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Multiplexing DNA methylation markers to detect circulating cell-free DNA derived from human pancreatic β cells
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- Neiman, Daniel (författare)
- Hebrew Univ Jerusalem, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, Hadassah Med Sch, Jerusalem, Israel.
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- Gillis, David (författare)
- Hadassah Hebrew Univ, Endocrine Unit, Dept Pediat, Med Ctr, Jerusalem, Israel.
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- Piyanzin, Sheina (författare)
- Hebrew Univ Jerusalem, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, Hadassah Med Sch, Jerusalem, Israel.
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- Hebrew Univ Jerusalem, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, Hadassah Med Sch, Jerusalem, Israel Hadassah Hebrew Univ, Endocrine Unit, Dept Pediat, Med Ctr, Jerusalem, Israel. (creator_code:org_t)
- 2020-07-23
- 2020
- Engelska.
- Ingår i: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 5:14
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- It has been proposed that unmethylated insulin promoter fragments in plasma derive exclusively from β cells, reflect their recent demise, and can be used to assess β cell damage in type 1 diabetes. Herein we describe an ultrasensitive assay for detection of a β cell–specific DNA methylation signature, by simultaneous assessment of 6 DNA methylation markers, that identifies β cell DNA in mixtures containing as little as 0.03% β cell DNA (less than 1 β cell genome equivalent). Based on this assay, plasma from nondiabetic individuals (N = 218, aged 4–78 years) contained on average only 1 β cell genome equivalent/mL. As expected, cell-free DNA (cfDNA) from β cells was significantly elevated in islet transplant recipients shortly after transplantation. We also detected β cell cfDNA in a patient with KATP congenital hyperinsulinism, in which substantial β cell turnover is thought to occur. Strikingly, in contrast to previous reports, we observed no elevation of β cell–derived cfDNA in autoantibody-positive subjects at risk for type 1 diabetes (N = 32), individuals with recent-onset type 1 diabetes (<4 months, N = 92), or those with long-standing disease (>4 months, N = 38). We discuss the utility of sensitive β cell cfDNA analysis and potential explanations for the lack of a β cell cfDNA signal in type 1 diabetes.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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- Neiman, Daniel
- Gillis, David
- Piyanzin, Sheina
- Cohen, Daniel
- Fridlich, Ori
- Moss, Joshua
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- Zick, Aviad
- Oron, Tal
- Sundberg, Frida
- Forsander, Gun
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- Hashavia, Saar
- Shapiro, A. M. J ...
- Speake, Cate
- Greenbaum, Carla
- Hosford, Jennife ...
- Posgai, Amanda
- Atkinson, Mark A ...
- Glaser, Benjamin
- Schatz, Desmond ...
- Shemer, Ruth
- Dor, Yuval
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