1506-P: Genomic Monitoring of Islet Graft Injury in Type 1 Diabetic Patients after Islet Transplantation

Introduction & Objective: Early detection of islet graft injury after islet transplantation (IT) may allow timely intervention to preserve islet graft health and function. We hypothesized that in response to IT injury, islet beta-cells will release cell-free DNA (cfDNA) into the circulation allo...

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Veröffentlicht in:Diabetes (New York, N.Y.) N.Y.), 2024-06, Vol.73, p.1
Hauptverfasser: Husseiny, Mohamed I, Cobb, Jacob, Orr, Chris, Hacker-Stratton, Jeannette, ouhar, Elena, El-Shahawy, Mohamed A, Kandeel, Fouad R
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container_start_page 1
container_title Diabetes (New York, N.Y.)
container_volume 73
creator Husseiny, Mohamed I
Cobb, Jacob
Orr, Chris
Hacker-Stratton, Jeannette
ouhar, Elena
El-Shahawy, Mohamed A
Kandeel, Fouad R
description Introduction & Objective: Early detection of islet graft injury after islet transplantation (IT) may allow timely intervention to preserve islet graft health and function. We hypothesized that in response to IT injury, islet beta-cells will release cell-free DNA (cfDNA) into the circulation allowing for early detection of graft injury. Methods: Real-time bidirectional pyrophosphorolysis-activated PCR (Bi-PAP) and methylation-specific PCR (MSP) assays were developed to detect donor cfDNA and beta-cell specific unmethylated insulin DNA in plasma of individuals with type 1 diabetes who received IT. Under approved protocols at the City of Hope National Medical Center, blood samples from type 1 diabetic IT individuals (n=22) were collected before and after the procedure and analyzed using the Bi-PAP and MSP assays. The longitudinal relationships between the metabolic and immunologic parameters and the appearance of donor-specific cfDNA in circulation of individuals after IT were analyzed. Results: All individuals that underwent IT showed donor-specific cfDNA in plasma (by both methods) on day one after the procedure. Donor-specific cfDNA decreased gradually and was no longer detected in the plasma by day 18 post-IT. Insulin independence and less variation in blood glucose levels after IT was associated with minimal to no plasma donor cfDNA during the study period. In contrast, individuals that did not achieve insulin independence, had wide swings in blood glucose, or that had immune activation after IT were found to have increases in donor cfDNA. Conclusion: Donor islet cfDNA persisted in individuals with poorer outcomes after IT. These findings suggest that donor cfDNA may be markers of islet injury after allo-transplantation. It remains to be seen if donor cfDNA levels provide more insights sooner than other techniques currently employed to monitor islet health after transplantation.
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We hypothesized that in response to IT injury, islet beta-cells will release cell-free DNA (cfDNA) into the circulation allowing for early detection of graft injury. Methods: Real-time bidirectional pyrophosphorolysis-activated PCR (Bi-PAP) and methylation-specific PCR (MSP) assays were developed to detect donor cfDNA and beta-cell specific unmethylated insulin DNA in plasma of individuals with type 1 diabetes who received IT. Under approved protocols at the City of Hope National Medical Center, blood samples from type 1 diabetic IT individuals (n=22) were collected before and after the procedure and analyzed using the Bi-PAP and MSP assays. The longitudinal relationships between the metabolic and immunologic parameters and the appearance of donor-specific cfDNA in circulation of individuals after IT were analyzed. Results: All individuals that underwent IT showed donor-specific cfDNA in plasma (by both methods) on day one after the procedure. Donor-specific cfDNA decreased gradually and was no longer detected in the plasma by day 18 post-IT. Insulin independence and less variation in blood glucose levels after IT was associated with minimal to no plasma donor cfDNA during the study period. In contrast, individuals that did not achieve insulin independence, had wide swings in blood glucose, or that had immune activation after IT were found to have increases in donor cfDNA. Conclusion: Donor islet cfDNA persisted in individuals with poorer outcomes after IT. These findings suggest that donor cfDNA may be markers of islet injury after allo-transplantation. It remains to be seen if donor cfDNA levels provide more insights sooner than other techniques currently employed to monitor islet health after transplantation.</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/db24-1506-P</identifier><language>eng</language><publisher>New York: American Diabetes Association</publisher><subject>Allografts ; Beta cells ; Blood glucose ; Blood levels ; Diabetes ; Diabetes mellitus (insulin dependent) ; DNA methylation ; Immune response ; Insulin ; Islet cells ; Pancreas ; Pancreatic islet transplantation ; Plasma ; Polymerase chain reaction ; Pyrophosphorolysis</subject><ispartof>Diabetes (New York, N.Y.), 2024-06, Vol.73, p.1</ispartof><rights>Copyright American Diabetes Association Jun 2024</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Husseiny, Mohamed I</creatorcontrib><creatorcontrib>Cobb, Jacob</creatorcontrib><creatorcontrib>Orr, Chris</creatorcontrib><creatorcontrib>Hacker-Stratton, Jeannette</creatorcontrib><creatorcontrib>ouhar, Elena</creatorcontrib><creatorcontrib>El-Shahawy, Mohamed A</creatorcontrib><creatorcontrib>Kandeel, Fouad R</creatorcontrib><title>1506-P: Genomic Monitoring of Islet Graft Injury in Type 1 Diabetic Patients after Islet Transplantation</title><title>Diabetes (New York, N.Y.)</title><description>Introduction &amp; Objective: Early detection of islet graft injury after islet transplantation (IT) may allow timely intervention to preserve islet graft health and function. We hypothesized that in response to IT injury, islet beta-cells will release cell-free DNA (cfDNA) into the circulation allowing for early detection of graft injury. Methods: Real-time bidirectional pyrophosphorolysis-activated PCR (Bi-PAP) and methylation-specific PCR (MSP) assays were developed to detect donor cfDNA and beta-cell specific unmethylated insulin DNA in plasma of individuals with type 1 diabetes who received IT. Under approved protocols at the City of Hope National Medical Center, blood samples from type 1 diabetic IT individuals (n=22) were collected before and after the procedure and analyzed using the Bi-PAP and MSP assays. The longitudinal relationships between the metabolic and immunologic parameters and the appearance of donor-specific cfDNA in circulation of individuals after IT were analyzed. Results: All individuals that underwent IT showed donor-specific cfDNA in plasma (by both methods) on day one after the procedure. Donor-specific cfDNA decreased gradually and was no longer detected in the plasma by day 18 post-IT. Insulin independence and less variation in blood glucose levels after IT was associated with minimal to no plasma donor cfDNA during the study period. In contrast, individuals that did not achieve insulin independence, had wide swings in blood glucose, or that had immune activation after IT were found to have increases in donor cfDNA. Conclusion: Donor islet cfDNA persisted in individuals with poorer outcomes after IT. These findings suggest that donor cfDNA may be markers of islet injury after allo-transplantation. It remains to be seen if donor cfDNA levels provide more insights sooner than other techniques currently employed to monitor islet health after transplantation.</description><subject>Allografts</subject><subject>Beta cells</subject><subject>Blood glucose</subject><subject>Blood levels</subject><subject>Diabetes</subject><subject>Diabetes mellitus (insulin dependent)</subject><subject>DNA methylation</subject><subject>Immune response</subject><subject>Insulin</subject><subject>Islet cells</subject><subject>Pancreas</subject><subject>Pancreatic islet transplantation</subject><subject>Plasma</subject><subject>Polymerase chain reaction</subject><subject>Pyrophosphorolysis</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNqNi7FuwjAURS1EJULbqT_wpM4ufnaLCWuhlAGJIUM3ZMBpHYXnYDsDf48l-IDqDnc45zD2guJNKqUnx7185_ghpnw7YAWWquRK6p8hK4RAyVGXesTGMTZCiGlewf5u9hxWlvzJHWDjySUfHP2Cr2EdW5tgFUydYE1NHy7gCKpLZwFh4czeptxsTXKWUoSs2XCPqmAodq2hlKmnJ_ZQmzba5_s_stevZfX5zbvgz72Nadf4PlBGO4WIUqsSZ-p_1hVVj0uq</recordid><startdate>20240601</startdate><enddate>20240601</enddate><creator>Husseiny, Mohamed I</creator><creator>Cobb, Jacob</creator><creator>Orr, Chris</creator><creator>Hacker-Stratton, Jeannette</creator><creator>ouhar, Elena</creator><creator>El-Shahawy, Mohamed A</creator><creator>Kandeel, Fouad R</creator><general>American Diabetes Association</general><scope>K9.</scope><scope>NAPCQ</scope></search><sort><creationdate>20240601</creationdate><title>1506-P: Genomic Monitoring of Islet Graft Injury in Type 1 Diabetic Patients after Islet Transplantation</title><author>Husseiny, Mohamed I ; Cobb, Jacob ; Orr, Chris ; Hacker-Stratton, Jeannette ; ouhar, Elena ; El-Shahawy, Mohamed A ; Kandeel, Fouad R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-proquest_journals_31112739183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Allografts</topic><topic>Beta cells</topic><topic>Blood glucose</topic><topic>Blood levels</topic><topic>Diabetes</topic><topic>Diabetes mellitus (insulin dependent)</topic><topic>DNA methylation</topic><topic>Immune response</topic><topic>Insulin</topic><topic>Islet cells</topic><topic>Pancreas</topic><topic>Pancreatic islet transplantation</topic><topic>Plasma</topic><topic>Polymerase chain reaction</topic><topic>Pyrophosphorolysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Husseiny, Mohamed I</creatorcontrib><creatorcontrib>Cobb, Jacob</creatorcontrib><creatorcontrib>Orr, Chris</creatorcontrib><creatorcontrib>Hacker-Stratton, Jeannette</creatorcontrib><creatorcontrib>ouhar, Elena</creatorcontrib><creatorcontrib>El-Shahawy, Mohamed A</creatorcontrib><creatorcontrib>Kandeel, Fouad R</creatorcontrib><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Husseiny, Mohamed I</au><au>Cobb, Jacob</au><au>Orr, Chris</au><au>Hacker-Stratton, Jeannette</au><au>ouhar, Elena</au><au>El-Shahawy, Mohamed A</au><au>Kandeel, Fouad R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>1506-P: Genomic Monitoring of Islet Graft Injury in Type 1 Diabetic Patients after Islet Transplantation</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><date>2024-06-01</date><risdate>2024</risdate><volume>73</volume><spage>1</spage><pages>1-</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><abstract>Introduction &amp; Objective: Early detection of islet graft injury after islet transplantation (IT) may allow timely intervention to preserve islet graft health and function. We hypothesized that in response to IT injury, islet beta-cells will release cell-free DNA (cfDNA) into the circulation allowing for early detection of graft injury. Methods: Real-time bidirectional pyrophosphorolysis-activated PCR (Bi-PAP) and methylation-specific PCR (MSP) assays were developed to detect donor cfDNA and beta-cell specific unmethylated insulin DNA in plasma of individuals with type 1 diabetes who received IT. Under approved protocols at the City of Hope National Medical Center, blood samples from type 1 diabetic IT individuals (n=22) were collected before and after the procedure and analyzed using the Bi-PAP and MSP assays. The longitudinal relationships between the metabolic and immunologic parameters and the appearance of donor-specific cfDNA in circulation of individuals after IT were analyzed. Results: All individuals that underwent IT showed donor-specific cfDNA in plasma (by both methods) on day one after the procedure. Donor-specific cfDNA decreased gradually and was no longer detected in the plasma by day 18 post-IT. Insulin independence and less variation in blood glucose levels after IT was associated with minimal to no plasma donor cfDNA during the study period. In contrast, individuals that did not achieve insulin independence, had wide swings in blood glucose, or that had immune activation after IT were found to have increases in donor cfDNA. Conclusion: Donor islet cfDNA persisted in individuals with poorer outcomes after IT. These findings suggest that donor cfDNA may be markers of islet injury after allo-transplantation. It remains to be seen if donor cfDNA levels provide more insights sooner than other techniques currently employed to monitor islet health after transplantation.</abstract><cop>New York</cop><pub>American Diabetes Association</pub><doi>10.2337/db24-1506-P</doi></addata></record>
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subjects Allografts
Beta cells
Blood glucose
Blood levels
Diabetes
Diabetes mellitus (insulin dependent)
DNA methylation
Immune response
Insulin
Islet cells
Pancreas
Pancreatic islet transplantation
Plasma
Polymerase chain reaction
Pyrophosphorolysis
title 1506-P: Genomic Monitoring of Islet Graft Injury in Type 1 Diabetic Patients after Islet Transplantation
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