Blood proteome profiling using aptamer-based technology for rejection biomarker discovery in transplantation

AbstractFace transplantation is a promising solution for patients with devastating facial injuries who lack other satisfactory treatment options. At the same time, this type of transplantation is accompanied with high risks of acute transplant rejection. The limitations of traditional skin biopsy and the need to frequently monitor the condition of face transplant call for less invasive biomarkers to better diagnose and treat acute rejection. Discovery of peripheral serum proteins accurately reflecting the transplant status would represent a reasonable solution to meet this demand. However, to date, there is no clinical data available to address the feasibility of this approach. In this study, we used the next generation aptamer-based SOMAscan proteomics platform to profile 1305 proteins of peripheral blood serum in twenty-four samples taken from 6 patients during no-rejection, nonsevere rejection, and severe rejection episodes. Also, we provide a detailed description of biosample processing and all steps to generate and analyze the SOMAscan dataset with hope it will assist in performing biomarker discovery in other transplantation centers using this platform.

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Interference of globin genes with biomarker discovery for allograft rejection in peripheral blood samples

Physiological Genomics ◽

10.1152/physiolgenomics.00216.2007 ◽

2008 ◽

Vol 32 (2) ◽

pp. 190-197 ◽

Cited By ~ 35

Author(s):

Li Li ◽

Lihua Ying ◽

Maarten Naesens ◽

Wenzhong Xiao ◽

Tara Sigdel ◽

...

Keyword(s):

Gene Expression ◽

Whole Blood ◽

Graft Rejection ◽

Peripheral Blood ◽

Biomarker Discovery ◽

Transplant Rejection ◽

Solid Organ ◽

Globin Genes ◽

Blood Samples ◽

Globin Reduction

Microarray technology is a powerful tool in the discovery of new biomarkers for disease. After solid organ transplantation, where the detection of rejection is usually made on invasive biopsies, it could be hypothesized that noninvasive transcriptional profiling of peripheral blood will reveal rejection-specific expression patterns from circulating immune cells. However, in kidney transplant rejection, the analysis of gene expression data in whole blood has proven difficult for detecting significant genes specific for acute graft rejection. Previous studies have demonstrated that the abundance of globin genes in whole blood may mask the underlying biological differences between whole blood samples. In the present study, we compared the gene expression profiles of peripheral blood of nine stable renal allograft recipients with seven matched patients having an ongoing acute renal transplant rejection, using four different protocols of preparation, amplification, and synthesis of cRNA or cDNA and hybridization on the Affymetrix platform. We demonstrated that the globin reduction method is not sufficient to unmask clinically relevant rejection-specific transcriptome profiles in whole blood. Applying an additional mathematical depletion of the globin genes improves the efficacy of globin reduction but cannot remove the confounding influence of globin gene hybridization. Sampling of peripheral blood leukocytes alone, without the confounding influence of globin mRNA, provides sensitive and specific peripheral signatures for graft rejection, with many of these signals overlapping with rejection-driven tissue (kidney)-specific signatures from matched biopsies. Similar applications may exist for array-based biomarker discovery for other diseases associated with changes in leukocyte trafficking, activation, or function.

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Monitoring Of Human Kidney Transplants Using Quantification Of Autologous 111Indium -Oxine Platelet Label Deposition - Beneficial Effect Of PGI2-Treatment In Acute (AR) And Chronic Rejection (CR)

10.1055/s-0038-1652776 ◽

1981 ◽

Author(s):

H Sinzinger ◽

Ch Leithner ◽

M Schwarz

Keyword(s):

Early Diagnosis ◽

Acute Rejection ◽

Serum Creatinine ◽

Beneficial Effect ◽

Transplant Rejection ◽

Human Kidney ◽

Controlled Study ◽

Platelet Deposition ◽

Transplant Function ◽

Diagnosis Of Rejection

Eighty patients with AR and chronic transplant rejection as well as with a stable transplant function were monitored by a combination of quantification of 111In-oxine labeled platelet uptake in the transplanted kidney (under γ- camera) and platelet survival (PS). In acute phase after transplantation the patients were controlled twice or three times a day until 3-4 weeks (weekly platelet labeling) after the transplantation. The quantification of platelet deposition (index (i): transplant region:contralateral region/cts. per 5 minutes) is demonstrated to be a very useful parameter of early diagnosis of rejection crisis. In AR i reaches values up to 2,00, the PS between 24 and 72 hours. In constant transplant function i below 1,20 are found, indicating that also in patients without any clinical sign of rejection, a platelet deposition and a shortening of PS occurs. In 8 patients with CR (i: 1,201,35; PS: 60-96 hours) and one week continuous i.v. PG2-administration (5ng PG2/kg/min) leads to a decrease in platelet deposition (i: minus 0,10-0,15) and a prolongation of PS. In 4 of these patients also the serum creatinine was decreased between 0,5 and 1,1 mg%. Using thereafter a combination of antiplatelet drugs we try now to retain the platelet deposition at the lower level reached by means of the PGI2application. Similar beneficial data could be obtained by treating acute rejection with PGI2-infusion. The preliminary data of a controlled study and the platelet function behaviour during PGI2 are reported.

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TIM3 MRNA QUANTIFICATION IN THE PERIPHERAL BLOOD AND URINARY SEDIMENT CELLS ALLOWS AN ACURATE DIGNOSIS OF ACUTE REJECTION OF KIDNEY ALLOGRAFTS.

Transplantation Journal ◽

10.1097/01.tp.0000331820.64501.6d ◽

2008 ◽

Vol 86 (Supplement) ◽

pp. 308

Author(s):

R Manfro ◽

E Aquino-Dias ◽

G Joelsons ◽

F Veronese ◽

L F. Gonçalves

Keyword(s):

Acute Rejection ◽

Peripheral Blood ◽

Urinary Sediment ◽

Mrna Quantification

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MORPHOLOGICAL CHARACTERISTICS OF PERIPHERAL BLOOD OF COWS INFECTED WITH BLV AND THE FREQUENCY OF REGISTRATION OF LEUKEMOID REACTIONS IN COWS WITH LEUKEMIA-AFFECTED HERDS

Innovations and Food Safety ◽

10.31677/2311-0651-2020-27-1-66-72 ◽

2020 ◽

pp. 66-72

Author(s):

P. N. Smirnov ◽

S. M. Chudum ◽

I. V. Trostyansky ◽

O. S. Kotlyarova

Keyword(s):

Successful Treatment ◽

Peripheral Blood ◽

Serum Proteins ◽

Morphological Characteristics ◽

Controlled Experiments ◽

Individual Analysis ◽

Morphological Composition ◽

Inflammatory Processes

In controlled experiments during planned studies of cattle for leukemia, animals that showed leukemoid changes in blood – quantitative redistribution of granulocytes and agranulocytes-were identified. Individual analysis revealed that granulocytosis was detected in animals with inflammatory processes. In addition, the article presents comparative indicators of serum proteins in cows at the hematological stage of the leukemic process, with the manifestation of leukemoid reactions and in clinically healthy cows. Characteristic changes in the synthesis of immunoglobulins in cows with leukemia and leukemoid changes in the morphological composition of blood were established. With successful treatment of inflammatory processes, the hematological status of cows is restored to the initial indicators.

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