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

Meera Ramanujam, Ramalingam Bethunaickan, Weiqing Huang, Haiou Tao, Michael P. Madaio, Anne Davidson

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

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. Immunohistochemical, flow cytometric, and enzyme-linked immunospot analyses of the spleen, kidney, and bone marrow were performed after 8 weeks and after 33 weeks. Results. 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. Conclusion. Selective blockade of BAFF alone, which resulted in B cell depletion and splenic collapse, was sufficient to prevent and treat the disease in this model of noninflammatory SLE nephritis. This shows that the inflammatory microenvironment may be a determinant of the outcome of B cell modulation strategies.

Original languageEnglish (US)
Pages (from-to)1457-1468
Number of pages12
JournalArthritis and Rheumatism
Volume62
Issue number5
DOIs
StatePublished - May 1 2010

Fingerprint

Lupus Nephritis
Systemic Lupus Erythematosus
Kidney
B-Lymphocytes
Spleen
Antigen-Antibody Complex
Proteinuria
Autoantibodies
Dendritic Cells
Monocytes
Bone Marrow
T-Lymphocytes
Enzymes
Proteins

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

Selective blockade of BAFF for the prevention and treatment of systemic lupus erythematosus nephritis in NZM2410 mice. / Ramanujam, Meera; Bethunaickan, Ramalingam; Huang, Weiqing; Tao, Haiou; Madaio, Michael P.; Davidson, Anne.

In: Arthritis and Rheumatism, Vol. 62, No. 5, 01.05.2010, p. 1457-1468.

Research output: Contribution to journalArticle

Ramanujam, M, Bethunaickan, R, Huang, W, Tao, H, Madaio, MP & Davidson, A 2010, 'Selective blockade of BAFF for the prevention and treatment of systemic lupus erythematosus nephritis in NZM2410 mice', Arthritis and Rheumatism, vol. 62, no. 5, pp. 1457-1468. https://doi.org/10.1002/art.27368
Ramanujam, Meera ; Bethunaickan, Ramalingam ; Huang, Weiqing ; Tao, Haiou ; Madaio, Michael P. ; Davidson, Anne. / Selective blockade of BAFF for the prevention and treatment of systemic lupus erythematosus nephritis in NZM2410 mice. In: Arthritis and Rheumatism. 2010 ; Vol. 62, No. 5. pp. 1457-1468.
@article{f32e00cf983840009cd796ad32c60af7,
title = "Selective blockade of BAFF for the prevention and treatment of systemic lupus erythematosus nephritis in NZM2410 mice",
abstract = "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. Immunohistochemical, flow cytometric, and enzyme-linked immunospot analyses of the spleen, kidney, and bone marrow were performed after 8 weeks and after 33 weeks. Results. 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. Conclusion. Selective blockade of BAFF alone, which resulted in B cell depletion and splenic collapse, was sufficient to prevent and treat the disease in this model of noninflammatory SLE nephritis. This shows that the inflammatory microenvironment may be a determinant of the outcome of B cell modulation strategies.",
author = "Meera Ramanujam and Ramalingam Bethunaickan and Weiqing Huang and Haiou Tao and Madaio, {Michael P.} and Anne Davidson",
year = "2010",
month = "5",
day = "1",
doi = "10.1002/art.27368",
language = "English (US)",
volume = "62",
pages = "1457--1468",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "5",

}

TY - JOUR

T1 - Selective blockade of BAFF for the prevention and treatment of systemic lupus erythematosus nephritis in NZM2410 mice

AU - Ramanujam, Meera

AU - Bethunaickan, Ramalingam

AU - Huang, Weiqing

AU - Tao, Haiou

AU - Madaio, Michael P.

AU - Davidson, Anne

PY - 2010/5/1

Y1 - 2010/5/1

N2 - 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. Immunohistochemical, flow cytometric, and enzyme-linked immunospot analyses of the spleen, kidney, and bone marrow were performed after 8 weeks and after 33 weeks. Results. 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. Conclusion. Selective blockade of BAFF alone, which resulted in B cell depletion and splenic collapse, was sufficient to prevent and treat the disease in this model of noninflammatory SLE nephritis. This shows that the inflammatory microenvironment may be a determinant of the outcome of B cell modulation strategies.

AB - 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. Immunohistochemical, flow cytometric, and enzyme-linked immunospot analyses of the spleen, kidney, and bone marrow were performed after 8 weeks and after 33 weeks. Results. 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. Conclusion. Selective blockade of BAFF alone, which resulted in B cell depletion and splenic collapse, was sufficient to prevent and treat the disease in this model of noninflammatory SLE nephritis. This shows that the inflammatory microenvironment may be a determinant of the outcome of B cell modulation strategies.

UR - http://www.scopus.com/inward/record.url?scp=77951739752&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951739752&partnerID=8YFLogxK

U2 - 10.1002/art.27368

DO - 10.1002/art.27368

M3 - Article

VL - 62

SP - 1457

EP - 1468

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 5

ER -