Natural killer cell in IgA nephropathy
Authors: KIM Myung‐Jae , HONG Seong‐Pyo , LEE Tae‐Won , IHM Chin‐Gyoo 
Published: April 2007

Summary: Some studies have suggested that the cytotoxicity of the natural killer (NK) cell is inversely proportional to the expression of class I major histocompatibility complex (MHC) antigens on target cells. the increased activity of the NK cell in IgA nephropathy has been studied previously, however, little is known about the NK cell function in IgA nephropathy. We examined the cytotoxicity of NK cells in IgA nephropathy and investigated the change in class I MHC antigen expression on K562 cells treated with peripheral blood mononuclear cells (PBMC) culture supernatant of patients with IgA nephropathy, and its relation to K562 cell susceptibility to cytotoxicity of NK cells obtained from a normal healthy volunteer. We studied 10 IgA nephropathy patients (three males, seven females) and 10 age and sex matched healthy controls. the 10 IgA nephropathy patients had proteinuria (<100mg/dL) and microscopic haematuria. Their serum IgA levels in study patients were higher than those in healthy controls (292.2 ± 91.8 mg/dL vs 205.4 ± 43.4 mg/dL; P=0.014; mean age 37 years, range 19‐47 years). the cytotoxicity of NK cells was assayed by chromium‐release method. K562 cells were treated with PBMC culture supernatant of either patients or controls for 72 h. Part of the treated K562 cells were used to measure their susceptibility to cytotoxicity of NK cells from the healthy volunteer and the remainder were used to measure the MHC class I expression. Major histocompatibility complex class I expression was assayed using FAC Scan. Cytokines such as interleukin (IL)2, IL12, interferon‐γ (IFN‐γ), tumour necrosis factor‐α (TNF‐α), and transforming growth factor‐β (TGF‐β) in serum and PBMC culture supernatant were measured by ELISA. the following results were obtained: (i) cytotoxic activity of the NK cells from IgA nephropathy on K562 cells was higher than that obtained from healthy controls; (ii) pre‐treatment of K562 cells with PBMC culture supernatant resulted in decreased susceptibility to lysis of activated NK cells; (iii) the expression of class I MHC antigens on K562 cells was upregulated by treatment with PBMC culture supernatant; (iv) target cell susceptibility to cytotoxicity of NK cells was inversely proportional to the expression of class 1 MHC antigens (r = ‐0.71, P= 0.002); and (v) the expression of class I MHC antigens on K562 cells treated with PBMC culture supernatant correlated with the levels of IFN‐γ (r = 0.88, P= 0.0001) and TNF‐α (r = 0.926, P= 0.0001) in PBMC culture supernatant. However, there are no differences in the results (ii)‐(v) between patients and healthy controls. We conclude that the serum IgA levels and NK cell cytotoxicity found in IgA nephropathy patients with proteinuria and haematuria are higher than those of controls. K562 cell susceptibility to cytotoxicity of activated NK cells is inversely proportional to the expression of class I MHC antigens; however, this phenomenon is unlikely to be specific to IgA nephropathy. Further studies are needed in order to determine the role of NK cells in pathogenesis of IgA nephropathy.