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The earlier, the better
BETHESDA, Md.—Groundbreaking diagnostic research on infants has come to light with Precision for Medicine’s Epiontis ID diagnostic monitoring tool, which can screen newborns for more severe inherited diseases than ever before. Earlier screening enables treatment soon after birth, leading to improved disease outcomes and survival as well as advancing treatment for HIV patients. The results of the epigenetic immune monitoring performed by Epiontis ID, an epigenetic quantitative real-time PCR (qPCR), were published in the August issue of the journal Science Translational Medicine.
The norm for many years in screening newborns for inheritable diseases has been to analyze dried blood spots (DBS) from blood taken from a heel-prick. However, with this method, of the 344 known primary immune deficiencies (PIDs), only severe combined immunodeficiencies are detected at birth.
Precision’s novel alternative approach, using epigenetic quantitative real-time PCR (qPCR) assays, was shown in the study to successfully detect a larger number of PIDs such as X-linked agammaglobulinemia, immunodysregulation polyendocrinopathy enteropathy X-linked syndrome and severe congenital neutropenia.
“While further research is needed, these initial results are very encouraging, as they provide early evidence that this epigenetic technology could eventually be a newborn screening method that would identify primary immune diseases that are currently very difficult to detect,” said Dr. Rosa Bacchetta, one of the study investigators and an associate professor in the Department of Pediatrics at the Stanford University School of Medicine. “Typically, children are not diagnosed until they’re sick and showing symptoms, at which point there already is organ impairment and infections that make effective treatment much more difficult. It would be highly advantageous if we could identify these diseases at birth and begin treatment soon after birth, prior to the development of symptoms.”
Sven Olek, a study investigator and managing director of Epiontis GmbH, a German subsidiary of Precision for Medicine that developed Epiontis ID, tells DDNews that under the traditional method of screening newborns, “often by the time symptoms occur, the accurate diagnosis is still far away because children suffer from opportunistic infections or unspecific autoimmunity. This delay may be so dramatic that children succumb to the disease or suffer chronic problems.”
“Since a drop of the patient’s blood can be placed on a piece of paper and mailed into a lab for analysis, this technology eliminates a patient’s need to travel—often long distances—to a facility to have blood drawn,” Olek says. “This method could enable treatment to begin soon after birth, increasing the probability that the patient’s immune cell counts will be more consistently monitored.”
Epiontis ID measures the number of immune cell subtypes from the dried blood spot, which is then compared to a cohort of healthy newborn blood spots, and severe quantitative deficiencies are identified, he explains.
“With the described approach in the study, it is also feasible to detect secondary (or acquired quantitative) immunodeficiencies,” Olek adds. “From the dried blood spot, Epiontis ID allows us to show that certain immune cell populations are deficient (or overly present), as is the case for these diseases.”
The point is, “the doctor now knows what he is treating,” according to Olek. “He is no longer only treating a rare infection or autoimmune reaction, he is treating a genetic disease and knows much better about the limits of antibiotics, for instance, in these patients.”
In the study, researchers report that epigenetic qPCR assays were developed for analysis of human leukocyte subpopulations. Whole blood from 25 healthy donors and 97 HIV positive patients, as well as DBS from 250 healthy newborns and 24 newborns with primary immunodeficiencies, were analyzed and shown to identify newborns suffering from various primary immunodeficiencies.
Precision for Medicine and Epiontis ID are identifying regulatory elements in genes that are expressed in specific cell types, which are “driven” epigenetically, Olek explains. “This means that the genes are switched on when they are not methylated, and switched off when they are methylated. Since this is cell type-specific, we detect demethylation in the specific cell and methylation in all others. Additionally, every cell contains a given number of gene copies (two for all autosomal genes), which are jointly either methylated or not. From this, we can determine the number of specific cells based on the number of the not methylated gene copies.”
Currently, research is being conducted at a German University Hospital, where children of various ages with no immune diseases provide blood via finger prick, Olek tells DDNews.
“Since the immune cell count changes during maturation, and the changes are faster in very young children, we are looking (at the research subjects) on a monthly basis between birth and six months, then on a yearly basis at one-year-old through to 17 years,” he says. “For each age group, we will use Epiontis ID to analyze 20 to 30 healthy donors. This analysis should provide sharper analytical thresholds to detect diseases earlier and more precisely.”