Altered cytokine profiles in patients with Chuvash polycythemia.

Autor: Niu X; Center for Sickle Cell Disease and Department of Medicine, Howard University, Washington, District of Columbia 20060, USA., Miasnikova GY, Sergueeva AI, Polyakova LA, Okhotin DJ, Tuktanov NV, Nouraie M, Ammosova T, Nekhai S, Gordeuk VR
Jazyk: angličtina
Zdroj: American journal of hematology [Am J Hematol] 2009 Feb; Vol. 84 (2), pp. 74-8.
DOI: 10.1002/ajh.21327
Abstrakt: Chuvash polycythemia results from a homozygous 598C>T mutation in exon 3 of the von Hippel-Lindau (VHL) gene. This disrupts the normoxia pathway for degrading hypoxia inducible factor (HIF)-1alpha and HIF-2alpha causing altered expression of HIF-1 and HIF-2 inducible genes. As hypoxia induces expression of pro-inflammatory cytokines, we hypothesized that there might be an elevation of Th1 cytokines in the setting of Chuvash polycythemia. We analyzed plasma concentrations of Th1 (interleukins-2 and 12, interferon-gamma, granulocyte-monocyte colony-stimulating factor, tumor necrosis factor-alpha) and Th2 cytokines (interleukins-4, 5, 10, and 13) using the Bio-Plex multiplex suspension array system in 34 VHL598C>T homozygotes and 32 VHL wild-type participants from Chuvashia. Concentrations of all the Th1 and Th2 cytokines measured were elevated in the VHL598C>T homozygotes compared with the control wild-type participants, but the ratios of Th1 to Th2 cytokines did not differ by genotype. In parallel, peripheral blood concentrations of CD4 positive T-helper cells and CD4/CD8 ratio were lower in the VHL598C>T homozygotes. In conclusion, the up-regulated hypoxic response in Chuvash polycythemia is associated with increased plasma products of both the Th1 and Th2 pathways, but the balance between the two pathways seems to be preserved.
Databáze: MEDLINE