Abstracts (complete list) - Wissenschaft Online

Maren Mönkemeyer, Hans Heiken, Rachel Thomas, Reinhold E. Schmidt, Torsten Witte
Higher risk of CMV reactivation in HIV-1 infected patients
homozygous for MICA5.1
Background:
Infection with human cytomegalovirus (CMV) induces surface expression of MHC class I
chain-related A (MICA), a ligand for the activating receptor NKG2D. This leads to
improved recognition and elimination of infected cells by NK cells as well as CD8+ T
cells. The MICA allele MICA5.1 codes for a truncated, dysfunctional protein.
The aim of this study was to investigate the contribution of genetic ability to express
functional MICA protein on the susceptibility to severe CMV reactivation in
immunocompromised individuals. HCV and GBV-C coinfected HIV-1 infected patients
were analysed as controls.
Methods:
The frequency of the MICA5.1 allele was assessed in 230 Caucasian HIV-1 infected
patients as well as in 29 healthy controls. MICA5.1 allele was analysed by PCR. The
association of MICA5.1 homozygosity and risk of CMV reactivation was calculated by
Pearson Chi-Square.
Results:
Comparison of patients with and without a history of CMV disease manifestation
revealed an enhanced susceptibility to reactivation of CMV for HIV-1 infected patients,
homozygous for MICA5.1. The percentage of homozygous MICA5.1 individuals was
similar in HIV-1 infected patients and healthy controls. In contrast, no evidence was
found for a correlation between a homozygous MICA5.1 genotype and an increased risk
of infection with GBV-C or HCV.
Conclusions:
This study is the first to evaluate in vivo the impact of a MICA polymorphism on risk of
viral infections. A significant correlation between homozygous MICA5.1 genotype and
susceptibility to CMV, but not to GBV-C or HCV coinfection, in immunocompromised
individuals was demonstrated. The elimination of infected cells via NKG2D-expressing
NK and T cells appears to be a more important immune reaction in CMV than HIV-1,
GBV-C or HCV infection.
Supported by BMBF KN Rheuma C2.12