BACKGROUND: Increased concentrations of cell-free DNA have been found in several disorders and have been interpreted as evidence of increased rates of cell death or turnover. Evidence from in vitro and animal experiments suggests that DNA may play a role in the pathogenesis of rheumatoid arthritis (RA). METHODS: We measured cell-free DNA in plasma and serum from patients with RA and healthy controls by use of quantitative PCR for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) DNA. We used protein G Sepharosetrade mark bead adsorption of plasma and elution to isolate antibody-bound DNA. RESULTS: In paired plasma and serum samples of 16 healthy controls the median GAPDH copies were 4500 genome equivalents (GE)/mL plasma (range 319-21 000) and in 26 RA patients 17 000 GE/mL plasma (2100-2 375 000, P = 0.0001). In the serum from normal controls the median GAPDH copies were 35 000 GE/mL (1700-239 000) and from RA patients 222 000 GE/mL (21 000-2 375 000, P = 0.004). A median of 81% of the cell-free DNA in RA was associated with antibody compared with 9% in healthy controls (P = 0.001). The concentrations of DNA did not vary with the type of therapy patients received. CONCLUSIONS: These results provide new evidence for a role of cell-free DNA-antibody complexes in the etiology of RA, suggest new avenues for basic research, and may prove to be relevant to diagnosis and assessment of therapy.
BACKGROUND: Increased concentrations of cell-free DNA have been found in several disorders and have been interpreted as evidence of increased rates of cell death or turnover. Evidence from in vitro and animal experiments suggests that DNA may play a role in the pathogenesis of rheumatoid arthritis (RA). METHODS: We measured cell-free DNA in plasma and serum from patients with RA and healthy controls by use of quantitative PCR for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) DNA. We used protein G Sepharosetrade mark bead adsorption of plasma and elution to isolate antibody-bound DNA. RESULTS: In paired plasma and serum samples of 16 healthy controls the median GAPDH copies were 4500 genome equivalents (GE)/mL plasma (range 319-21 000) and in 26 RApatients 17 000 GE/mL plasma (2100-2 375 000, P = 0.0001). In the serum from normal controls the median GAPDH copies were 35 000 GE/mL (1700-239 000) and from RApatients 222 000 GE/mL (21 000-2 375 000, P = 0.004). A median of 81% of the cell-free DNA in RA was associated with antibody compared with 9% in healthy controls (P = 0.001). The concentrations of DNA did not vary with the type of therapy patients received. CONCLUSIONS: These results provide new evidence for a role of cell-free DNA-antibody complexes in the etiology of RA, suggest new avenues for basic research, and may prove to be relevant to diagnosis and assessment of therapy.
Authors: Re-I Chin; Kevin Chen; Abul Usmani; Chanelle Chua; Peter K Harris; Michael S Binkley; Tej D Azad; Jonathan C Dudley; Aadel A Chaudhuri Journal: Mol Diagn Ther Date: 2019-06 Impact factor: 4.074
Authors: Carrie L Butler; Michelle J Hickey; Ning Jiang; Ying Zheng; David Gjertson; Qiuheng Zhang; Ping Rao; Gregory A Fishbein; Martin Cadeiras; Mario C Deng; Hector L Banchs; Guillermo Torre; David DeNofrio; Howard J Eisen; Jon Kobashigawa; Randall C Starling; Abdallah Kfoury; Adrian Van Bakel; Gregory Ewald; Ivan Balazs; Arnold S Baas; Daniel Cruz; Reza Ardehali; Reshma Biniwale; Murray Kwon; Abbas Ardehali; Ali Nsair; Bryan Ray; Elaine F Reed Journal: Am J Transplant Date: 2020-04-26 Impact factor: 8.086
Authors: Hada C Macher; Maria A Martinez-Broca; Amalia Rubio-Calvo; Cristina Leon-Garcia; Manuel Conde-Sanchez; Alzenira Costa; Elena Navarro; Juan M Guerrero Journal: PLoS One Date: 2012-12-07 Impact factor: 3.240