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.     

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.     

Circulating immune complexes during various forms of renal allograft rejection episodes

Previous reports on the nephritogenic and immunological enhancing capacity of posttransplant circulating immune complexes (CICs) are conflicting and have been confined to the study of acute rejection episode (AR). This study was undertaken to assess the nephritogenicity of CICs in patients undergoing accelerated acute rejection (AAR) and chronic rejection (CR) episodes.We also assessed the possible role of CICs as mediators of immunological enhancement by assessing CIC levels in long-term-stable allograft recipients. To asses the nephritiogenic role of CICs, 98 CIC determinations were performed on 49 serum samples from 41 pediatric renal transplant recipients using the C1q solid-phase assay (C1q-SPA) and the Raji cell radioimmunoassay (Raji-RIA). Serum samples from normal subjects served as controls. No recipient undergoing AAR had evidence of CICs by eigher assay. 5 of 21 (23.8%) recipients undergoing CR had positive CIC levels in the Raji-RIA, while 4 of 21 (19%) recipients had positive CICs inthe C1q-SPA. There was no statistically significant correlation of CIC levels with long-term allograft function. In addition, there was no evidence supporting antithymocyte globulin as an immunogen in patients demonstrating posttransplant CICs. In summary, CICs do not appear to be an important mediator of AAR or CR episodes, and CICs were not routinely detected in patients with good long-term allograft function.     

Circulating immune complexes in intracranial neoplasms

Summary The levels of circulating immune complexes (CIC) were assayed in the sera of 109 patients with intracranial space occupying lesions. The CIC levels were significantly increased in all the brain tumours. After treatment, the CIC levels were still significantly increased when compared to the controls but showed no change when compared to their respective pre-operative values. Further, no change was observed in the CIC levels between the malignant and benign tumour case. Moreover, in brain tumours, 90% of the CIC precipitate consisted of IgG. However, the CIC levels fail to prognosticate the process of the disease in these patients.     

Circulating immune complexes in patients following clinically curative resection of colorectal cancer.

Sixty-nine patients have been followed prospectively after curative resection of Dukes-Kirklin B-2 or C colorectal cancer. Serial plasma samples were studied in selected patients to determine changes in circulating immune complex concentrations (CIC) following primary tumor resection, and to compare serial plasma CIC and carcinoembryonic antigen (CEA) levels. CIC was determined in an average of seven serial samples per patient by inhibition of antibody-dependent cell-mediated cytotoxicity (ADCC). CEA assays were performed by the Hanson Z-gel method. Two distinct patterns of serial CIC have emerged. In seven patients with no known tumor recurrences, serial CEA levels and CIC oscillated regularly and were inversely related. In seven of eight patients whose tumors recurred, both CEA and CIC rose together. In three patients with elevated plasma CEA levels due to inflammatory bowel disease, serial Ag-Ab complex concentrations did not vary, nor did separated Ag or Ab fractions inhibit ADCC. These data suggest that, in patients following curative resection of colorectal cancer, serial changes in circulating immune complexes may discriminate between transient CEA elevations which occur despite no known tumor recurrence and tumor recurrence which is beyond the capacity of adequate host antitumor defense.     

Von Willebrand factor and factor XIII in children with Henoch-Schonlein purpura

Levels of von Willebrand factor antigen (vWf: Ag) and factor XIII activity (F XIII) were studied in relation to the severity of clinical symptoms (scored from 0 to 3) and to immunological parameters [IgA, C3, C4, and circulating immune complexes (CIC) in 16 children (7 males, 9 females, aged 3–11 years) with Henoch-Schonlein purpura (HSP) at presentation. vWf: Ag was increased in 7 patients, F XIII activity was decreased in 6. In all children we found high levels of IgA, while C3 and C4 levels were normal; CIC were elevated in 11. vWf: Ag correlated with clinical score and with IgA and CIC, probably as a result of immune-mediated endothelial cell damage. The haemostatic alterations observed in HSP are important for understanding the pathophysiology of the disease.     

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.     

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.     

Immune complexes and complement activation following rupture of intracranial saccular aneurysms

Circulating immune complexes (CIC) and complement activation (plasma C3d levels) were monitored during a 2-week period in patients with ruptured cerebral aneurysms and also in patients with cerebral hematoma unrelated to saccular aneurysms. Thirteen of 18 aneurysm patients were found to have CIC on admission as compared to three of 21 healthy blood donors (p less than 0.001). The presence of CIC in aneurysm patients was associated with a poor prognosis. Eight of nine patients who developed angiographic vasospasm had CIC on admission compared with one of four without vasospasm. Patients with vasospasm showed a twofold increase in plasma C3d levels at the time when the spasm occurred, whereas no significant changes in the C3d concentration could be demonstrated in aneurysm patients without spasm or in patients with hematoma unrelated to aneurysm rupture. These findings suggest that immunological processes involving complement-activating immune complexes are involved in the pathogenesis of cerebral vasospasm following rupture of saccular aneurysms.     

Scanning electron microscopy of glomerular and non glomerular red blood cells

Circulating immune complexes (CIC) were found in 12% of sera from 56 patients before renal allotransplantation. No relationship was found between the presence of CIC before transplantation and the 6 months graft survival. CIC were detected in serial blood samples obtained from 8 out of 30 patients (27%) during the first 6 weeks after transplantation. No relationship was found between CIC and acute rejection episodes. In 3 patients CIC were associated with acute infections. Thus the appearance of CIC shortly after renal transplantation may be an indicator of infection rather than rejection. CIC were detected in 32% of 50 renal transplant recipients who had functioning grafts for more than one year. No association was found between CIC and decreasing graft function, blood pressure or the recipient's original disease. CIC were frequently detected in patients with proteinuria above 3 g/24 hr suggesting a role of CIC in some cases of late renal graft failure.     

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.     

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.     

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)     

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.     

Studies on circulating immune complexes. III: Kinetics of the immunoglobulin class of circulating immune complexes in systemic lupus erythematosus

The IgG, IgA and IgM classes of circulating immune complexes (CIC) were examined in 49 patients with systemic lupus erythematosus (SLE). The presence of the IgG class of CIC (IgG-IC), IgA class of CIC (IgA-IC) and IgM class of CIC (IgM-IC) was observed in 39.4%, 24.2% and 35.3%, respectively. During the course of the disease, the levels of IgG-IC and IgM-IC remained generally higher than that of IgA-IC. The patients were divided into three groups, according to the changes in IgG-IC. Group 1: these had IgG-IC persistently, associated with clinically active features (active stage). The presence of IgA-IC was occasionally transient, although IgM-IC did coexist. Group 2: these showed an increased level of IgG-IC, associated with a tendency to relapse (flaring up stage). IgM-IC disappeared occasionally, although IgA-IC appeared to be persistently present. Group 3: these showed levels of IgG-IC which decreased or disappeared and the clinical activity tended to subside (remissible and inactive stages). All classes of CIC tended to disappear. That is to say, IgG-IC, then IgA-IC, and finally IgM-IC decreased in that order. Either IgA-IC or IgM-IC was present alone persistently in a few cases. The correlations between each class of CIC and the immunological parameters were investigated. IgG-IC and IgM-IC were closely related to anti-nuclear antibody, but not to anti-DNA antibody.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serial determinations of melanoma tumor-associated antigen and antibody in patients with stage I melanoma

The correlation of circulating immune complexes (CICs) and the clinical course of malignant melanoma has not been consistent when using nonspecific assays for CIC. To improve predictability, serial serum samples from patients with pathologic stage I melanoma were analyzed for the presence of antimelanoma tumor-associated antigen (TAA) antibody by direct radioimmunoassay and for the presence of melanoma TAA in CIC by the antigen competition method. Immunochemically characterized TAA was isolated from the spent culture medium of a melanoma cell line. Seventy-five percent of patients with melanoma TAA-specific immune complex (IC) had recurrences, while 71% of patients without melanoma TAA-specific IC remained free of disease for prolonged periods (up to 14 years of follow-up). Anti-TAA antibody titers did not correlate with disease recurrence. Our results demonstrate a correlation with melanoma TAA-specific IC and disease recurrence. The absence of melanoma TAA-specific IC is associated with a low risk of recurrence. Fluctuations in melanoma TAA-specific IC levels indicate a dynamic tumor host immunobiology and the need for serial follow-up.     

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.     

Detection of circulating immune complexes by polyethyleneglycol precipitations complement consumption test in urological malignant diseases

Circulating immune complexes (CIC) were detected and quantitated in 49 patients with urological malignant diseases (9 cases of renal cell cancer, 3 cases of renal pelvic and ureter cancer, 21 cases of bladder cancer and 16 cases of prostatic cancer), 9 patients with urological benign diseases and in normal subjects by the polyethylene-glycol precipitation complement consumption test (PEG-CC test). The average CIC level was 2.7 +/- 3.0% in 18 normal subjects and the normal range was less than 10% of the CIC level. CIC level of patients with renal cell cancer was 14.3 +/- 20.1%, being elevated in 3 of the 9 patients, that of patients with renal pelvic and ureter cancer was 4.7 +/- 4.6%, being within the normal range in 3 cases, that of patients with bladder cancer was 4.7 +/- 4.4%, being elevated in 1 of 21 patients, and that of patients with prostatic cancer was 8.9 +/- 15.4%, being elevated in 3 of 16 patients. In urological malignant diseases such as renal cell cancer and prostatic cancer the CIC values were relatively high.     

Comparative informative value of the leukogram and the level of circulating immune complexes in patients with acute appendicitis

Data of the leukocyte reaction and amount of circulating immune complexes (CIC) in blood serum of patients with acute appendicitis were studied. The determination of CIC is shown to be more informative concerning inflammatory changes in the vermiform process. The method of determination of CIC in blood serum is simple, not time-taking and may be used in urgent surgery as an additional method of diagnosis of acute appendicitis.     

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.