scholarly journals Polyreactive Antibodies Developing Amidst Humoral Rejection of Human Kidney Grafts Bind Apoptotic Cells and Activate Complement

2013 ◽  
Vol 13 (10) ◽  
pp. 2590-2600 ◽  
Author(s):  
F. Porcheray ◽  
J. W. Fraser ◽  
B. Gao ◽  
A. McColl ◽  
J. DeVito ◽  
...  
Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3499
Author(s):  
Stefan Reuter ◽  
Dominik Kentrup ◽  
Alexander Grabner ◽  
Gabriele Köhler ◽  
Konrad Buscher ◽  
...  

In the context of transplantation, complement activation is associated with poor prognosis and outcome. While complement activation in antibody-mediated rejection is well-known, less is known about complement activation in acute T cell-mediated rejection (TCMR). There is increasing evidence that complement contributes to the clearance of apoptotic debris and tissue repair. In this regard, we have analysed published human kidney biopsy transcriptome data clearly showing upregulated expression of complement factors in TCMR. To clarify whether and how the complement system is activated early during acute TCMR, experimental syngeneic and allogeneic renal transplantations were performed. Using an allogeneic rat renal transplant model, we also observed upregulation of complement factors in TCMR in contrast to healthy kidneys and isograft controls. While staining for C4d was positive, staining with a C3d antibody showed no C3d deposition. FACS analysis of blood showed the absence of alloantibodies that could have explained the C4d deposition. Gene expression pathway analysis showed upregulation of pro-apoptotic factors in TCMR, and apoptotic endothelial cells were detected by ultrastructural analysis. Monocytes/macrophages were found to bind to and phagocytise these apoptotic cells. Therefore, we conclude that early C4d deposition in TCMR may be relevant to the clearance of apoptotic cells.


2010 ◽  
Vol 10 (11) ◽  
pp. 2463-2471 ◽  
Author(s):  
W. Wong ◽  
J. DeVito ◽  
H. Nguyen ◽  
D. Sarracino ◽  
F. Porcheray ◽  
...  

2010 ◽  
Vol 89 (10) ◽  
pp. 1239-1246 ◽  
Author(s):  
Fabrice Porcheray ◽  
Julie DeVito ◽  
Beow Y. Yeap ◽  
Lijuan Xue ◽  
Ian Dargon ◽  
...  

2005 ◽  
Vol 173 (4S) ◽  
pp. 300-300
Author(s):  
Sreedhar Sagi ◽  
Lutz Trojan ◽  
Peter Aiken ◽  
Maurice S. Michel ◽  
Thomas Knoll

2005 ◽  
Vol 173 (4S) ◽  
pp. 103-103
Author(s):  
Adam G. Baseman ◽  
Andrew J. Kirsch ◽  
Fray F. Marshall ◽  
Haiyen E. Zhau ◽  
Leland W.K. Chung ◽  
...  

1975 ◽  
Vol 80 (1_Suppla) ◽  
pp. S51 ◽  
Author(s):  
H. Bojar ◽  
J. L. Wittliff ◽  
K. Balzer ◽  
R. Dreyfürst ◽  
F. Boeminghaus ◽  
...  

2020 ◽  
Author(s):  
Elizabeth Neumann ◽  
Lukasz Migas ◽  
Jamie L. Allen ◽  
Richard Caprioli ◽  
Raf Van de Plas ◽  
...  

<div> <div> <p>Small metabolites are essential for normal and diseased biological function but are difficult to study because of their inherent structural complexity. MALDI imaging mass spectrometry (IMS) of small metabolites is particularly challenging as MALDI matrix clusters are often isobaric with metabolite ions, requiring high resolving power instrumentation or derivatization to circumvent this issue. An alternative to this is to perform ion mobility separation before ion detection, enabling the visualization of metabolites without the interference of matrix ions. Here, we use MALDI timsTOF IMS to image small metabolites at high spatial resolution within the human kidney. Through this, we have found metabolites, such as arginic acid, acetylcarnitine, and choline that localize to the cortex, medulla, and renal pelvis, respectively. We have also demonstrated that trapped ion mobility spectrometry (TIMS) can resolve matrix peaks from metabolite signal and separate both isobaric and isomeric metabolites with different localizations within the kidney. The added ion mobility data dimension dramatically increased the peak capacity for molecular imaging experiments. Future work will involve further exploring the small metabolite profiles of human kidneys as a function of age, gender, and ethnicity.</p></div></div>


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