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.     

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.     

Use of radioimmunoassay for the detection of circulating antistreptococcal antibody in patients with glomerulonephritis

A method of radioimmunologic quantitation of antibodies to streptococcal antigen separated from the cell wall extract of group A type T₁₂ strain has been developed. The highest values of radioactive antigen binding were observed in acute glomerulonephritis (75%), as compared to chronic glomerulonephritis in which values of 25% to 56% were found depending on the morphology of renal changes. It was shown that none of the patients with pyelonephritis, Alport's syndrome, lupoid nephritis and polycystic renal disease had elevated antistreptococcal antibody levels. In contrast to this, all patients with tonsillitis and proteinuria exhibited increased titre of this antibody.It was shown that the antigen is related neither to M-protein nor to group A polysaccharide and that it is not type-specific because the binding of antigen T₁₂ may be inhibited by the antigen produced from strain T₅. Although the antigen is not type-specific, some differences in the response to antigens prepared from various types of streptococci in patients with different form of chronic glomerulonephritis are observed.     

Cationic antigens in poststreptococcal glomerulonephritis

Antigen charge is an important factor in the pathogenesis of experimental immune complex glomerulonephritis. Its potential role in man was investigated in post-streptococcal glomerulonephritis, a disease where the causative agent is known. Cationic, extracellular streptococcal antigens were detected in 8 of 18 renal biopsies from patients with acute poststreptococcal glomerulonephritis (APSGN). The antigen was found mainly in earlier biopsies in which both IgG and IgM were present. Patients' sera taken at the time of biopsy contained antibody to cationic, streptococcal antigens. Cationic moieties are known to have affinity for the glomerular basement membrane and it is possible that the type of antigen described here initiates APSGN via in situ immune complex formation.     

Psoriasis vulgaris associated with mesangiocapillary glomerulonephritis

A patient experienced the concomitant onset of psoriasis vulgaris and mesangiocapillary glomerulonephritis (MCGN) with massive proteinuria. Laboratory examination revealed reduced glomerular filtration rate (GFR), elevated serum IgG, IgA and circulating immune complex (CIC) levels. Both diseases responded promptly to combined therapy with prednisolone, urokinase and plasma exchange. CIC and GFR were normalized with histological improvement. To our knowledge, this is the first case of glomerulonephritis, which can be related to psoriasis vulgaris through an immune mechanism.     

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.     

A new hypothesis about the pathogenesis of chronic glomerulonephritis

Extensive trials have been done to find a relationship between chronic glomerulonephritis and streptococcal tonsillitis. Serological, epidemiological and other studies failed to prove this relationship in the majority of instances. We have observed that definite evidence of pyelonephritis, with disparity between the function of both kidneys and bacteriuria, was present in a large number of the cases diagnosed histologically of the kidney can lead to a proliferative glomerulopathy. We suggest that previous haematogenous renal parenchymal infection or pyelonephritis is responsible for the glomerulopathy of many of the cases diagnosed as chronic glomerulonephritis of unknown etiology or presumably related to streptococcal tonsillitis or the so-called subclinical acute poststreptococcal glomerulonephritis.     

Extracellular neuraminidase production of streptococci associated with acute nephritis

The possibility that streptococcal neuraminidase has a pathogenic role in acute poststreptococcal glomerulonephritis is reviewed. Experimental and clinical evidence suggesting autologous immune phenomena and anti-Ig reactivity in this disease is discussed. Neuraminidase may also induce sialic acid depletion that would be expected to result in changes of the electrical charge in the immune complex as well as in the glomerular polyanion filtration barrier. The nature of these changes will facilitate penetrability of material with nephritogenic potential. Neuraminidase production was detected in the majority of streptococcal isolates obtained from patients with glomerulonephritis and the best substrate for screening purposes appears to be bovine submaxillary gland mucin. On the basis of available evidence, it is suggested that the development of glomerulonephritis after streptococcal infection probably does not depend on neuraminidase production by the bacteria; however, this enzyme may be responsible for the anti-Ig reactivity demonstrated in some patients and thereby influence the course of the disease.     

A rare case of postinfectious glomerulonephritis caused by pneumococcus in an adult patient

Postinfectious glomerulonephritis (PIGN) is commonly seen as a complication of infection with nephritogenic strains of group A streptococci, mostly with Streptococcus pyogenes. Pneumococcal pneumonia leading to glomerulonephritis has been reported in the pediatric literature, but only one adult case has been previously reported. We are presenting a case of postinfectious glomerulonephritis caused by pneumococcal pneumonia in an adult. In the present case, other possible etiologies of nephritic syndrome were ruled out with negative antineutrophilic cytoplasmic antibody (ANCA), anti-glomerular basement membrane antibody (Anti-GBM), antistreptolysin O (ASO), antinuclear antibody (ANA), HIV and viral hepatitis profile. The low CH50 indicated a complement-mediated injury. Renal biopsy was done showing immune complex-mediated crescentic glomerulonephritis consistent with postinfectious etiology. The patient received pulse dose steroids for 5 days followed by oral steroids. His urinary output improved along with normalization of his renal function, therefore dialysis was discontinued. We are presenting this case to alert clinicians to the possibility of postinfectious glomerulonephritis following pneumococcal pneumonia and to report the successful use of steroid therapy in such a situation.     

100例新月体肾炎的免疫病理分型及临床病理分析

目的：了解新月体性肾炎的免疫病理分型及其临床病理特点。方法：对我科近10年来经肾活检确诊的100例新月体性肾炎进行回顾性分析,对患者血清进行抗中性粒细胞胞浆抗体（ANCA）和抗肾小球基底膜（GBM）抗体的检测。结果：100例患者中21％为抗GBM抗体型,其中6／21例同时合并ANCA阳性;47％为免疫复合物型,其中9／47型ANCA阳性;32％为少免疫沉积型,其中17／32例为ANCA阳性小血管炎。3种类型相比,抗GBM抗体型以青年男性为主,多有少尿或无尿（P＜0．05）,肾小球受累受为广泛（P＜0．001）,预后差（P＜0．001）。免疫复合物型以中青年为主,多表现为肾病综合征（P＜0．01）,强化免疫抑制治疗有效。少免疫沉积型以中老年为主,有多系统受累（P＜0．05）,治疗效果相对较好。结论：我国新月体肾炎中虽仍以免疫复合物型为主,但抗GBM抗体型和ANCA阳性小血管炎并不少见。肾活检免疫病理和血清自身抗体的联合应用对新月体肾炎进行分类更接近病因学诊断。     

IgG, IgA and IgM rheumatoid factors in patients with glomerulonephritis

Rheumatoid factors (RF), autoantibodies to IgG, have been postulated to have some pathogenetic role in the development of some types of glomerulonephritis. A simple and sensitive solid-phase fluorescence immunoassay was employed to determine whether IgG, IgA and IgM RF were detectable in sera from patients with various types of glomerulonephritis, rheumatoid arthritis (RA) and those with various streptococcal infections. IgG, IgA and IgM RF were significantly increased in the majority of patients with RA, lupus nephritis (SLE), acute poststreptococcal glomerulonephritis (APSGN) and various streptococcal infections. The titers of IgG and IgA RF were significantly higher in patients with APSGN than in those with simple pharyngitis. IgM RF was increated in patients with IgA nephropathy (IgA-N) and in those with membranoproliferative glomerulonephritis type I (MPGN). No significantly high RF was observed in membranous nephropathy (MN) or chronic mesangial proliferative glomerulonephritis without IgA deposition (PGN). It is suggested that some autologous immune mechanisms may be involved in the pathogenesis of some types of glomerulonephritis.     

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。     

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.     

Pathogenesis of poststreptococcal glomerulonephritis a century after Clemens von Pirquet

Considerable insight has been gained into the etiopathogenesis of poststreptococcal glomerulonephritis since the landmark theoretical construct of Clemens von Pirquet postulated that disease-causing immune complexes were responsible for the nephritis that followed scarlet fever. Over the years, molecular mimicry between streptococcal products and renal components, autoimmune reactivity and several streptococcal antigens have been extensively studied. Recent investigations assign a critical role to both in situ formation and deposition of circulating immune complexes that would trigger a variety of effector mechanisms. Glomerular plasmin-binding activity of streptococcal glyceraldehyde-3-phosphate-dehydrogenase may play a role in nephritogenicity and streptococcal pyrogenic exotoxin B and its zymogen precursor may be the long-sought nephritogenic antigen.     

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.     

Rare immune-mediated pneumonitis in association with post-streptococcal glomerulonephritis

We describe the case of a 48-year-old man with an acute nephritis and respiratory failure. Clinical history, streptococcal antibody titres and renal biopsy led to a diagnosis of post-streptococcal glomerulonephritis. Respiratory investigations excluded pulmonary oedema and infection. We hypothesize that this man had a co-existing post-streptococcal glomerulonephritis and an immune-mediated pneumonitis. This is a very rare association, which was last described in 1982.     

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.     

Vasectomy: Study of Circulating Immune-Complexes and its Correlation with Antisperm Immunity in Man, with a Twelve-Month Follow-up Study

Circulating immune-complexes (CIC) have been detected in sera of vasectomized subjects using the Clq Binding Assay. Results seem to indicate that CIC are a feature of the early post-operative period and a consequence of acute immunization against sperm antigens. The progressive disappearance of CIC from the third month after vasectomy with the simultaneous increase in antisperm antibody percentage and titre suggests that CIC could be a temporary feature in vasectomized men and do not lead to a chronic disease, related to a Type III immune reaction.     

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.     

Reduction in Platelet-Binding Immunoglobulins and Improvement in Platelet Counts in Patients with HIV-Associated Idiopathic Thrombocytopenia Purpura (ITP) Following Extracorporeal Immunoadsorption of Plasma Over Staphylococcal Protein A-Silica

Platelet-directed antibodies and circulating immune complexes (CIC) were removed from plasma of patients with human immunodeficiency virus (HIV) infection and idiopathic thrombocytopenic purpura (ITP) by extracorporeal immunoadsorption using columns of Staphylococcal protein A-silica (Prosorba columns). In addition, stimulation of a broadly cross-reactive anti-F(ab')2 antibody response was observed. These antibodies also appeared to play a role in the additional removal of platelet-directed immunoglobulins (Igs) and CIC from plasma. Removal of these components from plasma was associated with diminishing levels of antibodies and CIC on patient platelets and significant increases in platelet counts. Extracorporeal immunoadsorption of IgG and CIC from plasma is a beneficial new treatment modality for HIV-associated ITP.