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Selective blockade of BAFF prevents and treats SLE nephritis in NZM2410 mice

November 10, 2009

To determine whether BAFF or combined BAFF/APRIL blockade is effective in a
mouse model of SLE nephritis characterized by rapidly progressive glomerulosclerosis.
Methods: NZM2410 mice at early and late stages of disease were treated with a short course of
BAFF-R-Ig or TACI-Ig. Mice were followed for proteinuria and serologic profile every two
weeks. Immunohistochemical, flow cytometric and ELISpot analyses of spleens, kidneys and
bone marrows was performed after 8 weeks and after 33 weeks.

A short course of selective blockade of BAFF alone was sufficient to prevent and treat
SLE nephritis in NZM2410 mice despite the formation of pathogenic autoantibodies. Decreases
in spleen size and B cell depletion persisted for more than 33 weeks after treatment and resulted
in secondary decreases in CD4 memory T cell formation and activation of splenic and peripheral
monocytes. Immune complex deposition in the kidneys was dissociated from renal damage and
from activation of renal endothelial and resident dendritic cells.

Selective blockade of BAFF alone resulting in B cell depletion and splenic
collapse was sufficient to prevent and treat disease in this model of non-inflammatory SLE
nephritis. This shows that the inflammatory microenvironment may be a determinant of the
outcome of B cell modulation strategies.

Systemic lupus erythematosus (SLE) is an autoimmune disorder in which loss of
tolerance to nucleic acids is associated with the development of pathogenic autoantibodies that
damage target organs. Lupus nephritis develops in up to 60% of adult SLE patients and is even
more common in children. Induction of remission of lupus nephritis requires the use of potent
immunosuppressive treatment with significant adverse effects, and frequent relapses (1).

...
 
Read the full article here
 
Source lupusresearch.org


Selective blockade of BAFF prevents and treats SLE nephritis in NZM2410 mice

November 10, 2009

To determine whether BAFF or combined BAFF/APRIL blockade is effective in a
mouse model of SLE nephritis characterized by rapidly progressive glomerulosclerosis.
Methods: NZM2410 mice at early and late stages of disease were treated with a short course of
BAFF-R-Ig or TACI-Ig. Mice were followed for proteinuria and serologic profile every two
weeks. Immunohistochemical, flow cytometric and ELISpot analyses of spleens, kidneys and
bone marrows was performed after 8 weeks and after 33 weeks.

A short course of selective blockade of BAFF alone was sufficient to prevent and treat
SLE nephritis in NZM2410 mice despite the formation of pathogenic autoantibodies. Decreases
in spleen size and B cell depletion persisted for more than 33 weeks after treatment and resulted
in secondary decreases in CD4 memory T cell formation and activation of splenic and peripheral
monocytes. Immune complex deposition in the kidneys was dissociated from renal damage and
from activation of renal endothelial and resident dendritic cells.

Selective blockade of BAFF alone resulting in B cell depletion and splenic
collapse was sufficient to prevent and treat disease in this model of non-inflammatory SLE
nephritis. This shows that the inflammatory microenvironment may be a determinant of the
outcome of B cell modulation strategies.

Systemic lupus erythematosus (SLE) is an autoimmune disorder in which loss of
tolerance to nucleic acids is associated with the development of pathogenic autoantibodies that
damage target organs. Lupus nephritis develops in up to 60% of adult SLE patients and is even
more common in children. Induction of remission of lupus nephritis requires the use of potent
immunosuppressive treatment with significant adverse effects, and frequent relapses (1).

...
 
Read the full article here
 
Source lupusresearch.org



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