title: Increase of HLA-DR-positive natural killer cells in peripheral blood from patients with IgA nephropathy.
abstract: Previous in vivo and in vitro studies have presented various abnormalities of cellular immunity in patients with IgA nephropathy (IgAN). In the present study, we described increased expression of HLA-DR antigens on peripheral natural killer cells (NK cells) in relation to altered cytokine interactions. The numbers of HLA-DR expressing NK cells were enumerated by two-color flow cytometry and found to be significantly increased in patients with IgAN. Peripheral blood mononuclear cells were then fractionated into pure NK cells by a magnetic cell-sorting system and analyzed concerning expression of messages of interleukin (IL)-2, IL-4, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). Among the four cytokines, only the IFN-gamma message was significantly increased in patients' NK cells. Furthermore, intensity of the IFN-gamma message in NK cells showed positive correlation with the percentage of HLA-DR-positive NK cells from the same patient. Then we assayed serum levels of IL-2, IL-12, and IFN-gamma by enzyme-linked immunosorbent assay (ELISA) and the levels of IL-12 and IFN-gamma showed positive correlations with HLA-DR expression on NK cells. Creatinine clearance of the patients was reevaluated 36 months later, and patients with high HLA-DR on NK cells tended to show faster deterioration of renal function than patients with lower HLA-Dr expression. On the basis of these findings, we suggested that HLA-DR-positive NK cells in patients with IgAN form an "activated" population that produces IFN-gamma, and this unique cell population may be maintained by multiple factors and be involved in the development and progression of IgAN.
authors.affiliation: Department of Internal Medicine, Tokai University, School of Medicine, Kanägawa, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Yano
authors.forename: M
authors.initials: M
authors.lastname: Endoh
authors.forename: Y
authors.initials: Y
authors.lastname: Nomoto
authors.forename: H
authors.initials: H
authors.lastname: Sakai
authors.forename: A
authors.initials: A
authors.lastname: Rifai
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D001772:Blood Cell Count; D005260:Female; D005434:Flow Cytometry; D005922:Glomerulonephritis, IGA / Q000276:immunology*; D006684:HLA-DR Antigens / Q000032:analysis*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged
chemical_list: D006684:HLA-DR Antigens