Renal Disease in Autoimmune Strains of Mice1

Howie, J. B.; Helyer, B. J.; Casey, T. P.; Aarons, I

doi:10.1159/000390024

Cited by 3 publications

(5 citation statements)

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“…It has long been appreciated that autoantibodies precede clinical manifestations. For example, in both NZB and NZB/NZW mice the clinical manifestations of Coombs positive autoantibodies and antinuclear autoantibodies (of a number of specificities) precede evidence of, respectively, haemolytic anaemia and lupus nephritis by a few months [22,23]. These murine findings demonstrate a much shorter time interval than observed in the lupus patients reported herein.…”

Section: Discussionsupporting

confidence: 48%

Development of Anti‐dsDNA Autoantibodies Prior to Clinical Diagnosis of Systemic Lupus Erythematosus

et al. 2001

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Anti‐double stranded (dsDNA) antibodies are of considerable diagnostic value and are thought to be involved in the pathogenesis of systemic lupus erythematosus (SLE). Fluctuations in anti‐dsDNA antibody levels are also used as markers for disease activity and exacerbations. In this study we sought to evaluate the anti‐dsDNA antibody level in serum samples collected before the onset of SLE diagnosis. A total of 130 SLE patients were identified with stored serum samples available prior to diagnosis within the US Department of Defense serum repository. All 633 sera available from these patients were screened for anti‐dsDNA antibodies using an enzyme linked immunosorbant assay (ELISA). Within this cohort 55% of cases had detectable anti‐dsDNA antibodies prior to SLE diagnosis. The onset of anti‐dsDNA antibodies ranged from 9.3 years before to within the same month as diagnosis (with a mean onset 2.7 years before diagnosis). In order to assess for fluctuations in anti‐dsDNA levels relative to diagnosis, cases were selected with at least two positive samples, one within 6 months and a second greater than 6 months prior to diagnosis (n = 26). Seven of these cases also had samples available shortly after diagnosis (≤ 6 months) for comparison. Fifty‐eight percent of the 26 cases developed a significant rise in anti‐dsDNA antibody levels within 6 months of diagnosis. A significant decline in anti‐dsDNA levels ensued after diagnosis (and following treatment with corticosteroids) in all seven cases with samples available. Patients with a significant rise in anti‐dsDNA antibodies at diagnosis were more likely to have renal disease than those who did not (66.7% compared to 27.3%, χ2=3.94, P<0.05). These data suggest that anti‐dsDNA antibodies are present in SLE patient sera much earlier than previously suspected. In addition, the data are consistent with increases in anti‐dsDNA levels contributing to the onset of clinical illness in some patients with SLE.

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Section: Discussionsupporting

confidence: 48%

Development of Anti‐dsDNA Autoantibodies Prior to Clinical Diagnosis of Systemic Lupus Erythematosus

et al. 2001

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“…I n the final experiment mice were separated not on the basis of age but on the basis of degree of proteinuria. A reliable correlation between significant proteinuria and survival in untreated female NZB/W mice was reported (13,14) and has been confirmed by us (unpublished observations). In unpublished studies it was further found that the development of 3+ or 4f proteinuria is associated with histologically severe glomerulonephritis.…”

Section: Methodssupporting

confidence: 74%

“…Treated and control mice were housed in the same area and allowed food and water ad libitum. Only female mice were used in these studies because of sex differences in incidence and severity of NZB/W disease (13)(14)(15)(16) and the response to therapy (6,7).…”

Section: Methodsmentioning

confidence: 99%

Therapeutic studies in NZB/W MICE

Steinberg

Gelfand

Hardin

et al. 1975

Arthritis & Rheumatism

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Female NZB/W mice develop a disease closely resembling human systemic lupus and serve as an animal model for therapeutic studies. Several previous studies have demonstrated the efficacy of different immunosuppressive drug regimens in the therapy of glomerulonephritis in NZB/W mice. After the onset of immune complex deposition, treatment with intermittent high doses of cyclophosphamide or daily low doses of the combination of cyclophosphamide, azathioprine, and methylprednisolone has been effective. The present study was designed to compare such effective regimens in mice early in the course of their

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“…The New Zealand Black/New Zealand White F1 (B/W)1 hybrid mouse is an excellent animal model for the study of human systemic lupus erythematosus (1,2). These mice develop a number of immunologic abnormalities, e.g., anti-DNA and antinuclear antibodies (ANA) and hypergammaglobulinemia.…”

Section: Introductionmentioning

confidence: 99%

“…The progression of the skin and kidney immune deposits have been correlated (4). The maximal degree of severity of glomerulonephritis (GN) is attained at 9 mo of age and causes death of most animals by 12 mo of age (1,2,5).…”

Section: Introductionmentioning

confidence: 99%