Immunologic Changes Implicated in the Pathogenesis of Focal Segmental Glomerulosclerosis
Focal segmental glomerulosclerosis is a histological pattern on renal biopsy caused by diverse mechanisms. In its primary form, a circulatory factor is implicated in disease onset and recurrence. The natural history of primary FSGS is unpredictable, since some patients are unresponsive towards immun...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2016-01-01
|
Series: | BioMed Research International |
Online Access: | http://dx.doi.org/10.1155/2016/2150451 |
id |
doaj-2b3bc19e33f8440288c13ef9090cc4d7 |
---|---|
record_format |
Article |
spelling |
doaj-2b3bc19e33f8440288c13ef9090cc4d72020-11-25T00:11:36ZengHindawi LimitedBioMed Research International2314-61332314-61412016-01-01201610.1155/2016/21504512150451Immunologic Changes Implicated in the Pathogenesis of Focal Segmental GlomerulosclerosisAndreas Kronbichler0Johannes Leierer1Jun Oh2Björn Meijers3Jae Il Shin4Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Anichstraße 35, 6020 Innsbruck, AustriaDepartment of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Anichstraße 35, 6020 Innsbruck, AustriaPediatric Nephrology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, GermanyDepartment of Nephrology, UZ Leuven, Leuven, BelgiumDepartment of Pediatric Nephrology, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, Republic of KoreaFocal segmental glomerulosclerosis is a histological pattern on renal biopsy caused by diverse mechanisms. In its primary form, a circulatory factor is implicated in disease onset and recurrence. The natural history of primary FSGS is unpredictable, since some patients are unresponsive towards immunosuppressive measures. Immunologic changes, leading to a proinflammatory or profibrotic milieu, have been implicated in disease progression, namely, glomerular scarring, eventually leading to end-stage renal disease. Among these, interleukin-1ß, tumor-necrosis factor-α (TNF-α), and transforming growth factor-ß1 (TGF-ß1) have emerged as important factors. Translating these findings into clinical practice dampened the enthusiasm, since both TNF-α and TGF-ß1 blockade failed to achieve significant control of the disease. More recently, a role of the complement system has been demonstrated which in fact may be another attractive target in clinical practice. Rituximab, blocking CD20-bearing cells, demonstrated conflicting data regarding efficacy in FSGS. Finally, the T-cell costimulating molecule B7-1 (CD80) is implicated in development of proteinuria in general. Blockade of this target demonstrated significant benefits in a small cohort of resistant patients. Taken together, this review focuses on immunology of FSGS, attributable to either the disease or progression, and discusses novel therapeutic approaches aiming at targeting immunologic factors.http://dx.doi.org/10.1155/2016/2150451 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andreas Kronbichler Johannes Leierer Jun Oh Björn Meijers Jae Il Shin |
spellingShingle |
Andreas Kronbichler Johannes Leierer Jun Oh Björn Meijers Jae Il Shin Immunologic Changes Implicated in the Pathogenesis of Focal Segmental Glomerulosclerosis BioMed Research International |
author_facet |
Andreas Kronbichler Johannes Leierer Jun Oh Björn Meijers Jae Il Shin |
author_sort |
Andreas Kronbichler |
title |
Immunologic Changes Implicated in the Pathogenesis of Focal Segmental Glomerulosclerosis |
title_short |
Immunologic Changes Implicated in the Pathogenesis of Focal Segmental Glomerulosclerosis |
title_full |
Immunologic Changes Implicated in the Pathogenesis of Focal Segmental Glomerulosclerosis |
title_fullStr |
Immunologic Changes Implicated in the Pathogenesis of Focal Segmental Glomerulosclerosis |
title_full_unstemmed |
Immunologic Changes Implicated in the Pathogenesis of Focal Segmental Glomerulosclerosis |
title_sort |
immunologic changes implicated in the pathogenesis of focal segmental glomerulosclerosis |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2016-01-01 |
description |
Focal segmental glomerulosclerosis is a histological pattern on renal biopsy caused by diverse mechanisms. In its primary form, a circulatory factor is implicated in disease onset and recurrence. The natural history of primary FSGS is unpredictable, since some patients are unresponsive towards immunosuppressive measures. Immunologic changes, leading to a proinflammatory or profibrotic milieu, have been implicated in disease progression, namely, glomerular scarring, eventually leading to end-stage renal disease. Among these, interleukin-1ß, tumor-necrosis factor-α (TNF-α), and transforming growth factor-ß1 (TGF-ß1) have emerged as important factors. Translating these findings into clinical practice dampened the enthusiasm, since both TNF-α and TGF-ß1 blockade failed to achieve significant control of the disease. More recently, a role of the complement system has been demonstrated which in fact may be another attractive target in clinical practice. Rituximab, blocking CD20-bearing cells, demonstrated conflicting data regarding efficacy in FSGS. Finally, the T-cell costimulating molecule B7-1 (CD80) is implicated in development of proteinuria in general. Blockade of this target demonstrated significant benefits in a small cohort of resistant patients. Taken together, this review focuses on immunology of FSGS, attributable to either the disease or progression, and discusses novel therapeutic approaches aiming at targeting immunologic factors. |
url |
http://dx.doi.org/10.1155/2016/2150451 |
work_keys_str_mv |
AT andreaskronbichler immunologicchangesimplicatedinthepathogenesisoffocalsegmentalglomerulosclerosis AT johannesleierer immunologicchangesimplicatedinthepathogenesisoffocalsegmentalglomerulosclerosis AT junoh immunologicchangesimplicatedinthepathogenesisoffocalsegmentalglomerulosclerosis AT bjornmeijers immunologicchangesimplicatedinthepathogenesisoffocalsegmentalglomerulosclerosis AT jaeilshin immunologicchangesimplicatedinthepathogenesisoffocalsegmentalglomerulosclerosis |
_version_ |
1725403131754315776 |