Humoral immunity to streptococcal antigen in acute and chronic glomerulonephritis

A study was carried out to verify the clinical usefulness of the elaborated method for the measurement of antistreptococcal antibody in revealing the streptococcal etiology of glomerulonephritis.In 158 patients with glomerulonephritis antistreptococcal antibody (ASA), circulating immune complexes (CIC) and haemolytic activity of the complement were measured.On the basis of immune complex formation it has been concluded that streptococcal infection may cause glomerulonephritis. Serial determinations of ASA and CIC are helpful in establishing the streptococcal etiology of glomerulonephritis and in monitoring the course of the disease.     

Studies on circulating immune complexes. I: Circulating immune complexes in various types of glomerulonephritis and collagen disease: a comparative study employing conglutinin solid phase radioimmunoassay and raji cell radioimmunoassay

A study was undertaken to examine the differences in serum levels of circulating immune complexes (CIC) detected by different methods in various types of collagen disease and primary glomerulonephritis. The subjects used were 16 patients with SLE, 22 with IgA nephropathy, 8 with membranoproliferative glomerulonephritis, 8 with membranous nephropathy, 6 with minimal change nephrotic syndrome, and 2 each with RA, PSS, DM, Sj?gren syndrome, PN, MCTD and overlap syndrome, respectively. CIC were measured by two assays, namely, bovine conglutinin solid phase radioimmunoassay (C-assay) and Raji cell radioimmunoassay (R-assay). In SLE, the incidence and amounts of CIC detected were higher in R-assay than in C-assay. Similar results were obtained for the other types of collagen diseases. Furthermore, a discrepancy in the incidence of CIC detected by the two assays was found in 30% of patients with collagen diseases. Concerning the detection of CIC in primary glomerulonephritis, the sensitivity of C-assay was higher than that of R-assay. This discrepancy appears to reflect the different sensitivities of the two assays. No significant correlation was found between the CIC level and the intensity of IgG deposits in various types of glomerulonephritis. These results suggest that the R-assay was better for the detection of CIC in collagen diseases, and that the C-assay was suitable for that in primary glomerulonephritis.     

Improvement of immune-complex nephritis associated with hepatitis B surface antigen excess

A case of hypocomplementemic membranoproliferative glomerulonephritis was studied during remission of nephrosis induced by high doses of corticosteroids. Hepatitis B surface antigen (HBsAg) and immune complexes were detected in serum and glomeruli. Anti-hepatitis-B surface antibody, undetectable in serum by conventional radioimmunoassays was identified in circulating immune complexes (CIC). On two occasions, improvement in renal function coincided paradoxically with an extreme increase in serum HBsAg levels as well as with marked elevation of CIC. We suggest that, as previously observed in animal models of glomerulonephritis, extreme antigen excess may inhibit glomerular deposition of immune complexes.     

Incidence of circulating immune complexes in patients with acute poststreptococcal glomerulonephritis and in patients with streptococcal impetigo

In an attempt to further study the possible contribution of circulating immune complexes (CIC) in the pathogenesis of acute poststreptococcal glomerulonephritis, 61 patients with APSGN were studied during the first three weeks of the disease, and 13 patients with noncomplicated streptococcal impetigo as a control group. C1q solid phase ELISA and Conglutinin (K) solid phase ELISA were used to measure the levels of immune complexes. The incidence of CIC in a single serum sample from patients with APSGN was 48%. Elevated levels of immune complexes were found in 46% of the patients with streptococcal impetigo. The absolute levels of CIC were comparable in both groups of patients. No correlation was found among the presence of CIC and the clinical, immunoserological or pathological findings of the disease. Our results do not support the hypothesis that trapping of the circulating immune complexes play an important role on the renal injury poststreptococcal infection. Instead, we suggest that CIC are an epiphenomena present in APSGN, and may represent rather a systemic inflammatory immune response in patients with group A streptococcal infection.     

人参对家兔系膜增生性肾小球肾炎模型循环免疫复合物的影响

目的：观察人参对家兔系膜增生性肾小球肾炎模型循环免疫复合物（CIC）的影响。方法：制成家兔系膜增生性肾小球肾炎模型,将该模型分成对照组、全剂量泼尼松组、半剂量泼尼松组、人参合用半剂量泼尼松组及单用人参组,分组给药,观察用药前后家兔血清循环免疫复合物水平的变化。结果：模型兔肾功能基本正常,但24 h尿蛋白较正常组显著升高,肾脏组织学提示系膜增生明显（以基质增生为主）,足突融合明显;人参可使模型家兔血清循环免疫复合物下降至基本正常水平,而血清免疫球蛋白水平仍保持正常;虽然全剂量和半剂量泼尼松组较模型后组、对照组血清CIC的水平下降,但血清IgG水平亦同时下降,降低其免疫功能。结论：人参在使家兔系膜增生性肾小球肾炎模型血清循环免疫复合物下降的同时,不降低其正常的免疫功能。     

Analysis of IgG immune complexes in sera from patients with membranous nephropathy: role of IgG4 subclass and low-avidity antibodies

The levels of circulating immune complexes (CIC) were determined using an anti-C3d binding assay in patients with various types of glomerulonephritis (GN). It was found that IgG class CIC were positive in 20% (7/35) of patients with idiopathic membranous nephropathy (MN) and in 80% (8/10) of patients with lupus glomerulonephritis (LN). Of these patients, IgG4 subclass CIC were observed more frequently in 29% of MN and 60% (3/5) of minimum change nephrotic syndrome, and, with less amounts, in 10% (1/10) of membranoproliferative GN (MPGN) and 20% (2/10) of IgA nephropathy. On the other hand, the patients with LN showed a lower positivity (30%) of IgG4-CIC as compared with that of IgG-CIC. In the comparison of mean levels, only MN patients showed significantly higher value than normal individuals (p less than 0.05). In patients with MN, the CIC of the other IgG subclasses (IgG1, IgG2, IgG3) were not significantly elevated and their positivities were low (9-11%). The study on the salt-dependent dissociability of CIC, which is considered to reflect the avidity of antibodies in CIC, showed that the IgG-CIC of 11 of 15 patients with MN were dissociable to various extents even at the physiological concentration. These findings suggested that IgG4 subclass specificity and low avidity may be pathogenic characteristics of IgG-CIC in certain populations of patients with MN.     

Protective role of BCG in the rabbit model of mesangial proliferative glomerulonephritis

A study was designed to investigate whether BCG could play a protective role in a rabbit model of mesangial proliferative glomerulonephritis. Fifteen rabbits were immunised with multiple injections of bovine serum albumin and their mononuclear phagocytic system was depressed by endotoxin from E. coli. The rabbits were divided into two groups: Group 1 (n = 7) received intravenous BCG from 3 weeks prior to the pathogenic immunisation and until the end of this period; Group 2 (n = 8) acted as a control and received normal saline. In the BCG group circulating immune complex (CIC) titres were significantly reduced, rabbit IgG deposition in glomeruli was significantly less, and mean glomerular cell counts were significantly less than those in the control group. We conclude that BCG stimulates the mononuclear phagocytic system to remove CIC and reduce the deposition of immune complexes in glomeruli, thereby mitigating the inflammatory response.     

Circulating immune complexes in glomerulonephritis: a longitudinal study

A longitudinal study of circulating immune complexes (CIC) was performed in 121 patients with biopsy verified glomerulonephritis (GN). 1286 blood samples were obtained during a mean observation period of 21 months. Two methods for detection of CIC were used, the Clq-binding activity and a PEG precipitation test. CIC were detected by both tests in 21% of all blood samples and detected in at least one blood sample from 57 patients. The presence of CIC was found to be either transient (34 patients), intermittent (11 patients) or permanent (12 patients). CIC were found transiently at the time of renal biopsy and disappeared within months in patients with idiopathic extracapillary GN (7 of 9 patients), endocapillary GN (2/2) and GN associated with polyarteritis nodosa (5/6), Wegener's granulomatosis (3/3) and Henoch-Schoenlein syndrome (3/6). CIC were detected either transiently, intermittently or permanently for years after renal biopsy in patients with SLE (12/14) and membranoproliferative GN type I (7/12). CIC were only occasionally detected in patients with minor change nephropathy (1/9), membranoproliferative GN type II (0/2), IgA nephropathy (6/17), focal segmental sclerosis (1/8) and membranous GN (2/11). In these patients CIC were often transiently present without apparent relationship to time since renal biopsy. Overall, a relationship was found between the presence of CIC and decreasing serum creatinine, but there was no correlation with changes in proteinuria or with increasing blood pressure. Serial measurements of CIC showed correlations with clinical events only in individual patients, but not in the population as a whole.     

Circulating immune complexes in membranoproliferative glomerulonephritis

Circulating immune complexes (CIC), measured by the solid-phase Clq method, were found to be in abnormal concentration in about half of 39 patients with membranoproliferative glomerulonephritis (MPGN). In contrast, they were present, usually in higher concentration, in nearly all patients with active lupus nephritis. Correlations between clinical course and CIC levels in patients with MPGN showed that complexes were always present when the disease was mild or "silent," but when renal impairment developed or was incipient, complexes were nearly always absent. In patients with disease of intermediate severity, characterized by definite proteinuria but without renal impairment, 50% had complexes. The presence of complexes when glomerular abnormality is relatively slight could be interpreted as indicating that the complexes measured were not nephritogenic, or that they program subsequent events that augment glomerular injury in the absence of complexes. The measurement of CIC in MPGN appears to have minimal value both in diagnosis and in determining prognosis.     

Chronic interstitial cystitis and systemic lupus erythematosus in an 8-year-old girl

An 8-year-old girl with systemic lupus erythematosus (SLE) and diffuse proliferative glomerulonephritis had chronic interstitial cystitis (CIC) early in the course of SLE. The early occurrence of CIC, the lack of intestinal symptoms, the association with vesicoureteric reflux, and the improvement of CIC during therapy with cyclosporin A were the prominent features of the patient reported here. Received June 16, 1997; received in revised form September 18, 1997; accepted September 24, 1997     

Renal Complications of Infected Ventriculoatrial Shunts

Abstract: Contamination of a ventriculoatrial shunt (VAS) with skin organisms that are usually nonpathogenic may be followed by an immunologically mediated renal injury. The bacteria characteristically involved are coagulase-negative Staphylococci (e.g., Staphylococcus epidermidis ), which strongly adhere to the plastic surface of the VAS. These bacteria are protected from the body's natural defense mechanisms and respond only poorly to antibiotics. As a result, their growth persists and produces a continuous antigenic stimulation. Circulating immune complexes (CIC) are an appropriate tool to screen for chronically infected VASs. We followed CIC in 138 VAS patients. An infected VAS was seen in 20 of the 24 patients with highly elevated CIC and in 1 of the 19 patients with moderately elevated CIC, but none of the 95 patients with normal CIC had evidence of shunt infection. Of the 21 patients with shunt infections, 8 had renal involvement (4 requiring dialysis, and 4 with proteinuria, hematuria, and/or elevated creatinine). Results from kidney biopsy specimens available from 4 patients confirmed glomerulonephritis. Of the 4 patients requiring dialysis at diagnosis, renal function recovered sufficiently to stop dialysis after successful VAS exchange in all but 1. In the other 4 patients, renal symptoms (proteinuria, creatinine) also improved after VAS revision. Chronic infection with S. epidermidis or other bacteria is a continuing problem in patients with VASs and can lead to an immune-mediated renal injury. However, the prognosis for reversal of the renal injury is relatively good if the VAS infection is treated promptly.     

乌鲁木齐市229例中老年寻常型银屑病患者骨代谢测定结果分析

目的探讨寻常型银屑病患者骨代谢结果的差异及影响因素。方法将229例已明确诊断的寻常型银屑病患者作为研究组,同时根据年龄、性别不同选择同期在我院体检中心进行体检的非银屑病健康体检者229例作为对照组。结果男性血清Ca、P银屑病组低于非银屑病组,Mg、ALP、TG、LDL-C男性、女性银屑病组均高于非银屑病组;银屑病组血清25-OH-D3高于非银屑病组;腰椎骨密度男性、女性非银屑病组均略高于银屑病组,男性银屑病组L_1、L_2及腰椎骨密度均值低于女性银屑病组,腰椎均值具有统计学差异;银屑病组右侧股骨颈及ward’s三角区骨密度略高于左侧;银屑病组患者按不同病程统计银屑病患者出现骨量减低及骨质疏松症大多发生于病程10~15年及5~10年组(分别占28.319%和27.876%),其次是15~20年组(占22.566%);分组统计男性组骨密度正常比例明显高于女性组(女性组占8.850%,男性组38.496%);同组内比较:男性发生骨量减低及骨质疏松症或骨折的比例占44.585%,而女性组占72.222%,明显高于男性组;女性组15~20年组及大于20年组出现骨折,共2例骨折(占2.778%),男性大于20年组出现1例骨折(占0.637%)。结论银屑病患者组骨代谢水平明显低于正常对照组,且在银屑病发病的早期即应该开始骨质疏松的预防教育。     

Angiotensin-converting enzyme inhibition in experimental in-situ immune complex glomerulonephritis: influence on renal function, proteinuria, and morphology

BACKGROUND: Converting enzyme inhibition (CEI) ameliorates progressive lossof function in non-immune-mediated renal diseases and experimentalhypertension. Little, however, is known on the potential roleof CEI in established experimental chronic glomerular immuneinjury. We therefore studied the effect of the CEI ramiprilon renal function and morphology in a model of immune mediatedglomerular injury. METHODS: The immune complex glomerulonephritis was induced in uninephrectomizedrats by intrarenal perfusion with the cationized antigen followedby an intravenous application of the antibody. This diseaseis characterized by the development of progressive albuminuriaand a nephrotic syndrome (albuminuria: immune complex glomerulonephritis342±58, control 76±18 mg/24 h; P<0.001). TheCEI by ramipril, dissolved in the drinking water, was given28 weeks after induction of the disease and treatment was continuedfor 12 weeks. RESULTS: In these experiments ramipril significantly reduced albuminexcretion (immune complex glomerulonephritis+CEI 109±16mg/24 h; P<0.01) when compared with untreated nephritic rats.Ramipril, however, did not significantly change inulin clearances(immune complex glomerulonephritis 224±67, immune complexglomerulonephritis+CEI 278±48 µ1/min/100 g bw).Glomerular structural damage expressed as glomerular damageindex was significantly greater in rats with immune complexglomerulonephritis when compared with controls (immune complexglomerulonephritis 0.91±0.13; control 0.60±0.08;P<0.05), but was uneffected by the treatment with the CEI(immune complex glomerulonephritis+CEI 1.02±0.26; control+CEI0.63±0.11). CONCLUSIONS: These data demonstrate that ramipril reduced albuminuna in amodel of immune complex glomerulonephritis; however, it failedto alter GFR and glomerular damage index. The study suggeststhat ramipril ameliorates proteinuria independently of obviousglomerular histological changes. The reduction of proteinuriais, however, associated with a significant decrease in filtrationfraction and therefore is at least partially haemodynamicallymediated.     

Decreased filtration fraction during active proliferative lupus nephritis: relation to disease activity and reversibility of renal function

Nine consecutive patients with systemic lupus erythematosus (SLE) were studied longitudinally for glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) during ten exacerbations of severe proliferative glomerulonephritis. At the onset of exacerbation, GFR decreased significantly whereas ERPF did not fall; the latter even increased in some patients. As a consequence mean filtration fraction (FF), the ratio of GFR and ERPF, fell from 0.20 to 0.10. At maximum exacerbation, both GFR and ERPF had decreased without change in FF. During remission FF rose to pre-exacerbation values as a result of increase in GFR without change in ERPF. We conclude that changes in FF reflect changes in renal haemodynamics in patients with SLE and active proliferative glomerulonephritis. Determination of FF may be of some value in assessing renal disease activity and the degree of reversibility of renal function in those patients.     

骨桥蛋白及白细胞介素-18在寻常型银屑病患者血清中的表达及临床意义

目的:检测寻常型银屑病患者外周血骨桥蛋白(OPN)、白细胞介素-18(IL-18)的表达水平,并探讨其临床意义。方法:采用酶联免疫吸附试验(ELISA)法检测30例寻常型银屑病患者(其中进行期18例,静止期12例)及30例对正常照者血清OPN、IL-18的表达水平。结果:寻常型银屑病组患者血清骨桥蛋白和IL-18的表达水平明显高于正常对照组(P<0.001);进行期银屑病患者骨桥蛋白和IL-18的表达水平明显也高于静止期(P<0.001),且骨桥蛋白、IL-18的表达水平和银屑病的活动性均呈显著正相关(P均<0.001);骨桥蛋白和IL-18的表达水平也呈显著正相关(P<0.001)。结论:OPN与IL-18在寻常型银屑病中的表达上调提示它们可能参与了寻常型银屑病的发病过程,且二者在该病的发生中起着协同作用。联合检测血清OPN、IL-18可以作为诊断银屑病活动性的有效的指标之一。     

Studies on circulating immune complexes. II: Circulating immune complexes in primary IgA nephropathy and membranoproliferative glomerulonephritis

A study of circulating immune complexes (CIC) was undertaken in 25 patients with primary IgA nephropathy and 13 patients with membranoproliferative glomerulonephritis (MPGN). Clinically, the 25 patients with IgA nephropathy were divided into two groups: the latent type, characterized by chance proteinuria and/or hematuria; and the acute onset type, revealing acute nephritic syndrome. Both the IgG class of CIC (IgG-IC) and the IgA class of CIC (IgA-IC) were measured by conglutinin binding enzyme immunoassay (C-assay). IgG-IC were found to be positive in 32% of the patients with IgA nephropathy, and in 77% of those with MPGN. IgA-IC were positive in 72% of the patients with IgA nephropathy, and in 54% of those with MPGN. Concerning the acute onset type of IgA nephropathy, IgG-IC and IgA-IC were found in 71% and 86% of the patients, respectively, which was more frequent than in the latent type group. Simultaneous presence of IgA-IC and glomerular IgA deposits detected by an immunofluorescence study was noted in 75% of the patients with IgA nephropathy. On the other hand, 78% of the patients with MPGN revealed IgG-IC and glomerular IgG deposits simultaneously. Thus, IgG-IC and IgA-IC appear to play important roles in the pathogenesis of MPGN and IgA nephropathy, respectively.     

Immune complex glomerulopathy in a child with food hypersensitivity

This report describes the occurrence of immune complex glomerulonephritis in a patient with eosinophilic gastroenteritis and food hypersensitivity. A coincident allergen injection may have been a contributing factor in the sudden development of the nephrotic syndrome. Markedly elevated levels of circulating immune complexes (greater than 6400 mg/dl) were found containing kappa-casein and bovine serum albumin (BSA), the latter predominating. Markedly elevated serum BSA hemagglutinating titers were also present (1:40,960). Cross-reacting precipitating antibodies to BSA, beef, and pork were demonstrated, but not to flounder or ovalbumin. Renal biopsy revealed immune complex glomerulonephritis with BSA, immunoglobulins M and G and complement deposited focally in the glomerular basement membrane. With strict dietary limitation of identified causative antigens and prednisone therapy, CIC levels decreased to 16,000 micrograms/dl and serum BSA antibody hemagglutinating titer fell 32-fold over a period of 15 months. There was prompt symptomatic relief and amelioration of signs of nephritis. The patient was able to consume a diet normal in protein and caloric content, and statural catch-up growth occurred. Recognition of food antigens to which the patient was hypersensitive provided a rationale for the relief of the gastrointestinal disturbance, growth stunting, and renal disease.     

中国肾小球滤过率评估方程在慢性肾小球肾炎患者的适用性评价

目的：评价现有在中国人群基础上开发的肾小球滤过率（GFR）评估方程在慢性肾小球肾炎患者的适用性。方法：选择143例慢性肾小球肾炎患者,用中国方程、瑞金方程、MDRD1方程和简化MDRD方程,分别计算GFR值,与^99mTc—DTPA测的GFR（sGFR）进行比较。结果：Bland—Altman分析显示MDRD1方程和瑞金方程估计的GFR和sGFR的一致性较好,但所有各方程估计的GFR和出FR的一致性限度均超过事先规定的专业界值。线性回归结果显示,MDRD1方程和瑞金方程估测的GFR与X轴的斜率较其他方程更接近0。在所有方程中,MDRD1方程和中国9方程偏差较小,瑞金方程估测GFR30％符合率和50％符合率均最高,但瑞金方程估测GFR30％符合率依然低于70％。在慢性肾脏病不同分期中,瑞金方程和MDRD1方程较其他方程有较小的偏差和更优的准确性。结论：当血肌酐的测定方法为酶法时,如直接应用现有在中国人群基础上开发的肾小球滤过率评估方程评估慢性肾小球肾炎患者肾功能,可能会产生明显的偏差。     

A comparative immunologic study of IgA nephropathy

A conglutinin binding assay has been used to detect circulating immune complexes (CIC) containing IgA, IgG, or IgM in sera from patients with IgA nephropathy. IgA class CIC were detected in 40.7% of patient. IgG class CIC were detected only in patients with glomercular IgG deposits. IgM class CIC were detected more often in patients with glomerular IgM deposits than in patients without glomerular IgM deposits. These results demonstrate an association between the immunoglobulin in CIC and those in glomerular deposits. CIC were not detected in sera from most patients with IgA nephropathy by a Clq binding assay, however, since this assay does not detect IgA class CIC. Immunoelectronmicroscopic studies of IgA nephropathy have shown that C3 deposits are localized to the same areas as IgA deposits. In conclusion, we suggest that mesangial IgA deposits are composed of immune complexes and may be derived from CIC.