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Altered cytokine profiles in patients with Chuvash polycythemia
Author(s) -
Niu Xiaomei,
Miasnikova Galina Y.,
Sergueeva Adelina I.,
Polyakova Lydia A.,
Okhotin Daniel J.,
Tuktanov Nikolai V.,
Nouraie Mehdi,
Ammosova Tatiana,
Nekhai Sergei,
Gordeuk Victor R.
Publication year - 2009
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.21327
Subject(s) - cytokine , tumor necrosis factor alpha , endocrinology , medicine , immunology , proinflammatory cytokine , biology , interleukin , cd8 , inflammation , immune system
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)‐1α and HIF‐2α 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‐γ, granulocyte‐monocyte colony‐stimulating factor, tumor necrosis factor‐α) 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. Am. J. Hematol., 2009. © 2008 Wiley‐Liss, Inc.