Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\24700868
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Am+Soc+Nephrol
2014 ; 25
(10
): 2291-302
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Spleen tyrosine kinase inhibition attenuates autoantibody production and reverses
experimental autoimmune GN
#MMPMID24700868
McAdoo SP
; Reynolds J
; Bhangal G
; Smith J
; McDaid JP
; Tanna A
; Jackson WD
; Masuda ES
; Cook HT
; Pusey CD
; Tam FW
J Am Soc Nephrol
2014[Oct]; 25
(10
): 2291-302
PMID24700868
show ga
Spleen tyrosine kinase (SYK) has an important role in immunoreceptor signaling,
and SYK inhibition has accordingly attenuated immune-mediated injury in several
in vivo models. However, the effect of SYK inhibition on autoantibody production
remains unclear, and SYK inhibition has not been studied in an autoimmune model
of renal disease. We, therefore, studied the effect of SYK inhibition in
experimental autoimmune GN, a rodent model of antiglomerular basement membrane
disease. We show glomerular SYK expression and activation by immunohistochemistry
in both experimental and clinical disease, and we show that treatment with
fostamatinib, a small molecule kinase inhibitor selective for SYK, completely
prevents the induction of experimental autoimmune GN. In established experimental
disease, introduction of fostamatinib treatment led to cessation of autoantibody
production, reversal of renal injury, preservation of biochemical renal function,
and complete protection from lung hemorrhage. B cell ELISpot and flow cytometric
analysis suggest that short-term fostamatinib treatment inhibits the generation
and activity of antigen-specific B cells without affecting overall B-cell
survival. Additionally, fostamatinib inhibited proinflammatory cytokine
production by nephritic glomeruli ex vivo and cultured bone marrow-derived
macrophages in vitro, suggesting additional therapeutic effects independent of
effects on autoantibody production that are likely related to inhibited Fc
receptor signaling within macrophages in diseased glomeruli. Given these
encouraging results in an in vivo model that is highly applicable to human
disease, we believe clinical studies targeting SYK in GN are now warranted.
|Aminopyridines
[MESH]
|Animals
[MESH]
|Anti-Glomerular Basement Membrane Disease/*immunology/*prevention & control
[MESH]
|Antibody Formation/*drug effects
[MESH]
|Autoantibodies/blood
[MESH]
|Disease Models, Animal
[MESH]
|Drug Evaluation, Preclinical
[MESH]
|Female
[MESH]
|Humans
[MESH]
|Intracellular Signaling Peptides and Proteins/antagonists &
inhibitors/*metabolism
[MESH]
free
free
free
