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. 2002 Sep 15;186(6):843-6.
doi: 10.1086/342413. Epub 2002 Aug 16.

Human leukocyte antigen-B8-DR3 is a more important risk factor for severe Puumala hantavirus infection than the tumor necrosis factor-alpha(-308) G/A polymorphism

Satu Mäkelä  1 , Jukka Mustonen, Ilpo Ala-Houhala, Mikko Hurme, Jukka Partanen, Olli Vapalahti, Antti Vaheri, Amos Pasternack
Affiliations

Human leukocyte antigen-B8-DR3 is a more important risk factor for severe Puumala hantavirus infection than the tumor necrosis factor-alpha(-308) G/A polymorphism

Satu Mäkelä et al. J Infect Dis. .

Abstract

The tumor necrosis factor (TNF)-alpha(-308) G/A polymorphism (TNF-2) is in linkage disequilibrium with the human leukocyte antigen (HLA)-B8-DR3 haplotype. Both factors have been associated with severe Puumala hantavirus-induced nephropathia epidemica (NE). To examine which part of this extended haplotype might show the strongest association with the outcome of NE, the HLA-B, HLA-DRB1, and TNF-alpha(-308) alleles in 116 hospital-treated patients with NE were analyzed. The findings pointing to clinically severe NE were strongly associated with HLA-B8-DR3 haplotype. There was a trend toward severe disease in persons positive for TNF-2. This was probably due to strong linkage disequilibrium with HLA-B8-DR3, since there were no differences in the clinical severity of NE when TNF-2-positive/B8-DR3-negative persons were compared with TNF-2-negative/B8-DR3-negative persons. It is concluded that the HLA-B8-DR3 haplotype is an important contributor to the course of NE. The data indicate that the TNF-2 allele is not an independent risk factor for severe NE but a passive component in the extended haplotype.

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