NATURAL-KILLER-CELL IN IGA NEPHROPATHY

Some studies have suggested that the cytotoxicity of the natural kille r (NK) cell is inversely proportional to the expression of class I maj or histocompatibility complex (MHC) antigens on target cells. The incr eased activity of the NK eel in Igh nephropathy has been studied previ ously, however, little is known about the NK cell function in IgA neph ropathy. We examined the cytotoxicity of NK cells in IgA nephropathy a nd investigated the change in class I MHC antigen expression on K562 c ells treated with peripheral blood mononuclear cells (PBMC) culture su pernatant of patients with IgA nephropathy, and its relation to K562 c ell 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 I gA nephropathy patients had proteinuria (> 100mg/dL) and microscopic h aematuria. Their serum IgA levels in study patients were higher than t hose in healthy controls (292.2 +/- 91.8 mg/dL us 205.4 +/- 43.4 mg/dL ; P = 0.014; mean age 37 years, range 19-47 years). The cytotoxicity o f NK cells was assayed by chromium-release method. K562 cells were tre ated with PBMC culture supernatant of either patients or controls for 12 h. Part of the treated K562 cells were used to measure their suscep tibility to cytotoxicity of NK cells from the healthy volunteer and th e remainder were used to measure the MHC class I expression. Major his tocompatibility complex class I expression was assayed using FAC Scan. Cytokines such as interleukin (IL)2, IL12, interferon-gamma (IFN-gamm a), tumour necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta (TGF-beta) in serum and PBMC culture supernatant were meas ured by ELISA. The following results were obtained: (i) cytotoxic acti vity of the NK cells from IgA nephropathy on K562 cells was higher tha n that obtained from healthy controls; () 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 antig ens on K562 cells was upregulated by treatment with PBMC culture super natant; (iv) target cell susceptibility to cytotoxicity of NK cells wa s inversely proportional to the expression of class I 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-gamma (r = 0.88, P = 0.0001) and TNF-alpha (r = 0.926, P = 0.0001) in PBMC culture supernatant. However, there are no differen ces in the results (ii)-(v) between patients and healthy controls. We conclude that the serum IgA levels and NK cell cytotoxicity found in I gA nephropathy patients with proteinuria and haematuria are higher tha n those of controls. K562 cell susceptibility to cytotoxicity of activ ated NK cells is inversely proportional to the expression of class I M HC antigens; however, this phenomenon is unlikely to be specific to Ig A nephropathy. Further studies are needed in order to determine the ro le of NK cells in pathogenesis of IgA nephropathy.