[Editorial review: glomerulonephritis and renal transplantation].
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Biomedical subjects
Publications and source records attributed to G Lagrue.
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A potent monospecific anti-C2 was used for quantitation of serum C2 by rocket immunoelectrophoresis (RIE). This ready procedure was compared to the one-step hemolytic titration utilizing C2-deficient human serum. RIE detected 4 nanograms C2 in 5 microliters samples. Using highly purified C2 as a reference, C2 concentration in pooled normal human sera was estimated around 50 micrograms/ml by both test systems. The reliability of RIE was assessed when immunochemical and hemolytic determinations were comparatively performed in 120 pathological sera. The correlation coefficient was significant (r = 0.69) and only 8 sera were found outside the expected range, exhibiting an abnormally high C2 protein. They were obtained from 6 patients with cryoglobulinemia associated connective tissue disease and 2 with acute glomerulonephritis. These occasional findings suggested the possibility of an activation of C2 hemolytic activity without simultaneous loss of C2 protein. In 16 sera of individuals with familial C2 deficiency (r = 0.83) and 29 sera of patients with angioneurotic edema (r = 0.72), RIE provided an extremely simple and reliable alternative to the time consuming hemolytic titration of C2.
Mortality in familial paroxysmal polyserositis results mainly from renal amylosis, the outcome, until recently, being always fatal. Continuous colchicine administration prevents acute relapses, but certain recent observations have demonstrated that this treatment may be able to prevent the onset of amyloid disease. It could even provoke its regression, at least if administration is during the early stages before the development of renal insufficiency. The mechanism of this preventive action against amyloid disease occurrence is discussed as a function of current knowledge of amyloidogenesis.
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Plasma levels of C3d, which is liberated by enzymatic cleavage of C3, are determined in 97 patients with primitive chronic glomerular nephritis. This level is indicative of an abnormally high consumption of C3. In all cases where C3 is low, C3d is found at abnormally high levels. When the level of C3 is normal, C3d may, however, be elevated: a more subtle interpretation of the pathologic significance of C3 in immune disease is thus possible.
Red cell deformability, which allows cells of 7 mu diameter to flow through capillaries not larger than 3 mu, can be approached by the measure of blood filterability on nuclepore 5 mu filters. Filterability is reduced in arterial diseases. We have, in 72 patients, correlated red cell filterability, with the number of cardiovascular risk factors present high blood pressure, overweight, diabetes, hyperuricemia, hyperlipemia smoking). There is a statistical difference between groups with risk factors present as a whole and with O risk factor (p less than 0.01). The difference is highly significant between O and 4 risk factors (p less than 0.0005). Filterability decrease is also directly correlated with the number of cigarettes smoked per day (less than 0.05) and decrease is enhanced by smoking two cigarettes.
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Measurement of serum C3 does not provide precise informations concerning an eventual consumption of this complement component during an immunological process. An increased synthetic rate may compensate an accelerated catabolism. The study of breakdown products of C3, such as C3d is a more sensitive approach of the role of complement in some immunological disorders. Therefore C3d was measured in the serum of patients with chronic non systemic glomerular diseases. High values of serum C3d were found in all cases of hypocomplementemic glomerulonephritis. Circulating C3d was also increased to a lower extent, in patients with normocomplementemic nephritis such as minimal change disease, mesangial nephritis with IgA deposits and membraneoproliferative (type I) glomerulonephritis. The data suggested the involvement of complement in a number of glomerulonephritis. Participation of complement in immunological disorders particularly in chronic non systemic glomerulonephritis could require a reevaluation when functional tests are performed in addition to static measurements.
A patient with non-systemic idiopathic glomerulonephritis was found to have a complete deficiency of C2, the second component of complement. The clinical course, histological findings and serological abnormalities are reported in detail. The renal disease was a mild glomerulonephritis with mesangial and subendothelial immune deposits comprising IgG, IgM and C3, increased mesangial matrix without significant cell proliferation. An immunogenetic analysis of the patient's family was carried out. It was demonstrated that the homozygous C2 deficiency was associated with heterozygotism for HLA-A, B and D. Only one of the C2 deficient genes was associated with the expected HLA-A10, B18 haplotype and the propositus was HLA-D2 negative. This report confirms the fact that non-systemic glomerulonephritis should be included in the variety of immunological disorders associated with a complement deficient state. However, C2 deficiency does not seem to be related specifically to a given histological variety of glomerulonephritis.
Hereditary angioedema (HANE) is a rare, life-threatening disease due to the deficiency of C1 inhibitor (C1 Inh). Androgen therapy has been recently shown to be effective for prophylaxis of Hane attacks. Since life-long androgen therapy may be hazardous, this study was designed to define the minimal doses required for effectiveness. Ten patients from six different families were treated during cumulative 73 months by danazol and/for methandrostenolone. One tablet/day of either drug was the minimal requirement to prevent any attack in all patients. When 3 tablets/day were given, complement abnormalities were simultaneously rapidly reversed. When 1 tablet/day was given the biological effect was barely detectable, except for C2. Serum C2 levels may, therefore, represent the best criteria of androgen therapy effectiveness. Thus, an excellent clinical result can be obtained with much lower doses of androgens than previously stated. This result seemed important with respect to the serious dose-dependent risk of androgens.
For studies on cathodoluminescence, we equipped a scanning electron microscope with a prism spectrometer and sensitive photomultiplier. The apparatus is described and our initial results are presented on the analyse of cathodoluminescence. The material observed promarily involved studies of immunofluorescent specimens. Humal lymphocytes were labelled with a fluorescent antibody and cryosections of rat kidney with Masugi nephritis were labelled with a fluorescent specific antibody. Our apparatus permitted monochromatic imaging of cathodoluminescence emissions and resulted in much improved micrographs. Some possible improvements of the technique are discussed.