FcγRIIa genotype predicts progression of HIV infection

Donald N. Forthal, Gary Landucci, Jay Bream, Lisa Paula Jacobson, Tran B. Phan, Benjamin Montoya

Research output: Contribution to journalArticle

Abstract

Polymorphisms in FcγR genes are associated with susceptibility to or severity of a number of autoimmune and infectious diseases. We found that HIV-infected men in the Multicenter AIDS Cohort Study with the FcγRIIa RR genotype progressed to a CD4+ cell count of 3 at a faster rate than individuals with the RH or HH genotypes (relative hazard = 1.6; p = 0.0001). However, progression to AIDS (using the broad definition of either a CD4+ cell count 3 or development of an AIDS-defining illness) was less impacted by FcγRIIa genotype, largely because HH homozygotes had an increased risk of Pneumocystis jiroveci pneumonia as an AIDS-defining illness. We also showed that chronically infected subjects develop a substantial antigp120-specific IgG2 response. Moreover, HIV-1 immune complexes are more efficiently internalized by monocytes from HH subjects compared with RR subjects, likely because of the presence of IgG2 in the complexes. Finally, the FcγRIIIa F/V gene polymorphism was not associated with progression of HIV infection, but, as demonstrated previously, did predict the risk of Kaposi's sarcoma. These results demonstrate the importance of FcγRs in AIDS pathogenesis and point toward a critical role for interactions between FcγRs and immune complexes in disease progression.

Original languageEnglish (US)
Pages (from-to)7916-7923
Number of pages8
JournalJournal of Immunology
Volume179
Issue number11
StatePublished - Dec 1 2007

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HIV Infections
Acquired Immunodeficiency Syndrome
Genotype
CD4 Lymphocyte Count
Immunoglobulin G
Immune Complex Diseases
Pneumocystis carinii
Pneumocystis Pneumonia
Kaposi's Sarcoma
Homozygote
Antigen-Antibody Complex
Genes
Autoimmune Diseases
Communicable Diseases
Disease Progression
HIV-1
Monocytes
Cohort Studies
HIV

ASJC Scopus subject areas

  • Immunology

Cite this

Forthal, D. N., Landucci, G., Bream, J., Jacobson, L. P., Phan, T. B., & Montoya, B. (2007). FcγRIIa genotype predicts progression of HIV infection. Journal of Immunology, 179(11), 7916-7923.

FcγRIIa genotype predicts progression of HIV infection. / Forthal, Donald N.; Landucci, Gary; Bream, Jay; Jacobson, Lisa Paula; Phan, Tran B.; Montoya, Benjamin.

In: Journal of Immunology, Vol. 179, No. 11, 01.12.2007, p. 7916-7923.

Research output: Contribution to journalArticle

Forthal, DN, Landucci, G, Bream, J, Jacobson, LP, Phan, TB & Montoya, B 2007, 'FcγRIIa genotype predicts progression of HIV infection', Journal of Immunology, vol. 179, no. 11, pp. 7916-7923.
Forthal DN, Landucci G, Bream J, Jacobson LP, Phan TB, Montoya B. FcγRIIa genotype predicts progression of HIV infection. Journal of Immunology. 2007 Dec 1;179(11):7916-7923.
Forthal, Donald N. ; Landucci, Gary ; Bream, Jay ; Jacobson, Lisa Paula ; Phan, Tran B. ; Montoya, Benjamin. / FcγRIIa genotype predicts progression of HIV infection. In: Journal of Immunology. 2007 ; Vol. 179, No. 11. pp. 7916-7923.
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