Immunologic Changes Implicated in the Pathogenesis of Focal Segmental Glomerulosclerosis
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Immunologic Changes Implicated in the Pathogenesis of Focal Segmental Glomerulosclerosis. / Kronbichler, Andreas; Leierer, Johannes; Oh, Jun; Meijers, Björn; Shin, Jae Il.
In: BIOMED RES INT , Vol. 2016, 2016, p. 2150451.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Immunologic Changes Implicated in the Pathogenesis of Focal Segmental Glomerulosclerosis
AU - Kronbichler, Andreas
AU - Leierer, Johannes
AU - Oh, Jun
AU - Meijers, Björn
AU - Shin, Jae Il
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
U2 - 10.1155/2016/2150451
DO - 10.1155/2016/2150451
M3 - SCORING: Journal article
C2 - 26989679
VL - 2016
SP - 2150451
JO - BIOMED RES INT
JF - BIOMED RES INT
SN - 2314-6133
ER -