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Clearing the complexity: immune complexes and their treatment in lupus nephritis.

Toong C, Adelstein S, Phan TG - Int J Nephrol Renovasc Dis (2011)

Bottom Line: Deposition of immune complexes in the kidney results in glomerular damage and occurs in all forms of lupus nephritis.The development of nephritis carries a poor prognosis and high risk of developing end-stage renal failure despite recent therapeutic advances.Here we review the role of DNA-anti-DNA immune complexes in the pathogenesis of lupus nephritis and possible new treatment strategies aimed at their control.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Immunology, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, Australia;

ABSTRACT
Systemic lupus erythematosus (SLE) is a classic antibody-mediated systemic autoimmune disease characterised by the development of autoantibodies to ubiquitous self-antigens (such as antinuclear antibodies and antidouble-stranded DNA antibodies) and widespread deposition of immune complexes in affected tissues. Deposition of immune complexes in the kidney results in glomerular damage and occurs in all forms of lupus nephritis. The development of nephritis carries a poor prognosis and high risk of developing end-stage renal failure despite recent therapeutic advances. Here we review the role of DNA-anti-DNA immune complexes in the pathogenesis of lupus nephritis and possible new treatment strategies aimed at their control.

No MeSH data available.


Related in: MedlinePlus

Model of DNA-anti-DNA immune complex generation and glomerular damage in lupus nephritis and potential therapeutic targets.Abbreviations: Abs, antibodies; DCs, dendritic cells; GC, germinal center; ICs, immune complexes; RBCs, red blood cells; RES, reticuloendothelial system.
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f1-ijnrd-4-017: Model of DNA-anti-DNA immune complex generation and glomerular damage in lupus nephritis and potential therapeutic targets.Abbreviations: Abs, antibodies; DCs, dendritic cells; GC, germinal center; ICs, immune complexes; RBCs, red blood cells; RES, reticuloendothelial system.

Mentions: Systemic lupus erythematosus (SLE) is a complex, heterogeneous disease of multi-factorial etiology where multiple genetic, environmental and sex hormonal influences converge to break down B cell tolerance to self-antigens normally sequestered inside the cell nucleus.1 Recent insights obtained from genetic mouse models and genome-wide association scans in large patient cohorts have enabled the identification of several key players in the multistep pathogenesis of lupus (Figure 1). These studies reveal a positive feedback loop whereby inefficient clearance of apoptotic blebs by macrophages results in positive selection of germinal center B cells, which have self-reactivity against nuclear antigens exposed on these blebs. These self-reactive B cells undergo T cell-dependent affinity maturation and isotype switching,2 and differentiate into long-lived plasma cells which reside in the bone marrow. The high affinity IgG anti-DNA antibodies secreted by these cells bind to the DNA to form immune complexes which activate plasmacytoid dendritic cells (pDCs) via toll-like receptor- (TLR-) 9 to produce inflammatory cytokines such as interferon-alpha. These cytokines augment the humoral immune response and lead to further autoantibody production. The high levels of circulating DNA-anti-DNA immune complexes overwhelm the capacity of the reticuloendothelial system (RES) to clear them, and they are deposited in various tissues including glomeruli where local complement activation results in glomerular injury.3


Clearing the complexity: immune complexes and their treatment in lupus nephritis.

Toong C, Adelstein S, Phan TG - Int J Nephrol Renovasc Dis (2011)

Model of DNA-anti-DNA immune complex generation and glomerular damage in lupus nephritis and potential therapeutic targets.Abbreviations: Abs, antibodies; DCs, dendritic cells; GC, germinal center; ICs, immune complexes; RBCs, red blood cells; RES, reticuloendothelial system.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3108794&req=5

f1-ijnrd-4-017: Model of DNA-anti-DNA immune complex generation and glomerular damage in lupus nephritis and potential therapeutic targets.Abbreviations: Abs, antibodies; DCs, dendritic cells; GC, germinal center; ICs, immune complexes; RBCs, red blood cells; RES, reticuloendothelial system.
Mentions: Systemic lupus erythematosus (SLE) is a complex, heterogeneous disease of multi-factorial etiology where multiple genetic, environmental and sex hormonal influences converge to break down B cell tolerance to self-antigens normally sequestered inside the cell nucleus.1 Recent insights obtained from genetic mouse models and genome-wide association scans in large patient cohorts have enabled the identification of several key players in the multistep pathogenesis of lupus (Figure 1). These studies reveal a positive feedback loop whereby inefficient clearance of apoptotic blebs by macrophages results in positive selection of germinal center B cells, which have self-reactivity against nuclear antigens exposed on these blebs. These self-reactive B cells undergo T cell-dependent affinity maturation and isotype switching,2 and differentiate into long-lived plasma cells which reside in the bone marrow. The high affinity IgG anti-DNA antibodies secreted by these cells bind to the DNA to form immune complexes which activate plasmacytoid dendritic cells (pDCs) via toll-like receptor- (TLR-) 9 to produce inflammatory cytokines such as interferon-alpha. These cytokines augment the humoral immune response and lead to further autoantibody production. The high levels of circulating DNA-anti-DNA immune complexes overwhelm the capacity of the reticuloendothelial system (RES) to clear them, and they are deposited in various tissues including glomeruli where local complement activation results in glomerular injury.3

Bottom Line: Deposition of immune complexes in the kidney results in glomerular damage and occurs in all forms of lupus nephritis.The development of nephritis carries a poor prognosis and high risk of developing end-stage renal failure despite recent therapeutic advances.Here we review the role of DNA-anti-DNA immune complexes in the pathogenesis of lupus nephritis and possible new treatment strategies aimed at their control.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Immunology, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, Australia;

ABSTRACT
Systemic lupus erythematosus (SLE) is a classic antibody-mediated systemic autoimmune disease characterised by the development of autoantibodies to ubiquitous self-antigens (such as antinuclear antibodies and antidouble-stranded DNA antibodies) and widespread deposition of immune complexes in affected tissues. Deposition of immune complexes in the kidney results in glomerular damage and occurs in all forms of lupus nephritis. The development of nephritis carries a poor prognosis and high risk of developing end-stage renal failure despite recent therapeutic advances. Here we review the role of DNA-anti-DNA immune complexes in the pathogenesis of lupus nephritis and possible new treatment strategies aimed at their control.

No MeSH data available.


Related in: MedlinePlus