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To determine the effect of prolonged administration of exogenous interferon on the autoimmune disease of NZB/W female mice, forty-four NZB/W mice received three injections per week of 6.4 × 104 interferon units from birth to 33 weeks, forty mice were injected with mock interferon and forty-eight mice were left untreated. In mice injected with interferon growth was delayed, survival was decreased, and the severity of the glomerulonephritis was enhanced. Interferon increased the titre of serum anti-ssDNA and anti-soluble nucleoprotein antibodies, but had no effect on the circulating immune complex load. These results suggest that interferon in some way affects local deposition of immune complexes within the glomerulus. [ABSTRACT FROM AUTHOR]

Using the Raji cell radioimmune assay, we found low levels of circulating immune complexes (IC) in a small percentage of patients with schistosomiasis and filariasis. C3d levels, measured by immunoprecipitation, were elevated in a large number of these patients, whereas complement levels were within normal limits. Proteinuria was not found in any of the 55 patients studied. Circulating IC or elevated C3d levels were not found in any of the 19 patients with hydatidosis. The increased C3d levels, apparently not related to circulating IC, may be due to direct complement activation by parasite antigens or to sequestered IC. The latter hypothesis appears more attractive because the highest levels of C3d were found in schistosomiasis whereas schistosome antigens were unable to activate complement in vitro.

A case of multiple myeloma with intra- and extracapillary proliferative glomerulonephropathy and other unusual morphologic and clinical manifestations is described. The probable role of light chain proteins in the pathogenesis of the glomerular lesions is discussed. Evidence is presented documenting the beneficial effects of appropriate therapy on the activity and progression of the renal lesions.

Treatment by procyanidolic oligomers can significantly decrease the proteinuria indiced in the Rat by intravenous injection of anti glomerular basement membranes antibodies. Immunohistological analysis shows that procyanidolic oligomers do not interfere with the mechanisms of immunopathological injury involved in this model (antibody binding to glomerular basement membrane, complement activation, glomerular influx of polymorphonuclear leucocytes). Their protective effect may be due to an increased resistance of the glomerular capillary to the inflammatory mediators released by neutrophils.

A 52 year old man was admitted to hospital for persistent back pain, fixed proteinuria of 6g/24 h that lead to the nephrotic syndrome (proteids 40 g/l, albumin 21,2 g/l). Two possible etiologies were envisaged: 1) Myeloma with K light chains as evidenced by biological findings (absence of normal Ig, presence of K light chains both in blood and urine, malignant medullary plasmocytosis) as well as x-rays (small punched out lesions). 2. Diabetes mellitus (blood glucose 2,4 g/l) with retinal and neurological involvement. Percutaneous renal biopsy revealed nodular glomerular sclerosis compatible with both diabetes and myeloma as well as homogeneous refringent thickening of tubular basement membranes more specific of myloma. No amyloid deposits, myelomatous casts were seen and anti-K light chain fixation was negative at immunofluorescence. An evolution of 33 months duration let to chronic renal failure (plasma creatinine 47 mg/l). The respective role of myeloma and diabetes in the genesis of this glomerular nephropathy are discussed.

The relation between the duration of bacterial infection and circulating immune complexes (CIC) level was evaluated using the C1q binding assay in a group of patients with well defined clinical sepsis. Fifty-four patients with endocarditis and 35 with post-open heart surgery mediastinitis were prospectively studied over a period of 2 years. CIC were detected in 42% of patients studied. Interindividual variations were observed but it was found that the level of CIC increased statistically with time (P less than 0.001). CIC were statistically linked with cryoglobulinemia (P less than 0.001), rheumatoid factor (P less than 0.001) and a decreased CH50 (P less than 0.05). CIC were more frequent in patients with endocarditis (53%) than in patients with mediastinitis (24%). However, when the duration of the infection was taken into account the difference was no longer significant. No relation could be evidenced between the incidence of CIC and clinical symptoms including prognosis and renal signs. In our experience, determination of CIC does not have a critical clinical value.

Renal transplantation was performed in five adult patients with thrombotic microangiopathy, three of whom had had a bilateral nephrectomy prior to transplantation. The graft remained functional in three patients 72, 18, and 12 months after transplantation. One patient developed a thrombosis of the renal artery and one patient died from infection. There was no clinical or histological evidence of recurrence of thrombotic microangiopathy in the five patients after transplantation. Immunological investigations were performed in four of five patients before transplantation: C3 and C1q levels were low in two patients; serum C3-splitting activity and circulating immune complexes were present in all four patients and remained unchanged on haemodialysis and/or after bilateral nephrectomy. Complement abnormalities and immune complexes were not detected in the three patients with successful renal transplantation.

Suckling rats were injected for 14 to 17 days with potent rat-cell-culture interferon preparations or various heterologous interferon or control preparations. Only treatment with rat interferon resulted in a delay in growth and maturation of different organs and the subsequent development of an "immune complex" type nephritis. Thus, 38 of 43 rats treated with rat interferon developed a severe glomerulonephritis. Thus, 38 of 43 rats treated with rat interferon developed a severe glomerulonephritis, whereas only 3 of 99 rats in the various control groups had minimal renal lesions. Deposits of IgG and C3 along the glomerular basement membrane were only seen in interferon-treated rats.

Glomerular lesions were studied in 41 patients with hepatic cirrhosis (32 cases) or steatosis (9 cases) by optical microscopy (38 cases) and immunofluorescence (22 cases) examinations of biopsy samples. The most frequently observed lesion on optical microscopy was a glomerulosclerosis (16 cases), arteriolar lesions being present in 15 cases, two-thirds of which had associated glomerular lesions. Immunofluorescence revealed the presence of immunoglobulin deposits in 17 cases, these possessing two main characteristics: the prevalence of IgA (14 cases), alone or in association with other immunoglobulins; and the predilection for the mesangium alone, or in association with parietal deposits. The glomerular nephropathy in the cirrhotic patients was completely latent in 3 out of 4 cases, renal signs, when they existed, being of mild intensity. Renal lesion can occur in the absence of severe hepatopathy, particularly in the presence of steatosis. IgA deposits in the mesangium, a fundamental feature of hepatic glomerulopathy, can be related to the presence of IgA deposits in the liver sinusoids, suggesting the development of IgA deposits in several organs during these affections. Their pathogenesis is still obscure but two hypotheses have been suggested: an immune disease with deposits of circulating immune complexes in the kidney; a non-immune disease, IgA deposits being a secondary and not a primary feature.

A renal biopsy performed on a young woman with proteinuria showed a nephropathy consisting of major interstitial infiltration by lipophages and thickening of the glomerular capillary walls with a large amount of "spikes". Anti-IgG, IgM, C3 and C1q sera bound themselves to the extramembranous deposits and the anti-IgM serum to the endomembranous deposits. This striking finding was associated with a regenerative nodular hyperplasia of the liver, an entity that has been observed in only about 20 cases. An underlying immunological defect was suggested by the continuous presence of a mixed cryoglobulinemia.

30 renal biopsies were performed in 20 adult patients with acute diffuse endocapillary glomerulonephritis. 11 patients who presented with acute renal failure (ARF) and 9 patients who had normal or mildly altered renal function were compared in order to look for clinical or pathologic features peculiar to each group and possible differences in outcome. All patients underwent early renal biopsy, and 8 had repeat biopsies. There were no significant differences in clinical, immunologic or histologic features between the two groups. In repeat biopsies, there were no histologic nor immunohistologic differences between patients with or without initial ARF. After a mean follow-up period of 18 months, the overall clinical outcome appeared favorable and was similar in the two groups. Thus, initial ARF in patients with acute endocapillary glomerulonephritis does not imply a bad prognosis. The recognition of pure endocapillary proliferation in patients with anuric acute glomerulonephritis by means of renal biopsy may avoid unnecessary and potentially hazardous treatment.

(1) AIN is the most frequent pattern of drug-induced immunologically mediated renal injury. A number of drugs may be responsible for AIN, namely methicillin and other penicillin derivatives, rifampicin, phenindione and sulfonamides. Particular clinical and pathological features often suggest an immune pathogenetic mechanism. IgG anti-TBM and IgE antibodies have been found in only a few cases and it is likely that antibody-mediated and cell-mediated injury may operate in the same patient. (2) Only few examples of drug-induced vasculitis and glomerulonephritis are known, and the pathophysiology of this kind of renal damage is poorly understood.

Among 22 cases of drug-induced acute interstitial nephritis (AIN), noncaseating interstitial granulomas were found in eight cases (36%). Acute renal failure (ARF), oliguric in three patients, appeared within 1-20 days after the beginning of therapy. Clinical symptoms suggesting a hypersensitivity reaction were unusual, marked blood eosinophilia was absent, and immunologic tests were inconstantly positive. The discovery of interstitial granulomas may be a clue to the diagnosis of drug-induced AIN, especially when the inflammatory infiltrates do not contain eosinophils. Since significant residual renal impairment may be observed the benefit of early steroid therapy must be debated.