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Rapidly progressive IgA nephropathy: a form of vasculitis or a complement-mediated disease?

Rojas-Rivera J, Fernández-Juárez G, Praga M - Clin Kidney J (2015)

Bottom Line: In this issue, two clinical studies of crescentic IgAN are presented.The second is a case report showing the effect of eculizumab, a humanized monoclonal antibody that is a terminal cascade complement inhibitor, as salvage therapy for crescentic IgAN resistant to conventional immunosuppression.Both studies broaden our approach to patients with aggressive forms of IgAN.

View Article: PubMed Central - PubMed

Affiliation: Spanish Study Group of Glomerular Disease (GLOSEN) , Hospital Universitario Fundación Jiménez Díaz , Madrid , Spain.

ABSTRACT
A rapidly progressive and crescentic IgA nephropathy (IgAN) is uncommon, but it has a high risk of progression to end-stage renal disease and variable response to immunosuppression. The importance of a positive anti-neutrophil cytoplasmic antibody (ANCA) serology in this group of patients is not fully understood but may have prognostic significance. On the other hand, there is growing evidence of the role of complement in the pathogenesis of IgAN, especially in cases of crescentic IgAN. Therapies directed against the complement system are a potential and rational therapeutic approach. In this issue, two clinical studies of crescentic IgAN are presented. The first work, is a retrospective case-control study describing clinical presentation, histological findings and response to treatment of crescentic IgAN/positive ANCA patients, comparing them with IgAN/negative ANCA patients and ANCA vasculitis patients. The second is a case report showing the effect of eculizumab, a humanized monoclonal antibody that is a terminal cascade complement inhibitor, as salvage therapy for crescentic IgAN resistant to conventional immunosuppression. Both studies broaden our approach to patients with aggressive forms of IgAN.

No MeSH data available.


Related in: MedlinePlus

Main pathogenic mechanisms involved in renal damage in IgA nephropathy. IgA, immunoglobulin A; IC, immune complex; PR3, proteinase-3; MPO, myeloperoxidase.
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SFV095F1: Main pathogenic mechanisms involved in renal damage in IgA nephropathy. IgA, immunoglobulin A; IC, immune complex; PR3, proteinase-3; MPO, myeloperoxidase.

Mentions: Recent findings strongly indicate that the complement system has a deep pathogenic influence in IgAN. Studies of genetic susceptibility have described loci that predispose to IgAN, as well as mutations and polymorphisms in genes encoding factor H and factor H–related proteins. Some of these polymorphisms appear to be protective for the development of IgAN [18–20]. Serum levels of C3 are usually normal or slightly decreased in most patients, but deposits of C3 and C4d are found in a substantial proportion of cases, suggesting that the alternative and the mannose–lectin pathways are activated in IgAN [21]. Deposits of C4d in mesangium [22] and C3d in peritubular cells [23] have been associated with a more aggressive form of the disease. Studies in the Japanese population have found that a serum IgA:C3 ratio >3:1 or 4:1 or high serum levels of C4 binding protein could have an impact on prognosis [24, 25]. Toxic and pro-inflammatory substances released by red blood cells in the tubular lumen during gross haematuria episodes activate the complement system, further aggravating tubulointerstitial damage [26, 27]. Taken together, these findings strongly support a role for complement activation in the pathogenesis and progression of IgAN. Figure 1 summarizes the main pathogenic mechanisms involved in renal damage in IgAN.Fig. 1.


Rapidly progressive IgA nephropathy: a form of vasculitis or a complement-mediated disease?

Rojas-Rivera J, Fernández-Juárez G, Praga M - Clin Kidney J (2015)

Main pathogenic mechanisms involved in renal damage in IgA nephropathy. IgA, immunoglobulin A; IC, immune complex; PR3, proteinase-3; MPO, myeloperoxidase.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581398&req=5

SFV095F1: Main pathogenic mechanisms involved in renal damage in IgA nephropathy. IgA, immunoglobulin A; IC, immune complex; PR3, proteinase-3; MPO, myeloperoxidase.
Mentions: Recent findings strongly indicate that the complement system has a deep pathogenic influence in IgAN. Studies of genetic susceptibility have described loci that predispose to IgAN, as well as mutations and polymorphisms in genes encoding factor H and factor H–related proteins. Some of these polymorphisms appear to be protective for the development of IgAN [18–20]. Serum levels of C3 are usually normal or slightly decreased in most patients, but deposits of C3 and C4d are found in a substantial proportion of cases, suggesting that the alternative and the mannose–lectin pathways are activated in IgAN [21]. Deposits of C4d in mesangium [22] and C3d in peritubular cells [23] have been associated with a more aggressive form of the disease. Studies in the Japanese population have found that a serum IgA:C3 ratio >3:1 or 4:1 or high serum levels of C4 binding protein could have an impact on prognosis [24, 25]. Toxic and pro-inflammatory substances released by red blood cells in the tubular lumen during gross haematuria episodes activate the complement system, further aggravating tubulointerstitial damage [26, 27]. Taken together, these findings strongly support a role for complement activation in the pathogenesis and progression of IgAN. Figure 1 summarizes the main pathogenic mechanisms involved in renal damage in IgAN.Fig. 1.

Bottom Line: In this issue, two clinical studies of crescentic IgAN are presented.The second is a case report showing the effect of eculizumab, a humanized monoclonal antibody that is a terminal cascade complement inhibitor, as salvage therapy for crescentic IgAN resistant to conventional immunosuppression.Both studies broaden our approach to patients with aggressive forms of IgAN.

View Article: PubMed Central - PubMed

Affiliation: Spanish Study Group of Glomerular Disease (GLOSEN) , Hospital Universitario Fundación Jiménez Díaz , Madrid , Spain.

ABSTRACT
A rapidly progressive and crescentic IgA nephropathy (IgAN) is uncommon, but it has a high risk of progression to end-stage renal disease and variable response to immunosuppression. The importance of a positive anti-neutrophil cytoplasmic antibody (ANCA) serology in this group of patients is not fully understood but may have prognostic significance. On the other hand, there is growing evidence of the role of complement in the pathogenesis of IgAN, especially in cases of crescentic IgAN. Therapies directed against the complement system are a potential and rational therapeutic approach. In this issue, two clinical studies of crescentic IgAN are presented. The first work, is a retrospective case-control study describing clinical presentation, histological findings and response to treatment of crescentic IgAN/positive ANCA patients, comparing them with IgAN/negative ANCA patients and ANCA vasculitis patients. The second is a case report showing the effect of eculizumab, a humanized monoclonal antibody that is a terminal cascade complement inhibitor, as salvage therapy for crescentic IgAN resistant to conventional immunosuppression. Both studies broaden our approach to patients with aggressive forms of IgAN.

No MeSH data available.


Related in: MedlinePlus