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The Role Of TNF-α And Underglycosylation Of IgA1 In Mesangial Deposition In The Pathogenesis Of Patients With IgA Nephropathy

Posted on:2005-07-23Degree:MasterType:Thesis
Country:ChinaCandidate:L L XingFull Text:PDF
GTID:2144360125458306Subject:Internal Medicine
Abstract/Summary:
Object: IgA nephropathy (IgAN) is now considered the most common from of primary glomerulonephritis worldwide and a mesangial proliferative glomerulonephritis in which IgA predominantly deposits in glomerular mesangium, but the pathogenesis mechanism of IgA nephropathy is poorly understood yet. At present, many speacialists pay more and more attention to the role of TNF-α. Our study aims to investigate the role of TNF-α in the clinic and pathology as well as disease progress in IgA nephropathy ;to examine if there is a direct correlation between underglycosylation of IgA1 in mesangial deposition and the production of TNF-α. Method: The subject included 50 initial patients with primary IgA nephropathy,10 patients with minimal change nephrotic syndrome and 10 healthy people as control group;in addition to remission group to know the role of TNF-α in proteinuria. After drawing blood and collecting urine on the morning of the day when was performed the biopsy we had measured TNF-α in serum and urine of by radioimmunoassay,as well as urine creatinine so as to exclude the effect of urine flow rate; underglycosylation of IgA1 in mesangial deposition was detected from frozen sections by lectin-linked direct immunofluorescent staining ; Immunoperoxidase staining was perfomed to determine the present of TNF-α in renal tissues ,then calculated the of positive area ratio by the pathologic picture analysis.Result:Although the level of urine protein of patients with IgA nephropathy was significantly lower than that of patients with MCNS,the levels of both serum TNF-α and urine TNF-α/Cr were significantly higher compared with those of MCNS and healthy people and had an significant positive correlation with the degree of proteinuria (r=0.88,0.38 respectively,p<0.05) while serum TNF-α had no significant correlation with urine TNF-α/Cr ;the levels of serum TNF-α and urine TNF-α/Cr of patients with MCNS were higher compared with healthy people ,but was not statistically significant.Among 10 patients with IgA nephropathy who were administrated regular therpy—oral prednisone 0.8~1.0mg/kg/d plus immunosuppressive when urine protein >1g/24h and weak pathologic features and/or segmental capillary necrosis ;oral ACEI/ARⅡ and dipyridamole when urine protein <1g/24h and/or weak pathologic features—for half of year,complete remission occurred in 5 case ,the other case turned out to part remission with proteinuria reduction >50%; the levels of serum TNF-α and urine TNF-α/Cr were significantly reduced after therapy. The level of urine TNF-α/Cr with IgAN having macroscopic hematuria was significantly higher than that with microscopic hematuria ,but comparing the levels of serum TNF-α of two groups patients had no statistical significance. The numbers of weak,moderate and sever renal damage groups are 17, 17 and 16 case, comparing the levels of serum TNF-α and urine TNF-α/Cr among three groups had apparent statistical significance. Direct immunofluorescence staning revealed that among all 50 IgAN patients 22 case was positive,compared with the negative patients , the levels of serum TNF-α and urine TNF-α/Cr had no statistical significance.Immunoperoxidase staining suggested that among 50 IgA nephropathy patients ,37 case were positive, including 8 case in weak renal damage, 14 case in moderate renal damage, 15 case in sever renal damage, TNF-α was mainly localized cytoplasm of the proximal renal tubular epithelial cell ,particularly obvious in atrophu proximal tubular ;additionally observed in the interstitium and obviously located where more monocyte-macrophages infiltrated ;the glomerulis from all frozen setions were not labled with TNF-α,and that frozen setions from 10 mininal change disease patients were not labled with TNF-α,either. The serverer renal pathologic feactures was ,the higher the positive area ratio of TNF-α in renal tissues and urine TNF-α/Cr were,serum TNF-α also proportionally increased ,but not so obvious as the former two ;the positive area ratio of TNF-α had a more significa...
Keywords/Search Tags:IgA nephropathy, TNF-α, underglycosylation of IgA1, renal pathology, proteinuria
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