Anti-tumor necrosis factor α treatment of interferon-α-induced murine lupus nephritis reduces the renal macrophage response but does not alter glomerular immune complex formation.

Objective: To analyze the mechanism for the therapeutic effects of tumor necrosis factor α (TNFα) inhibition in a murine model of systemic lupus erythematosus.

Methods: We used the (NZB × NZW)F(1) (NZB/NZW) mouse model of interferon-α-induced lupus nephritis and treated mice with TNF receptor type II (TNFRII) Ig after TNFα expression was detected in the kidneys. Autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA), and autoantibody- forming cells were determined using an enzyme-linked immunospot assay.

Selective blockade of BAFF for the prevention and treatment of systemic lupus erythematosus nephritis in NZM2410 mice.

Objective: To determine whether BAFF or combined BAFF/APRIL blockade is effective in a mouse model of systemic lupus erythematosus (SLE) nephritis characterized by rapidly progressive glomerulosclerosis.

Methods: NZM2410 mice at early and late stages of SLE nephritis were treated with a short course of BAFF-R-Ig or TACI-Ig fusion protein. Proteinuria and serologic profile were evaluated every 2 weeks.

Interferon-alpha treatment of female (NZW x BXSB)F(1) mice mimics some but not all features associated with the Yaa mutation.

Objective: Male (NZW x BXSB)F(1) mice develop antiphospholipid syndrome (APS) and proliferative glomerulonephritis that is markedly accelerated by the Yaa locus encoding an extra copy of Tlr7. Female (NZW x BXSB)F(1) mice with only 1 active copy of Tlr7 develop late-onset glomerulonephritis but not APS. Because a major function of Toll-like receptor 7 is to induce type I interferons (IFNs), our goal was to determine whether IFNalpha can induce or accelerate the manifestations of systemic lupus erythematosus (SLE) in female (NZW x BXSB)F(1) mice.

Prevention of murine antiphospholipid syndrome by BAFF blockade.

Objective: This study was undertaken to determine whether BAFF blockade can be used to prevent or treat antiphospholipid syndrome in a mouse model.

Methods: Eight- and 12-week-old (NZW x BXSB)F(1) mice were treated with BAFF-R-Ig or TACI-Ig alone or in addition to a short course of CTLA-4Ig. Mice were monitored for thrombocytopenia and proteinuria.

Activated renal macrophages are markers of disease onset and disease remission in lupus nephritis.

Costimulatory blockade with CTLA4Ig and anti-CD40L along with a single dose of cyclophosphamide induces remission of systemic lupus erythematosus nephritis in NZB/W F(1) mice. To understand the mechanisms for remission and for impending relapse, we examined the expression profiles of 61 inflammatory molecules in the perfused kidneys of treated mice and untreated mice at different stages of disease. Further studies using flow cytometry and immunohistochemistry allowed us to determine the cellular origins of several key markers.

Similarities and differences between selective and nonselective BAFF blockade in murine SLE.

B cells have multiple roles in immune activation and inflammation separate from their capacity to produce antibodies. B cell depletion is currently under intense investigation as a therapeutic strategy for autoimmune diseases. The TNF family members B cell-activating factor of the TNF family (BAFF) and its homolog A proliferation-inducing ligand (APRIL) are B cell survival and differentiation factors and are therefore rational therapeutic targets.