Park C W, Song H C, Shin Y S, Ahn S J, Kim Y S, Kim S Y, Choi E J, Chang Y S, Bang B K
Department of Internal Medicine, The Catholic University of Korea, Seoul.
Nephron. 1998;79(1):44-9. doi: 10.1159/000044990.
In primary minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), increased lymphocyte reactivity to renal antigens has been defined. Soluble HLA class I antigen (sHLA-I) is actively secreted by T and B lymphocytes when they are stimulated by mitogens, antigens and lymphokines. To determine if serum and urine sHLA-I levels could predict steroid response in patients with MCD and differentiate those from FSGS, we have investigated 45 healthy controls, biopsy-proven 17 patients with MCD (edema and 24-hour urine protein > 3.5 g/day), 8 patients with FSGS (24-hour urine protein > 1 g/day) and 10 patients with membranous nephropathy (MGN) (24-hour urine protein > 1 g/day). Before and after prednisone therapy (1 mg/kg/day or 2 mg/kg/EOD for 8 weeks), the levels of serum and urinary sHLA-I were measured by ELISA (sHLA-STAT; Sangstat Co., Calif., USA). After 8 weeks of treatment, 10 patients with MCD were responders (MCD-CR) while the other 7 patients with MCD were nonresponders (MCD-NR). Three of 7 patients with MCD-NR were re-biopsied and finally diagnosed as FSGS. They were included in the data of patients with FSGS. In healthy controls, serum sHLA-I was detected (415 +/- 256 ng/ml), but urinary sHLA-I was not. At entry, there were no differences in age, sex, serum Cr and 24-hour urine protein among the patients with MCD-CR, MCD-NR and FSGS, but serum albumin was significantly elevated in patients with FSGS and MGN (p < 0.05). Serum sHLA-I levels were notably elevated in MCD-CR (1,040 +/- 1,066 ng/ ml), in MCD-NR (668 +/- 315 ng/ml) and in FSGS (713 +/- 790 ng/ml), but not in patients with MGN (444 +/- 86 ng/ml) when compared with controls (p < 0.05). On the other hand, urinary sHLA-I levels in MCD-NR (541 +/- 239 ng/mg Cr) and in FSGS (457 +/- 239 ng/mg Cr) were significantly higher than those in MGN (125 +/- 28 ng/mg Cr) and in MCD-CR(100 +/- 42 ng/mg Cr, p < 0.05) and these substantial differences were maintained for 8 weeks. In all patients, serum and urinary sHLA-I levels were not reduced during 8 weeks of steroid therapy. We conclude that elevated serum and urinary sHLA-I levels reflect increased cellular immune response and disease activity in patients with MCD and FSGS. In patients with MCD, urinary sHLA-I may be an easily measurable indicator of predicting steroid response, while MCD-NR with high urinary sHLA-I levels might be re-evaluated for the possibility of FSGS.
在原发性微小病变病（MCD）和局灶节段性肾小球硬化症（FSGS）中，已确定淋巴细胞对肾脏抗原的反应性增加。可溶性人类白细胞抗原I类抗原（sHLA-I）在T淋巴细胞和B淋巴细胞受到丝裂原、抗原和淋巴因子刺激时会被主动分泌。为了确定血清和尿液中的sHLA-I水平是否可以预测MCD患者的类固醇反应，并将他们与FSGS患者区分开来，我们研究了45名健康对照者、经活检证实的17例MCD患者（有水肿且24小时尿蛋白>3.5 g/天）、8例FSGS患者（24小时尿蛋白>1 g/天）和10例膜性肾病（MGN）患者（24小时尿蛋白>1 g/天）。在泼尼松治疗前和治疗后（1 mg/kg/天或2 mg/kg/隔日，共8周），采用酶联免疫吸附测定法（sHLA-STAT；美国加利福尼亚州桑斯塔特公司）检测血清和尿液中的sHLA-I水平。治疗8周后，10例MCD患者为反应者（MCD-CR），而其他7例MCD患者为无反应者（MCD-NR）。7例MCD-NR患者中的3例接受了再次活检，最终被诊断为FSGS。他们被纳入FSGS患者的数据中。在健康对照者中，检测到血清sHLA-I（415±256 ng/ml），但未检测到尿液中的sHLA-I。在入组时，MCD-CR、MCD-NR和FSGS患者在年龄、性别、血清肌酐和24小时尿蛋白方面没有差异，但FSGS和MGN患者的血清白蛋白显著升高（p<0.05）。与对照组相比，MCD-CR患者（1,040±1,066 ng/ml）、MCD-NR患者（668±315 ng/ml）和FSGS患者（713±790 ng/ml）的血清sHLA-I水平显著升高，而MGN患者（444±86 ng/ml）则未升高（p<0.05）。另一方面，MCD-NR患者（541±239 ng/mg肌酐）和FSGS患者（457±239 ng/mg肌酐）的尿液sHLA-I水平显著高于MGN患者（125±28 ng/mg肌酐）和MCD-CR患者（100±-42 ng/mg肌酐，p<0.05），并且这些显著差异持续了8周。在所有患者中，类固醇治疗8周期间血清和尿液中的sHLA-I水平均未降低。我们得出结论，血清和尿液中sHLA-I水平升高反映了MCD和FSGS患者细胞免疫反应增强和疾病活动。在MCD患者中，尿液sHLA-I可能是预测类固醇反应的一个易于测量的指标，而尿液sHLA-I水平高的MCD-NR患者可能需要重新评估是否有FSGS的可能性。
