Genomics: Insight

Cell-free DNA (cfDNA) as potential biomarker for disease and prenatal genetic screening.

cfDNA as a potential biomarker as part of diagnosis and monitoring of autoimmune diseases (AIDs).

Temidayo Adegbenro
July 11, 2023

Research on cfDNA reveals that it can be used as a biomarker, or indicator, for diseases with pathologies it directly contributes to, and its potential to be used to identify and monitor autoimmune diseases in patients. cfDNA are fragments of double-stranded DNA, typically between 100 and 200 base pairs1. These short fragments of DNA are released from the nucleus into the blood circulation and other body fluids1. Impairment in the processes that remove cfDNA leads to its accumulation2. Excess cfDNA levels in the body produces an immunogenic response and has proven to activate the immune system2. Multiple autoimmune diseases including systemic lupus erythematosus (SLE), a disease that affects several organs and tissues in the body and is worsened by autoinflammatory responses from elevated cfDNA levels2. As more research illuminates our understanding on the biological processes responsible for cfDNA regulation, it can serve as a tool to monitor disease activity in patients during and after treatment2.

Dysregulation of cfDNA-producing pathway leads to cfDNA increase, attributing to autoimmune diseases.

Apoptosis, or programed cell-death, is a normal function in healthy cells and tissues, serving to degrade cellular waste products and necrotized tissues due to trauma2. cfDNA that is not effectively cleared accumulates, becomes antigenic and thus leads to the body to perceive this “self-cfDNA” as a foreign pathogen2. The immune system is activated and sends signals for immune cells to create episodes of inflammation that attacks organs, tissues, and joints2. The immunostimulatory nature of cfDNA makes it a major contributor of autoimmune diseases while simultaneously serving as a biological indicator for disease activity in patients2.

Major obstacle preventing use of cfDNA as a diagnostic tool in patients suffering from autoimmune diseases.

One limitation of cfDNA as a biomarker is that patients suffering from autoimmune diseases is the variable levels of severity which can correlate to a variable amount of cfDNA in patient samples2. This variation makes it difficult to produce a uniform range of pathologic cfDNA levels2. One solution to this problem is to make the sampling source type the same for sample collection in all individuals suspected of suffering from autoimmune diseases2. A uniform sampling type (plasma, serum, or synovial fluid) could also help make quantification of cfDNA levels in patients more accurate2.

Second clinical application of cfDNA: noninvasive prenatal testing

Sampling of cell-free placental DNA in a mother’s blood circulation can provide information on abnormal fetal chromosomes without risk to the unborn child3. The standard testing method uses chorionic villus sampling which is associated with a low, but real risk of miscarriage from the procedure. This reality discourages many pregnant women from getting tested3. cfDNA screening is also more sensitive than the current testing and can test a variety of chromosomal abnormalities3. Since cfDNA screening can be conducted by drawing maternal blood, testing can be made more accessible for resource-poor areas that do not have adequate medical facilities that offer sonographies or maternal care from physicians3.

Various factors may impact pregnant women’s decision-making in light of prenatal screening results.

There have been concerns about the implications of the information acquired by prenatal screening. Sociocultural, economic, religious, and political environments, as well as healthcare systems often influences people’s perceptions and attitudes about maternity and childrearing3. Consequently, these factors can also influence the choices that pregnant women make regarding their pregnancies3. For example, cultural attitudes about the quality of life for children with birth defects may impact a pregnant woman’s beliefs and decisions regarding her pregnancy3. Along with this innovative method for genetic testing, should be the accompaniment of maternal care resources including emotional and mental support services (i.e. family, friends) that can help prepare them for motherhood.


The biological processes responsible for increased cfDNA levels in the body, as well as important pathways that activate the immune system continue to be investigated. Consequently, cfDNA stimulates the immune system and leads to disease progression. In this context, it can be used to diagnose and monitor disease activity in patients suspected of having such autoimmune diseases. It also has potential to be used for testing genetic abnormalities in a way that doesn’t place pregnant women or their unborn child(ren) at risk3. With more technological advancement and modifications in global healthcare, expecting mothers can know the health status of their child(ren) to prepare them for motherhood worldwide3.


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About the Author

Temidayo Adegbenro

Current postbaccalaureate NCATS trainee with NIH Intramural Research program.