Chronical administration of anti-DNA antibodies by subcutaneous injection of hybridoma clones in BALB/c and NZBxNZW/F1 mice. Experimental model of the pathogenic role of DNA in acute lupus disease.

Several sets of data suggest that specific classes of anti-DNA antibodies could be implicated in the genesis of glomerular lesions in SLE. The goal of this work is to investigate if this pathogenic role could be related to the antibodies' genetic origin--from BALB/c or NZBxNZW/F1 mice--or to their physiological origin--induced either by DNA or by polyclonal B cell activation in normal mice. For this purpose, anti-DNA antibody hybridoma clones produced from different origins were subcutaneously injected in BALB/c or NZBxNZW/F1 female mice, followed by studies of immunological parameters and kidney lesions. Results concur that the induced anti-DNA antibodies can play a role in fatal disease development, related to clonal specificity but not to the way of stimulation which was either polyclonal B cell activation or DNA immunization. Also, they emphasize the possible very lethal role of serum circulating DNA.

Rapidly progressive glomerulonephritis associated with amyloidosis: efficacy of plasma exchange.

This report describes one case of rapidly progressive glomerulonephritis associated with amyloidosis in a 53-year-old woman with rheumatoid arthritis, successfully treated with intensive plasma exchange and immunosuppression. Amyloid deposits were present in all of 20 glomeruli in the kidney biopsy specimen and eight out of nine nonfibrosed glomeruli contained crescents. With intensive plasma exchange and immunosuppressive drugs, renal function improved, and hemodialysis was discontinued. After 2 years, renal function was stable at a moderate level of impairment, but heavy proteinuria persisted.

[Hypothesis: immune complex glomerulonephritis and auto-immunity (author's transl)]. / Glomérulonéphrite à complexes immuns et auto-immunité.

Experimental studies on the NZBxNZW mouse lupus disease and on the development of immune complex (IC) glomerulonephritis in mouse infected with Escherichia coli lead us to state the following hypothesis: two types of factors are implicated in the development of immune complex glomerulonephritis: 1) specific factors leading to the production of IC involving antigens from the triggering agents; 2) non specific factors leading to the production of IC involving auto-antigens.

Immune complex glomerulonephritis in mice infected with Escherichia coli.

C57Bl/6 mice were injected intraperitoneally with 10(8) to 2 x 10(8) living K 38 Escherichia coli (E. coli) and serological changes and kidney involvement were studied. E. coli were found in the blood 45 min to 24 hr after injection. In serum, large amounts of deoxyribonucleic acid (DNA) were present 24 hr after E. coli injection, and thereafter disappeared. Seven days after infection, antibodies directed against E. coli, anti-DNA antibodies and C1q-binding substances were found in serum and the kinetics of the variations of these parameters were studied until day 35. Kidney lesions were evaluated immunochemically and by optical and electron microscopy. In the glomeruli, heavy granular deposits of IgG and IgM were constantly found in mesangium and along capillary walls. In most kidneys slight granular deposits of IgG and IgM were also found in the tubules. Histological studies revealed in the glomeruli mild endocapillary cell proliferation, focal thickening of glomerular basement membrane and dense deposits in mesangial and subendothelial areas and inside the glomerular basement membrane; in the tubules dense deposits were focally observed inside the tubular basement membrane.

Acceleration of glomerulonephritis in NZB x NZW mice by early immunization with DNA and injection of bacterial lipopolysaccharide. Experimental approach to the treatment of lupus nephritis by use of the accelerated model of NZB x NZW mouse disease.

The effects of early immunization with DNA and of injection of bacterial lipopolysaccharide (LPS) on the glomerulonephritis of NZB x NZW mice were studied. Combined injections of DNA complexed to methylated bovine serum albumin (DNA-mBSA) and of LPS appeared to be more efficient in accelerating the disease in NZB x NZW mice than injections of DNA-mBSA or LPS alone. A rapid increase in levels of anti-DNA antibodies, an early appearance of severe renal lesions and a shortened survival were observed in mice injected with both DNA-mBSA and LPS. This new model was found to be suitable for therapeutic studies in mice with accelerated disease treated with cyclophosphamide and heparin. The efficacy of cyclophosphamide for the treatment of NZB x NZW mouse disease was shown by immunological and histological studies in mice younger than 4 months. Heparin appeared to have a beneficial effect by preventing the endocapillary cellular proliferation induced by injections of DNA-mBSA and LPS. The accelerated model of NZB x NZW mouse disease might be a useful tool for experiments on the treatment of lupus nephritis.

[Lupus nephropathy. Treatment with the indomethacin-hydroxychloroquine combination and comparison with corticoids]. / La néphropathie lupique Traitement par l'association indométacine-hydroxychloroquine et comparaison avec les corticoïdes

The authors report their comparative experience of the treatment of proliferative lupus glomerulonephritis using prednisone (16 patients) or the indomethacin-hydroxychloroquine association (12 patients). Prednisone in high dosage was associated in this series with 9 deaths and in 6 patients, with renal failure or an extra-renal complication. By contrast, the indomethacin-hydroxychloroquine association proved to be highly effective, without side-effect. In the endocapillary glomerulonephritis group (8 cases) the authors obtained 7 durable remissions (36.3 months on average) and 1 temporary remission of 24 months, with an average length of treatment of 45.8 months. In the extracapillary glomerulonephritis group (4 cases) the authors obtained 1 remission, 2 improvements and I death, with an average length of treatment of 16.8 months. This combination has a highly significant anti-proteinuric and anti-haematuric action, with a constant efficiency on renal function and on the extra-renal signs of lupus. Its effect is less constant on the immunological disorders. Study of iterative renal biopsies confirms this favourable impression. According to these results, the authors propose a provisional scheme of management of proliferative lupus glomerulonephritis.