Fc gamma receptor 3A polymorphism and risk for HIV-associated cryptococcal disease

Soma Rohatgi, Shruti Gohil, Mark H. Kuniholm, Hannah Schultz, Chad Dufaud, Kathryn L. Armour, Sheila Badri, Robbie B. Mailliard, Liise-anne Pirofski

Research output: Contribution to journalArticle

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Abstract

Cryptococcus neoformans is one of the most common causes of fungal disease in HIV-infected persons, but not all of those who are infected develop cryptococcal disease (CD). Although CD4 T cell deficiency is a risk factor for HIV-associated CD, polymorphisms of phagocytic Fc gamma receptors (FCGRs) have been linked to CD risk in HIV-uninfected persons. To investigate associations between FCGR2A 131 H/R and FCGR3A 158 F/V polymorphisms and CD risk in HIV-infected persons, we performed PCR-based genotyping on banked samples from 164 men enrolled in the Multicenter AIDS Cohort Study (MACS): 55 who were HIV infected and developed CD and a matched control group of 54 who were HIV infected and 55 who were HIV uninfected. Using additive and allelic statistical models for analysis, the high-affinity FCGR3A 158V allele was significantly associated with CD status after adjusting for race/ethnicity (odds ratio [OR], 2.1; P 0.005), as was the FCGR3A 158 VV homozygous genotype after adjusting for race/ethnicity, rate of CD4 T cell decline, and nadir CD4 T cell count (OR, 21; P 0.005). No associations between CD and FCGR2A 131 H/R polymorphism were identified. In binding studies, human IgG (hIgG)-C. neoformans complexes exhibited more binding to CHO-K1 cells expressing FCGR3A 158V than to those expressing FCGR3A 158F, and in cytotoxicity assays, natural killer (NK) cells expressing FCGR3A 158V induced more C. neoformans-infected monocyte cytotoxicity than those expressing FCGR3A 158F. Together, these results show an association between the FCGR3A 158V allele and risk for HIV-associated CD and suggest that this polymorphism could promote C. neoformans pathogenesis via increased binding of C. neoformans immune complexes, resulting in increased phagocyte cargo and/or immune activation.

Original languageEnglish (US)
Article numbere00573-13
JournalmBio
Volume4
Issue number5
DOIs
StatePublished - Aug 27 2013

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IgG Receptors
Cryptococcus neoformans
HIV
T-Lymphocytes
Alleles
Odds Ratio
CHO Cells
Mycoses
Statistical Models
Phagocytes
CD4 Lymphocyte Count
Antigen-Antibody Complex
Natural Killer Cells
Monocytes
Acquired Immunodeficiency Syndrome
Cohort Studies
Research Design
Immunoglobulin G
Genotype
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Microbiology
  • Virology

Cite this

Rohatgi, S., Gohil, S., Kuniholm, M. H., Schultz, H., Dufaud, C., Armour, K. L., ... Pirofski, L. (2013). Fc gamma receptor 3A polymorphism and risk for HIV-associated cryptococcal disease. mBio, 4(5), [e00573-13]. https://doi.org/10.1128/mBio.00573-13

Fc gamma receptor 3A polymorphism and risk for HIV-associated cryptococcal disease. / Rohatgi, Soma; Gohil, Shruti; Kuniholm, Mark H.; Schultz, Hannah; Dufaud, Chad; Armour, Kathryn L.; Badri, Sheila; Mailliard, Robbie B.; Pirofski, Liise-anne.

In: mBio, Vol. 4, No. 5, e00573-13, 27.08.2013.

Research output: Contribution to journalArticle

Rohatgi, S, Gohil, S, Kuniholm, MH, Schultz, H, Dufaud, C, Armour, KL, Badri, S, Mailliard, RB & Pirofski, L 2013, 'Fc gamma receptor 3A polymorphism and risk for HIV-associated cryptococcal disease', mBio, vol. 4, no. 5, e00573-13. https://doi.org/10.1128/mBio.00573-13
Rohatgi S, Gohil S, Kuniholm MH, Schultz H, Dufaud C, Armour KL et al. Fc gamma receptor 3A polymorphism and risk for HIV-associated cryptococcal disease. mBio. 2013 Aug 27;4(5). e00573-13. https://doi.org/10.1128/mBio.00573-13
Rohatgi, Soma ; Gohil, Shruti ; Kuniholm, Mark H. ; Schultz, Hannah ; Dufaud, Chad ; Armour, Kathryn L. ; Badri, Sheila ; Mailliard, Robbie B. ; Pirofski, Liise-anne. / Fc gamma receptor 3A polymorphism and risk for HIV-associated cryptococcal disease. In: mBio. 2013 ; Vol. 4, No. 5.
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