血脂水平与IgA肾病患者临床病理特征及C3、C4水平的关系

目的 探讨血脂水平与IgA肾病（IgAN）患者临床病理特征及补体3、4（C3、C4）水平的关系。方法 选取2018年1月—2021年12月在蚌埠医学院第一、二附属医院肾脏内科行肾活检诊断为IgAN的119例患者为研究对象,根据血脂水平将其分为异常组（84例）［甘油三酯（TG）≥ 2.26 mmol/L和/或总胆固醇（TC）≥ 6.22 mmol/L和/或高密度脂蛋白（HDL）< 1.04 mmol/L］、正常组（35例）,比较两组患者临床病理特征,采用Pearson法分析血脂（TG、TC、HDL）与C3、C4水平的相关性。结果 异常组与正常组患者年龄、性别构成、收缩压、舒张压、血红蛋白、白蛋白、血肌酐、eGFR、血尿素氮、血尿酸、24 h尿蛋白、尿红细胞计数、CKD分期、肾小球球性硬化、肾小管萎缩面积、小球新月体、间质血管损伤程度、炎症细胞浸润及Lee氏分级比较,差异均无统计学意义（P >0.05）。异常组BMI、C3、C4水平高于正常组（P <0.05）。IgAN患者血清TG与C4呈正相关（r =0.247,P <0.05）,与C3无相关性（r =0.102,P >0.05）;血清TC与C4呈正相关（r =0.240,P <0.05）,与C3无相关性（r =0.029,P >0.05）;血清HDL与C3、C4无相关性（r =0.080和0.171,均P >0.05）。结论 部分IgAN患者存在血脂水平异常,且其血清TG、TC与C4水平呈正相关。     

A screening programme for microalbuminuria at a diabetes clinic in Apulia,southern Italy

Microalbuminuria is a predictor of renal and cardiovascular disease in both type 1 (insulin-dependent) and type 2 (insulin-independent) diabetes. We report on a screening programme for microalbuminuria at a diabetes clinic in Italy. All diabetic patients without Albustix-positive proteinuria attending the clinic between April and September 1991 were screened. Microalbuminuria was defined as a urinary albumin/creatinine ratio, on an early morning sterile urine sample, >3 in at least two consecutive urine collections. Three hundred and fifty patients, 45 (20 female, 25 female) type 1 and 305 (145 male, 160 female) type 2 diabetics, were examined. The age range was 18–42 years and 36–73 years and duration of diabetes 1–24 and 1–35 years for type 1 and type 2 diabetic patients respectively. Blood pressure, lipids, glycosylated haemoglobin, body mass index and insulin dose, where appropriate, were measured in all patients. Microalbuminuria was found in 8 (22%) of the type 1 diabetics. These patients had a longer duration of diabetes (17.5 vs 7.4 years,P<0.001), higher diastolic blood pressure (86±2.1 vs 76±2.6 mmHg,P<0.05) and an increased total serum cholesterol level (203±23 vs 180±25 mg/dl,P<0.05) compared with diabetic patients with microalbuminuria. Of the type 2 diabetic patients 95 (33%) were found to have microalbuminuria and 210 (69%) nor-moalbumiuria. The prevalence of hypertension (defined blood pressure >140/90 mmHg or antihypertensive treatment) and of dyslipidaemia (defined as total cholesterol >200 and triglycerides >170 or hypolipidaemic treatment) were significantly higher (P<0.001 and 0.01 respectively) in patients with microalbuminuria. This study shows a prevalence of microalbuminuria in type 1 and type 2 diabetic patients similar to that reported in surveys of diabetes clinic outpatients in northern Europe. The association between microalbuminuria and recognized risk factors for cardiovascular and renal disease justifies screening programmes for microalbuminuria for early detection of at-risk diabetic patients and for the implementation of preventive therapeutic measures.     

Dietary factors and progression of diabetic nephropathy

The role of dietary factors in patients with type 1 (insulin-dependent) diabetes is reviewed by examining three different aspects: the effect of an acute protein load, the effect of dietary protein restriction on the progression of nephropathy and the metabolic effects of low-protein diets. After an acute protein load some impairment of the renal functional reserve may be observed only in patients with type 1 diabetes and overt nephropathy. However, the renal functional reserve is not able to give useful indications of the extent of renal damage and the prognosis of the disease. Both short-term and long-term dietary protein restriction are followed by a significant decrease in glomerular filtration rate (GFR) and albuminuria in type 1 diabetics with incipient nephropathy. In patients with overt nephropathy the long-term administration of a low-protein diet is followed by significant reductions in the rate of decline of GFR and in urinary protein excretion only when started at GFR values higher than 45 ml/min. The rate of functional deterioration when dietary treatment is prescribed seems critical in modulating the effects of a low-protein diet. In addition, low-protein diets may exert important metabolic and clinical effects beyond their supposed effect on progression. Clearly, an adequate dietary regimen is only part of the medical treatment in patients with diabetic nephropathy.     

Detection of IgA protease from Haemophilus influenzae by immunoblotting

IgA protease produced by various strains of Haemophilus infuenzae can digest serum IgA and yield its fragments which can react with anti-IgA serum. We assayed IgA protease activity by detecting the digests of IgA by SDS-PAGE and immunoblotting. The digests were separated with SDS-PAGE, transferrend to nitrocellulose membranes and detected with anti- ( chain of human IgA, its Fab and its Fc) immunoglobulin conjugated peroxidases.Using this method, we can determine which type of IgA protease is produced by various of H. infuenzae strains. All the 20 strains isolated from respiratory tracts produced IgA protease.     

Alpha-SM actin expression as prognostic indicator in IgA nephropathy (Berger's disease)

Recent studies have demonstrated that α-Smooth Muscle actin expression in glomerular and tubulointerstitial compartments of renal tissue could represent a prognostic marker in several renal diseases. Our objective was to identify the prognostic value of α-SM actin actin expression on the evolution of renal damage in Primary IgA nephropathy (Berger’s Disease). 43 patients followed up from 1988 to 1999 at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil, was studied. Clinical-laboratory data were obtained from the medical records of the patients using a protocol containing name, race, gender, origin, profession, age at clinical presentation of the disease and personal and family history. The parameters assessed in the approach to IgA nephropathy were serum creatinine, creatinine clearance, serum albumin, total serum protein, 24 hours proteinuria, glycaemia, serum sodium, potassium, calcium and phosphorus ions, analysis of urinary sediment, serum complement profile, blood count, and renal biopsy. Morphological evaluation was performed by renal biopsy using common light and immunofluorescence microscopy. Immunohistochemical studies were performed using a murine monoclonal antibody to α-SM actin. Our data showed that α-SM actin expression in the glomerular and tubulointerstitial compartments are not correlated with unfavorable clinical course of primary IgA nephropathy.     

2型糖尿病患者血IL-6与循环内皮细胞的关系及意义

目的探讨2型糖尿病(DM)患者血管内皮细胞损伤与血白介素6(IL-6)的关系及其意义。方法检测45例2型DM患者及20例正常人外周血IL-6和循环内皮细胞(CEC)水平并进行比较。结果①2型DM患者血IL-6和CEC水平高于正常人(P<0.05);②早期糖尿病肾病患者血CEC水平明显高于单纯糖尿病患者(P<0.01);③多元逐步回归分析显示CEC与血IL-6水平和尿蛋白排泄率(UAER)显著相关,标准偏回归系数β分别为0.264(P=0.033)和0.545(P=0.000)。结论2型糖尿病血管内皮细胞损伤与体内IL-6升高有密切关系,并在糖尿病肾病的发病过程中起一定作用。     

IL-10-driven immunoglobulin production by B lymphocytes from IgA-deficient individuals correlates to infection proneness

In search for a possible explanation of the phenotypic heterogeneity in IgA deficiency, we studied the function of B cells from IgA-deficient (IgAd) individuals. Two groups of IgAd individuals, one frequently infected and one clinically apparently healthy, as well as normal controls, were studied. Peripheral blood mononuclear cells (PBMC) and B cells from IgAd individuals and controls were cultured with Staphylococcus aureus Cowan I strain and with anti-CD40 MoAb presented on the CD32-transfected fibroblast cell line in the presence of IL-10. In this experimental system PBMC and B cells from the infection-prone IgAd individuals produced only minute amounts of IgA. In contrast, PBMC and B cells from healthy IgAd subjects secreted significantly more IgA1 and IgA2 in comparison with infection-prone IgAd patients (P < 0.05). These data suggest that the abnormalities of B cell differentiation in IgAd could be of heterogeneous origin. Thus, whereas in healthy IgAd subjects IgA production may be efficiently up-regulated in vitro by addition of IL-10 to CD40-activated B cell culture, the corresponding B cell differentiation does not occur in infection-prone IgAd patients. These observations provide a conceptual framework for phenotypic heterogeneity in IgAd subjects.     

Etiology of IgA nephropathy syndrome

Since Berger's original paper on mesangial IgA-IgG deposition with hematuria, there have been a number of clinical and pathological studies regarding IgA immune complexes, the mechanisms of glomerular IgA deposition leading to glomerular injury and animal models of IgA nephropathy. During the last quarter of this century, glomerular changes such as IgA nephropathy have also been observed in cases associated with other diseases, such as systemic lupus erythematosus, Schoenlein-Henoch purpura, liver cirrhosis and chronic inflammatory diseases of the lung. This evidence supports the idea of an IgA nephropathy syndrome. On the other hand, IgA is thought to be an important humoral factor at the mucosal immune system and appears to have an antibody function against various etiologic candidates of extrinsic or intrinsic substances at the mucosal and systemic immune system. Glomerular IgA deposition in IgA nephropathy syndrome is thought to result from elevated levels of circulating immune complexes or aggregated IgA due to an overproduction of polymeric IgA as antibodies in the serum and due to the clearance impairment of IgA immune complexes in the hepatic and splenic phagocytic system. The glomerular IgA subclass is not one-sided, but should be evaluated in comparison with the age of patients at renal biopsy; this indicates the approximate age of onset. Cirrhotic IgA glomerulonephritis is not related to Hepatitis B or C virus infection, but to the pathophysiologic condition of liver cirrhosis. Various etiologic candidates such as viral, microbial, dietary antigens or auto-antigens have been listed and experimental models of IgA nephropathy syndrome have provided some clues in understanding the etiology of primary IgA nephropathy. However much still remains to be clarified and some specific epitopes common among these etiologic candidates will have to be identified.     

Role of Der p 1–specific B cells in immune tolerance during 2 years of house dust mite–specific immunotherapy

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