To study the specificity of gut hyperpermeability in primary glomerulonephritis, we investigated intestinal permeability by means of ⁵¹Cr-EDTA testing in 20 healthy individuals and in 30 patients with Immunoglobulin A nephropathy (IgA GN), 25 with idiopathic nephrotic syndrome (INS) and 20 with immune complex glomerulonephritis (IC-GN; membranous + membranoproliferative glomerulonephritis). Gut permeability was statistically increased in each patient group versus the controls [controls: 2% (0.4-3.9); IgA GN: 3.25% (0.7-17.70); INS: 3.71% (0.82-10); IC-GN: 3.40% (0.30-16); results are median (range); p < 0.005, nonparametric Mann-Whitney test]. An increase in intestinal permeability exceeding the upper limit of control values (95th percentile) was observed in 36% of IgA GN, 60% of INS and 50% of IC-GN patients. We conclude that intestinal permeability is frequently increased in primary glomerulonephritis and may also be increased in types of glomerulonephritis other than IgA GN.

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Using synthetic polyribonucleotides templates as models, the problems of attachment or detachment of DNA dependent‐RNA polymerase to its template have been investigated. In addition, the hypothesis that sites of initiation or termination of transcription might be determined by some specific base sequences was tested with these models. In order to allow a distinction between the transcription process and its first step, which is the binding of the enzyme to its template, the inhibition by different polyribonucletides of the transcription of DNA was examined. A wide range of relative effects was found (Fig. 3). It is remarkable that the polyribonucleotides Poly G and Poly I showing the highest affinities for the enzyme, as well as the homopolymer pair Poly (G + C) of low affinity could not be transcribed into their complementary sequences when used as template. When using the polyribonucleotides as template instead of DNA, the Km for triphosphate binding is about 30 fold higher. It was shwon in inhibition experiments that for a given system, a polyribonucleotide was more efficient as an inhibitor as the concentration of its complementary triphosphate was increased (Fig. 4): this result shows that the triphosphate contributes to the stability of the polyribonucleotide‐enzyme complex. The properties of Poly I or Poly G of having very high affinity for RNA polymerase and of not being transcribed could be used to trap the enzyme not bound to its template at any time before or during the transcription process. Preliminary results are reported in Fig.5. The fact that Poly (G + C) has barely detectable affinity for RNA polymerase can explain the kinetic results obtained when Poly C is used as a template; the G/C ratio reaches one at the end of the reaction and no further incorporation of GMP is observed when enzyme or GTP is added. Only the addition of Poly C can allow resumption of incorporation of the complementary nucleotides (Fig.2A). Consistent with these results is the observation that the enzyme and the product of the reaction migrate separately in a sucrose gradient centrifugation. Our studies show that the relative affinity of RNA polymerase for different homopolymer pairs Poly (A + U), Poly (G + C) is dependent on the nature of the bases involved in these ordered double helical structures.

IgA specific for 7 food and 6 airborne antigens were sought in the serum of 30 adult patients with IgA mesangial nephropathy (IgA GN), 23 with membranous nephropathy (MGN), 20 with idiopathic nephrotic syndrome (INS), 11 with membranoproliferative GN (MPGN) and 22 healthy controls by means of an enzyme-linked immunoassay. The IgA subclass was determined using monoclonal antibodies. Increased levels of IgA specific for gliadin, bovine serum albumin (BSA), ovalbumin, lysozyme and α-lactalbumin were found in IgA GN, while increased levels of IgA to BSA, ovalbumin, lysozyme and α-lactalbumin were observed in MGN; IgA specific for α-lactalbumin were increased in INS, and MPGN patients had reduced levels of IgA to BSA and increased levels of IgA to β-lactoglobulin and α-lactalbumin. These specific IgA to food antigens were restricted to the IgAl subclass. Patients with IgA GN had significantly increased levels of IgA specific for Dermatophagoides pteronyssinus (DP) and Dactil while the MGN group showed increased levels of IgA specific for DP, feathers, Dactil and mold. INS patients had increased levels of IgA specific for DP, feathers, Dactil, mold and dog hairs, while MPGN patients had increased levels of IgA specific for feathers, Dactil, dog hairs and mold. All these specific IgA to airborne antigens were restricted to the IgA1 subclass. Patients with the four types of primary glomerulonephritis had decreased IgA specific for cat hairs which were of both the IgA1 and IgA2 subclasses. We conclude that anomalies of the IgA repertoire to environmental antigens are also encountered in primary glomerulonephritis other than IgA GN.

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