARD Signaling Adaptor Proteins
  • Aspergillus fumigatus