Credit: Максим Кукушкин
Immunosignaturing can allow for early detection of multiple myeloma and a range of other cancers, according to research published in PNAS.
Immunosignaturing involves profiling the entire population of antibodies circulating in the blood at a given time.
The method allowed researchers to distinguish 14 separate diseases, including 12 cancers, from one another and from healthy controls. The specificity was greater than 98% for each diagnosis.
“For years, we’ve seen remarkable results from immunosignatures, but introducing the technology to the scientific community has required a lot of patience,” said study author Phillip Stafford, PhD, of Arizona State University in Tempe.
The technique relies on a microarray consisting of thousands of random sequence peptides, imprinted on a glass slide. When a tiny droplet of blood (less than a microliter is needed) is spread across the microarray, antibodies in the blood selectively bind with individual peptides, forming a portrait of immune activity—an immunosignature.
Because the peptide sequences are random and not related to any naturally occurring disease antigens, the immunosignatures are “disease agnostic,” which means a single platform is potentially applicable to multiple disease types.
With their research, Dr Stafford and his colleagues put this claim to the test. The team first “trained” the system to calibrate results and establish reference immunosignatures using 20 samples each from 5 cancer patient cohorts, along with 20 non-cancer patients.
Once reference immunosignatures were established, the researchers tested the technique in a blind evaluation of 120 independent samples covering the same diseases. The results demonstrated 95% accuracy.
To further assess the diagnostic power of immunosignaturing, the team tested more than 1500 historical samples comprising 14 different diseases. This included 12 cancers, such as breast, brain, and multiple myeloma.
The average diagnostic accuracy of immunosignaturing was greater than 98% for each diagnosis, which suggests the method is suitable for the simultaneous classification of multiple diseases.
In a pairwise test against healthy control samples, multiple myeloma samples displayed the most significantly different peptides by t test. Of the top 100 peptides selected in this way, only breast cancer showed no overlap with any other disease.
Nevertheless, the researchers were able to distinguish the 14 separate diseases from one another, as well as from healthy controls, through immunosignatures.
Dr Stafford and his colleagues said these results suggest that immunosignatures provide an attractive means of capturing disease complexity. They offer a marked improvement over traditional methods in which one-to-one molecular recognition events are measured and a small number of analytes can be evaluated.
Furthermore, the technology is flexible in terms of handling and processing, the team said. A dried sample of blood, collected on filter paper and mailed to a study facility, can be used to generate an immunosignature.
The researchers also pointed out that the microarray chip used for this study contains 10,000 imprinted peptides, and this allows for enhanced sensitivity, owing to the large number of different possible signals elicited.
However, a significant improvement in immunosignaturing sensitivity and accuracy might be achieved through new chip technology. The team is currently developing a chip imprinted with more than 100,000 peptides.
