Multiplexing DNA methylation markers to detect circulating cell-free DNA derived from human pancreatic β cells

• DOI: 10.1172/jci.insight.136579
• Publication Date: 2020-06-23T16:29:07Z
• Authors: Daniel Neiman; David Gillis; Sheina Piyanzin; Daniel Cohen; Ori Fridlich; Joshua Moss; Aviad Zick; Tal Oron; Frida Sundberg; Gun Forsander; Oskar Skog; Olle Korsgren; Floris Levy-Khademi; Dan Arbel; Saar Hashavia; A.M. James Shapiro; Cate Speake; Carla Greenbaum; Jennifer Hosford; Amanda Posgai; Mark A. Atkinson; Benjamin Glaser; Desmond A. Schatz; Ruth Shemer; Yuval Dor
• Keywords: Cell-free fetal DNA

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 cell damage type 1 diabetes. Herein we describe an ultrasensitive assay for detection of a cell-specific DNA methylation signature, by simultaneous assessment 6 markers, identifies mixtures containing as little 0.03% (less than genome equivalent). Based on this assay, nondiabetic individuals (N = 218, aged 4-78 years) contained average only equivalent/mL. As expected, cell-free (cfDNA) cells was significantly elevated islet transplant recipients shortly after transplantation. We also detected cfDNA patient with KATP congenital hyperinsulinism, which substantial turnover is thought occur. Strikingly, contrast previous reports, observed no elevation cell-derived autoantibody-positive subjects at risk diabetes 32), recent-onset (<4 months, N 92), or those long-standing disease (>4 38). discuss the utility sensitive analysis potential explanations lack signal