Immunological Studies in Nephritis

Freedman, Paul D.; Markowitz, A. S.

doi:10.1016/s0140-6736(59)90493-3

Cited by 16 publications

(9 citation statements)

References 8 publications

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“…At around the same time it was recognized that immune complexes were likely to play an important pathogenic role in SLE. Dixon et al [8] had shown that immune complexes were responsible for experimental serum sickness, and it was shown as early as 1959 that antinuclear antibodies could be eluted from the glomeruli in the case of lupus nephritis [9]. By 1961, therefore, it was already regarded as entirely plausible that immune complexes involving DNA-containing antigens might be important in SLE [10].…”

Section: Introductionmentioning

confidence: 99%

The treatment of systemic lupus erythematosus (SLE) in NZB/W F1 hybrid mice; studies with recombinant murine DNase and with dexamethasone

Macanović

Sinicropi²,

Shak³

et al. 1996

Clinical and Experimental Immunology

139

107

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SUMMARYThe effects of recombinant mouse DNase on a well established murine model of spontaneous SLE have been evaluated. Daily intraperitoneal injections of DNase were given to female NZB/NZW F 1 mice during the period of disease development from 4 to 7 months of age or at the height of disease activity from the age of 7 months for 3 weeks. This treatment was compared with the injections of diluent and with an immunosuppressive dose of dexamethasone. The effects of treatment were evaluated using the immunological parameters of disease activity (antinucleoprotein antibody, immune complexes, serum immunoglobulins, anti-cardiolipin antibodies), proteinuria, serum creatinine and renal histopathology (light microscopy, immunofluorescence and electron microscopy). The dose of dexamethasone used (1 mg/kg per day from the age of 4 months) was sufficient to suppress the development of lupus entirely. Treatment with DNase starting at the age of 4 months postponed the development of the disease by about 1 month and extended the period from the onset of disease to death by about 30%. Mice treated for 3 weeks during the most active phase of the disease at 7 months of age showed more dramatic effects. Proteinuria and serum creatinine were significantly reduced and renal histopathology was strikingly less severe than in the control group. Immune complexes involving DNA-containing antigens are believed to play a crucial role in the pathogenesis of SLE. DNA-nucleoprotein, even in immune complexes, can be destroyed by DNase. This enzyme therefore provides a rational way to interfere with the disease process. The results reported here encourage a trial of recombinant human DNase in human SLE and lupus nephritis.

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Section: Introductionmentioning

confidence: 99%

The treatment of systemic lupus erythematosus (SLE) in NZB/W F1 hybrid mice; studies with recombinant murine DNase and with dexamethasone

Macanović

Sinicropi²,

Shak³

et al. 1996

Clinical and Experimental Immunology

139

107

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“…Shortly after these observations had been described in a preliminary communication (4), Klein and Burkholder reported independently the localization of complement in the glomeruli in nephrotoxic nephritis in the rat (14).…”

Section: Resultsmentioning

confidence: 82%

Gamma Globulin and Complement in the Diseased Kidney

Freedman¹,

Markowitz²

1962

J. Clin. Invest.

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“…Complement proteins were fi rst detected in the glomeruli of patients with glomerulonephritis more than 50 years ago. 1,2 Th e fi rst complement pathway discovered was the classical pathway, which is primarily activated by antibody bound to antigen. Early studies on the function of complement identifi ed it as a heat-labile system that complemented the function of immunoglobulin, and the system was termed ' complement ' because it was believed to play a complementary (that is, secondary) role in the elimination of bacteria by antibodies.…”

mentioning

confidence: 99%

“…In severe lupus nephritis, as in other forms of rapidly progressive glomerulonephritis, CD4 + T cells are present within glomeruli. 1 Given this complex and diverse eff ector involvement, a better understanding of eff ector responses in severe lupus nephritis is important for making progress in treatments for this disease. Over the years, much eff ort has been focused on the role of immunoglobulin and humoral mediators in defining pathogenic effector mechanisms of glome rulonephritis.…”

mentioning

confidence: 99%

Factor friction: protective and pathogenic roles for complement factors in immune complex glomerulonephritis

Thurman

2012

Kidney International

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The classical pathway of complement is activated in patients with immune complex glomerulonephritis. However, Alexander et al. demonstrate that factor H, an alternative pathway regulator, is critical for protecting mice from immune-complex-mediated glomerular injury. In mice that lack factor H, signaling through the C5a receptor is necessary for the development of injury. These results suggest that factor H may be critical for limiting injury in a wide range of autoimmune and inflammatory renal diseases.

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Immunological Studies in Nephritis

Cited by 16 publications

References 8 publications

The treatment of systemic lupus erythematosus (SLE) in NZB/W F1 hybrid mice; studies with recombinant murine DNase and with dexamethasone

The treatment of systemic lupus erythematosus (SLE) in NZB/W F1 hybrid mice; studies with recombinant murine DNase and with dexamethasone

Gamma Globulin and Complement in the Diseased Kidney

Factor friction: protective and pathogenic roles for complement factors in immune complex glomerulonephritis

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