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.     

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.     

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.     

Circulating immune complexes and complement breakdown products in childhood IgA nephropathy]

Circulating immune complexes (CIC), mainly IgA-CIC have been frequently detected in IgA nephropathy and recently increased levels of C3 fragments which indicate C3 activation have been reported. However, little is known about the relationship between CIC and complement activation. We determined CIC by the solid-phase anti-C3 Facb enzyme immunoassay in 37 children with IgA nephropathy to investigate the relationship between CIC and clinical and/or histological findings, and also determined C3 fragments whether CIC correlate with complement activation. IgA-CIC were detected in 78% (27/37) with a mean level of 11.9 +/- 3.9 micrograms/ml, which was significantly higher than other glomerular diseases (P less than 0.05). IgA-CIC levels were also found significantly higher in 27 cases with proteinuria than in 10 cases without proteinuria (P less than 0.05). IgG-CIC were detected in 67% (12/18) with a mean level of 4.1 +/- 2.6 micrograms/ml, which was not significantly different from other glomerular diseases. No striking correlation was noted to exist between CIC levels at renal biopsy and the histological severity, because CIC are often present intermittently. C3d was quantitated by the rocket immunoelectrophoresis and C3 by the single radial immunodiffusion to determine the C3d/C3 ratio. The mean value of C3d/C3 was 0.63 +/- 0.19 which was significantly higher than a corresponding value for 15 healthy controls of 0.27 +/- 0.06 (P less than 0.05). Levels of IgA-CIC were found to have a significant positive correlation between C3d/C3 determined simultaneously in 33 cases (r = 0.43, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Circulating anti-entactin antibodies in patients with glomerulonephritis

Sera from 305 consecutive patients in a renal biopsy series were analyzed for the presence of anti-entactin antibodies by ELISA. Of these patients, 59% had primary glomerulonephritis, 21% had secondary glomerulonephritis, while 20% had other nephropathies (noninflammatory conditions like amyloidosis, diabetic nephropathy, nephrosclerosis, etc.). Forty-one of these patients (13.4%) were positive for IgG/IgM antibodies against entactin: 60% of them had primary glomerulonephritis, 35% had secondary glomerulonephritis, while the remaining 3 patients had other nephropathies. Fifteen (70%) of the 23 patients with primary glomerulonephritis had proliferative glomerulonephritis (PGN), whereas 13 (87%) of the 15 patients with secondary glomerulonephritis were due to systemic connective tissue diseases (SCTD): 7 due to SLE, 4 due to SLE like SCTD and two due to other SCTD. There was a peak of incidence corresponding to the group aged 18 to 30 years. A majority of these patients (12 of the total 17) had primary glomerulonephritis and were associated with nephrotic or subnephrotic grade proteinuria, poorly or nonresponsive to immunosuppressive treatment and associated, in several cases, with progressive deterioration of renal function. In addition, there was a tendency to another peak in the age group 51 to 60 years. Most of these patients (6 of the total 8) had glomerulonephritis secondary, mainly, to SLE or SLE like SCTD with milder degree of proteinuria and better preserved renal functions. Anti-entactin antibodies were not found in certain glomerulonephritides like IgA nephropathy and those secondary to systemic vasculitides and in control subjects (healthy subjects, and patients with a variety of non-renal disorders including inflammatory diseases).(ABSTRACT TRUNCATED AT 250 WORDS)     

Detection of circulating immune complexes in patients with glomerulonephritis.

A panel of three immune complex (IC) assays was used in this study to test sera from patients with glomerulonephritis (GN): the Raji cell radioimmune assay (IRCA), the radio-labeled C1q binding assay (IC1qBA), and the microcomplement consumption test (MCT). The sensitivity and specificity of each assay was evaluated in preliminary studies, and the greater sensitivity (5 to 10microgram of aggreagated human gamma-globulin (AHG) per ml of serum) and IgG specificity of the IRCA was apparent. Problems related to the preliminary heat inactivation of test sera, the interaction of C1q with substances other than IC, and the effects of suboptimal storage of test sera were experienced with the MCT and, to a lesser extent the IC1qBA. The individual reactivities of the different assays were exploited by using them in combination. Thus ICs were detected by one or more of the assays in 87% of patients with systemic lupus erythematosus (SLE), 65% of patients with GN associated with other systemic diseases, and 39% of patients with primary GN. ICs were detected more frequently in patients with acute GN than chronic GN, and in patients with low serum C3, C4, and properdin factor B (C3PA) levels.     

Response of circulating immune complexes to food challenge in relapsing IgA nephropathy

The response of circulating immune complexes (CIC) to food challenge was assessed in 15 subjects with IgA nephropathy (IgAN) and recurrent macroscopic haematuria. CIC were measured by solid-phase C1q binding assay (SP-C1q), immunoglobulin class-specific polyethylene glycol (PEG) precipitation assays (PEG-G, PEG-A, PEG-M) and by an antigen (ovalbumin)-specific radioimmunoassay after acid dissociation (OA-IC). CIC were measured when the subjects were fasting and hourly for 6 h after a test meal containing eggs. All 15 subjects were tested while clinically quiescent (remission) and 6 were tested again during episodes of macroscopic haematuria (relapse). The PEG-A CIC response to food challenge was significantly exaggerated in IgAN remission compared with controls at 3–6 h after food. There were also non-significant increases in PEG-G, though not in PEG-M. Paired data showed further exaggeration of PEG-G, PEG-A and PEG-M responses to food during IgAN relapse, but significance was not attained if the findings in 1 subject were separated. In this individual a florid clinical relapse with transient decline in renal function was associated with very high levels of PEG-IC, and only in this patient in relapse was OA-IC detectable, confirming that some PEG-precipitated material represented antigen-antibody complexes containing food antigen.     

Urinary excretion of type IV collagen as a specific indicator of the progression of diabetic nephropathy

AIMS AND METHODS: This study was carried out to clarify whether the urinary excretion of type IV collagen (u-IV collagen) detected by specific radioimmunoassay, can be used as an indicator for the progression of diabetic nephropathy. RESULTS: u-IV collagen was higher in diabetic subjects with microalbuminuria and overt proteinuria than those with normoalbuminuria, IgA nephropathy, membranoproliferative glomerulonephritis, membranous nephropathy, or control normal subjects. u-IV collagen was positively correlated with serum and urinary beta(2)-microglobulin and negatively with creatinine clearance only in diabetic patients, but not in patients with other glomerular diseases. The serum type IV collagen was not different between all the groups, and not correlated with its urinary excretion. In the advanced diabetic nephropathy, immunoreactive type IV collagen was detected in glomerular basement membrane (GBM), tubular basement membrane and Bowman's capsule much more than that in the normal kidney. CONCLUSION: These findings indicated increased production and degeneration of type IV collagen in diabetic nephropathy. It is suggested that augmented turnover of type IV collagen in GBM and tubular basement membrane results in increased concentrations of free u-IV collagen. Therefore, measurement of u-IV collagen may be a useful, specific indicator of the progression of diabetic nephropathy.     

肾活检患者451例临床与病理构成对比分析

目的 分析珠海地区肾脏疾病的病理及临床特点.方法 回顾性分析我院451例肾活检患者的临床及病理资料,探讨其病因、临床特点及病理类型的关系.结果 451例肾活检患者中,男、女高峰发病年龄为19～37岁,分别占59%及65%.原发性肾小球疾病共369例（占81.81%）,临床类型排在前3位的依次为无症状血尿、蛋白尿149例（占40.38%）、慢性肾小球肾炎104例（占28.18%）、肾病综合征76例（占20.60%）,病理类型排在前3位的依次为IgA肾病251例（占68.02%）、系膜增生性肾小球肾炎（MsPGN）33例（占8.94%）、微小病变型肾病（MCD）24例（占6.50%）;继发性肾小球疾病69例（占15.30%）,临床类型排在前3位的依次为狼疮肾炎26例（占37.68%）、乙型肝炎相关性肾小球肾炎24例（占34.78%）、紫癜肾炎9例（占13.04%）.结论 原发性肾小球疾病是目前最主要的肾小球疾病,IgA肾病在原发性肾脏疾病中发病率最高,继发性肾小球疾病中狼疮肾炎排在首位.     

Presence of circulating immune complexes in the classic form of hemolytic uremic syndrome: a constant finding

In an attempt to further study the possible contribution of circulating immune complexes (CIC) in the pathogenesis of the classic form of hemolytic uremic syndrome, 9 patients were studied during the acute phase of the diseases. C1q solid-phase ELISA and conglutinin solid-phase ELISA, were used to measure the levels of immune complexes. All 9 were positive in one or both assays. No correlation was found between the levels of CIC and the clinical severity of the disease. The constant finding of positive CIC in these patients might represent an epiphenomenon, point out the postinfectious nature of this disease but also suggest a possible pathogenic role.     

豫琼两地原发性肾小球疾病病理类型的变迁对比及临床分析

目的 回顾性分析豫北地区及海南两地近12年原发性肾小球疾病疾病谱的构成演变特点及其意义.方法 分别收集2008年1月至2019年12月于新乡医学院第一附属医院及海南医学院第一附属医院经临床及肾活检诊断为原发性肾小球疾病3985例患者的临床及病理资料,并对其进行对比分析,根据年份分为2008年至2011年、2012年至2...     

HIV-associated immune complex glomerulonephritis with "lupus-like" features: a clinicopathologic study of 14 cases

BACKGROUND: While the most common glomerular lesion associated with human immunodeficiency virus (HIV) infection is collapsing focal segmental glomerulosclerosis (FSGS) [HIV-associated nephropathy (HIVAN)], immune complex-mediated forms of glomerulonephritis have been increasingly reported. One form of glomerulonephritis that has been described in the HIV-infected population is immune complex glomerulonephritis with "lupus-like" features, characterized by histologic, immunohistologic, and ultrastructural features resembling lupus nephritis, but occurring in patients without evidence of systemic lupus erythematosus (SLE). Data regarding clinical outcomes in patients with this form of glomerulonephritis are very limited. METHODS: We reviewed pathology reports for all native renal biopsy specimens from HIV-positive patients processed at our center from January 1999 through December 2003. Of 77 total specimens, 14 met the following criteria for lupus-like glomerulonephritis: (1) immunofluorescence microscopy showed granular glomerular staining for IgG, IgA, IgM, C3 and C1q, with > or=1+ (0 to 4+ scale) staining for C1q; and (2) the patient's serum was negative for antinuclear antibodies (ANA), or weakly positive (titer < or =1:80) for ANA and negative for antidouble-stranded DNA. RESULTS: Clinically, ten of the 14 patients with lupus-like glomerulonephritis presented with nephrotic syndrome, all had microscopic hematuria, and nine had serum creatinine >3.0 mg/dL. All but one were African American. Histologically, seven biopsies showed diffuse proliferative glomerulonephritis, six focal proliferative glomerulonephritis, and one membranous nephropathy. All but two biopsies showed moderate or severe chronic change, and three showed concurrent HIVAN. Ten of the 14 patients developed end-stage renal disease (ESRD) within 1 year of the biopsy. Nine of these ten patients presented with proteinuria >5.0 g/24 hours and nephrotic syndrome, while three of four patients who did not develop ESRD had proteinuria < or =3.0 g/24 hours. CONCLUSION: Lupus-like glomerulonephritis, defined by immunohistologic features and absence of serologic evidence of SLE, is not an uncommon form of glomerular disease in HIV-infected patients undergoing a renal biopsy. Renal outcomes in these patients were poor, although this may be due largely to most patients presenting with advanced disease.     

四川地区肾活检2330例临床病理分析

目的：探讨四川地区肾穿刺活检病理类型的分布特点以及疾病谱的变迁。方法回顾性分析2330例肾活检患者的临床病理资料,分析本地区肾脏疾病的临床病理特征。结果2330例肾活检患者中,男女比例为1∶1.15,发病高峰年龄为20~40岁。2330例患者中,原发性肾小球疾病1896例（占81.37%）,常见的病理类型依次为 IgA 肾病820例（占35.19%）、系膜增生性肾小球肾炎372例（占15.97%）、膜性肾病298例（占12.79%）、微小病变肾病200例（占8.58%）和局灶节段性肾小球硬化症78例（占3.35%）;继发性肾小球疾病367例（占15.75%）,以狼疮性肾炎最常见（134例,占5.88%）,其次为紫癜性肾炎127例（占5.45%）、糖尿病肾脏疾病35例（占1.5%）和淀粉样变性肾病20例（占0.86%）;肾小管间质疾病50例（占2.15%）;遗传性肾病17例（占0.73%）。2330例肾脏疾病患者的临床表现依次为肾病综合征1015例（占43.56%）、慢性肾炎综合征681例（占29.22%）、急性肾炎综合征392例（占16.82%）、隐匿性肾小球肾炎121例（占5.29%）、慢性肾衰竭72例（占3.09%）、急性肾衰竭47例（占2.02%）。近年来,膜性肾病构成比呈逐渐增加趋势。结论本地区肾脏疾病多见于青壮年,以原发性肾小球疾病最常见,其中 IgA 肾病和系膜增生性肾小球肾炎是最多见的病理类型,膜性肾病的检出率有增高趋势。继发性肾小球疾病以狼疮肾炎和紫癜性肾炎最常见。     

Immunohistochemical analysis of extracellular components on the glomerular sclerosis in patients with glomerulonephritis and diabetic nephropathy

Immunofluorescence and immunoperoxidase staining were carried out to determine the correlations between the progression of glomerular sclerosis and changes in the amount and distribution of glomerular extracellular components, such as Type I, III, IV, V, VI collagen, laminin (LN) and fibronectin (FN) in patients with various types of glomerulonephritis and diabetic nephropathy. Six patients with IgA nephropathy, four patients with membrano-proliferative glomerulonephritis, four patients with rapidly progressive glomerulonephritis and six patients with diabetic nephropathy were examined. The intensity and distribution of Type IV collagen, LN and FN were similar between the glomeruli from normal individuals and patients with mild stages of glomerulonephritis and diabetic nephropathy. However, staining of Type I, III or V collagen was not observed in the glomeruli from normal individuals and such patients. In more advanced stages of glomerulonephritis and diabetic nephropathy, the amounts of Types IV and VI collagen, LN and FN were increased markedly in the mesangium, and their distribution extended along the glomerular capillary walls. The intensity of Type IV collagen, LN or FN in the nodular sclerotic lesions of glomeruli was decreased significantly in patients with glomerulonephritis and diabetic nephropathy. On the other hand, staining of Types I, III and V collagen was observed focally in the sclerotic or hyalinotic glomeruli and around such glomeruli in these patients. In light microscopic examinations, the patients who had marked staining of Type I, III or V collagen by immunofluorescence showed severe damage of the basement membrane in Bowman's capsules. It is concluded that hyperproduction and/or infiltration of interstitial collagens, i.e. Types I, III and V collagen, is closely linked to the progression of glomerular sclerosis and hyalinosis in patients with various types of glomerulonephritis and diabetic nephropathy.     

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.     

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.     

Studies of circulating immune complexes and lymphocyte subpopulations in childhood IgM mesangial nephropathy

T cell subsets, serum immunoglobulin (IgM) level, IgM-bearing lymphocytes, and circulating immune complexes (CIC) were studied in 12 children who suffered from IgM mesangial nephropathy (IgMN) during the acute nephrotic phase, in remission and relapse. Frequent relapses were observed in 11 cases, and 1 was partially responsive to steroid treatment. IgMN was diagnosed by the consistent pattern of IgM deposition by all four FITC-labelled antihuman IgM antibodies from rabbits and goats supplied by four different companies and by the 100% positivity of electron-dense mesangial deposits in an identical localization and distribution pattern of kidney biopsy specimen. CIC were detected by the 3.5% polyethylene glycol method. In sera from 12 patients IgM CIC were detected in 8 cases during the acute nephrotic phase. High levels of C3 CIC and C4 CIC were also found in these cases during the acute nephrotic phase. The CIC were undetectable in remission. Only 3 cases were detectable at low levels of IgM CIC during the second relapse. High serum IgM levels and IgM-bearing lymphocytes were noted in these patients. The patients also had a significant increase of OKT8 cells and a decrease in the OKT4/OKT8 ratio during the acute phase and in relapse. Taken together, the immunopathologic and clinical features suggest that IgMN is a disease entity with a chiefly classical pathway activation of complement components. The correlation between the changes of T cell subsets and the disease activity in IgMN suggests that this may serve as a therapeutic and prognostic guide.     

Primary antiphospholipid antibody syndrome and mesangial IgA glomerulonephritis

The antiphospholipid antibody syndrome (APS) is characterized by recurrent thrombosis, fetal loss, multiorgan involvement, and the presence of lupus anticoagulant and/or anticardiolipin antibody. When not associated with systemic lupus erythematosus, other collagen diseases, or ingestion of medications, the condition is called primary APS. The kidney may be involved in the APS syndrome with acute nephritis and renal failure. The cases with renal biopsy studies have shown variable glomerular morphology, ranging from mild mesangial changes to a diffuse endocapillary proliferative glomerulonephritis. The most frequent lesion is thrombotic microangiopathy or features seen in the hemolytic uremic syndrome. Apart from fibrin thrombus deposition, only a few cases have shown focal and segmental deposits of IgG and/or IgM and/or C3. We describe a patient with primary APS who had thrombosis with lower limb amputation and acute renal failure. The renal biopsy specimen showed a focal proliferative glomerulonephritis with endothelial proliferation and damage, with diffuse heavy mesangial deposits of IgA and fibrinogen. This case with diabetes mellitus, but without diabetic nephropathy, represents the occurrence of primary APS and mesangial IgA nephropathy which potentiated the renal injury, leading to acute renal failure. The relationship to the Henoch-Sch?nlein syndrome is discussed.     

Anti-T cell antibodies in primary glomerulonephritis

Lymphocytotoxic antibodies are frequently found in systemic lupus erythematosus (SLE) and several viral infections and are presumed to play an important role in the pathogenesis of these diseases through the modulation of lymphocyte subsets. Accordingly, using a slightly modified E rosette inhibition test, we investigated anti-T cell antibodies in lupus nephritis and various forms of primary glomerulonephritis to determine the correlation with lymphocyte subsets, macrophages and serum immune complexes. Patients with active lupus nephritis showed the highest titers and incidences of anti-T cell antibodies. Titers and incidences in primary glomerulonephritis were less than in lupus nephritis. Among the various forms of glomerulonephritis, the titers and incidences were greatest in membrano-proliferative glomerulonephritis and minimal change nephrotic syndrome, next in membranous glomerulonephritis, and least in IgA glomerulonephritis. The antibodies were positive in the stages of nephrotic syndrome or macrohematuria of these diseases. If detected, antibodies were associated with decreased T and T gamma cells, increased numbers of macrophages and elevated serum immune complexes. These data suggest that anti-T cell antibodies are cytotoxic to T and T gamma lymphocytes and modulate the immunological network, thus playing an important role in the pathogenesis of various forms of glomerulonephritis.     

Endocapillary proliferative glomerulonephritis with crescent formation and concurrent tubulointerstitial nephritis complicating retroperitoneal fibrosis with a high serum level of IgG4

Renal lesions of IgG4-related disease have been reported recently. Most of them are tubulointerstitial nephritis, and a definite glomerulonephritis complicating IgG4-related disease is very rare. We report here a case of definite glomerulonephritis and concurrent tubulointerstitial nephritis complicating retroperitoneal fibrosis with a high serum level of IgG4. A 68-year-old Japanese woman was referred to our hospital for investigation of anasarca. We diagnosed her disease as a nephrotic syndrome and left hydroureteronephrosis due to retroperitoneal fibrosis. Her laboratory data revealed a high serum level of IgG4, renal injury, hypoproteinemia, hypocomplementemia, a positive finding of circulating immunocomplex (CIC), and negative findings ofautologous antibodies suggesting systemic lupus erythematosus (SLE) or Sj?gren's syndrome (SS). A diagnosis of SLE or SS could not be made clinically. Right renal biopsy revealed endocapillary proliferative glomerulonephritis with crescent formation and concurrent tubulointerstitial nephritis. Infiltration of plasma cells in interstitium was more conspicuous than seen with ordinary tubulointerstitial nephritis, and in most of them IgG4 was positive. We placed a percutaneous nephrostomy catheter in her left kidney, and prescribed prednisolone and cyclosporine. The responses to prednisolone and cyclosporine therapies were very good. Further studies are needed to clarify the relationship between glomerulonephritis and IgG4-related disease. However, when considering renal lesions of IgG4-related disease, we think that hypocomplementemia, a positive finding of CIC, negative findings of autologous antibodies suggesting SLE or SS, conspicuous interstitial infiltration of IgG4-positive plasma cells, and a good response to steroid or immunosuppressant therapy are key points.