Kacprzyk Feliks
Klinika Nefrologii Instytutu Medycyny Wewnetrznej UM w Łodzi.
Pol Merkur Lekarski. 2003 Oct;15(88):383-6; discussion 386-7.
In sera and urine of healthy and diseased patients two soluble types of TNF receptors--p55--sTNF RI and p75--sTNF RII have been detected. They can protect cells against excessive cytotoxic activity of TNF-alpha in vitro and in vivo. The aim of the study was to investigate the prognostic significance and role of sTNF R in various types of glomerular diseases. We studied 49 patients with primary glomerular diseases (5 minimal change--MC; 4 focal glomerulosclerosis--FSGN; 4 membranous nephropathy--MN; 12 mesangial proliferative GN--MSPGN; 18 IgA nephropathy--IgAN; and 6 membranoproliferative GN--MPGN) and 10 healthy persons. Renal biopsies were evaluated by light and immunofluorescence microscopy. STNF RI and sTNF RII concentrations were measured by ELISA (BIOSOURCE international kits). The treatment of patients consisted of 3 to 5 i.v. methylprednisolone pulses (1.0 g per single dose, average total 1.0 g/20 kg given alternate days) followed by oral prednisone 20 to 25 mg/day and six monthly i.v. cyclophosphamide 0.6 g/1 m2/month. The studied groups showed a significantly higher concentration of sTNF RI and sTNF RII in their sera and urine when compared with the control. In patient groups serum Cr showed significant correlations with volume of interstitial tissue in renal biopsy, correlation of serum Cr with serum sTNF RI, serum sTNF RI with serum sTNF RII and with urinary sTNF RI, serum sTNF RII with urinary sTNF RI and with urinary sTNF RII. The ratio of serum sTNF RI to serum sTNF RII in patients was unchanged compared to the controls but ratio of urinary sTNF RI to sTNF RII was higher in all patient groups except patients with MC. In patients with renal sufficiency (Cr < 1.3 mg/dl) and reduction of proteinuria > 50% after 1 year of therapy urinary secretion of sTNF RII was higher before treatment than in patients with protein reduction < 50%. In patients with renal insufficiency and reduction of proteinuria > 50% urinary excretion of sTNF RI was lower than in patients with lower reduction of proteinuria (< 50%) after 1 year of therapy. Our results suggest that serum sTNF R could be useful as indicator of clinical activity of the disease and urinary excretion of soluble receptors as a predictor of effectiveness of immunosuppressive therapy.
在健康和患病患者的血清及尿液中，已检测到两种可溶性肿瘤坏死因子受体——p55——可溶性肿瘤坏死因子受体I（sTNF RI）和p75——可溶性肿瘤坏死因子受体II（sTNF RII）。它们在体外和体内均可保护细胞免受肿瘤坏死因子-α（TNF-α）过度的细胞毒性作用。本研究的目的是探讨可溶性肿瘤坏死因子受体（sTNF R）在各类肾小球疾病中的预后意义及作用。我们研究了49例原发性肾小球疾病患者（5例微小病变——MC；4例局灶性肾小球硬化——FSGN；4例膜性肾病——MN；12例系膜增生性肾小球肾炎——MSPGN；18例IgA肾病——IgAN；6例膜增生性肾小球肾炎——MPGN）以及10名健康人。通过光镜和免疫荧光显微镜对肾活检组织进行评估。采用酶联免疫吸附测定法（ELISA，BIOSOURCE国际试剂盒）测定sTNF RI和sTNF RII的浓度。患者的治疗方案为静脉注射3至5次甲泼尼龙冲击治疗（单次剂量1.0 g，平均总量1.0 g/20 kg，隔日给药），随后口服泼尼松20至25 mg/天，并每6个月静脉注射环磷酰胺0.6 g/1 m²/月。与对照组相比，研究组患者血清和尿液中的sTNF RI和sTNF RII浓度显著更高。在患者组中，血清肌酐（Cr）与肾活检组织间质组织体积、血清Cr与血清sTNF RI、血清sTNF RI与血清sTNF RII及尿sTNF RI、血清sTNF RII与尿sTNF RI及尿sTNF RII之间均存在显著相关性。与对照组相比，患者血清中sTNF RI与sTNF RII的比值未发生变化，但除MC患者外，所有患者组尿中sTNF RI与sTNF RII的比值均更高。在治疗1年后，肾功能正常（Cr < 1.3 mg/dl）且蛋白尿减少> 50%的患者中，治疗前尿sTNF RII的分泌量高于蛋白尿减少< 50%的患者。在肾功能不全且蛋白尿减少> 50%的患者中，治疗1年后尿sTNF RI的排泄量低于蛋白尿减少程度较低（< 50%）的患者。我们的结果表明，血清sTNF R可作为疾病临床活动的指标，而可溶性受体的尿排泄量可作为免疫抑制治疗效果的预测指标。
