New Ultra-Sensitive Test Could Allow for Earlier Detection of HIV & Cancers

In a recent study, scientists have developed a new ultra-sensitive screening technique for diseases such as HIV and cancers that may be 10,000 times more sensitive than those currently used clinical tests.

Cheng-ting Tsai, University of California, Berkeley, and colleagues published the results of their study in ACS Central Science.

“Of all the protein types one might want to detect in a clinical setting, antibodies are by far the most numerous,” the authors write. “They are used as biomarkers of autoimmune diseases, cancers, infectious diseases, neurological disorders, and vaccine efficacy.”

Indeed, many clinical blood tests are based on immunoassays, which use highly specific antibodies or other ligands to detect the presence of specific molecules, including antibodies that are associated with the presence of a particular disease.

Despite the value of using antibodies as clinical diagnostic markers, however, many conventional immunoassays are subject to problems, such as epitope masking and protein denaturation.

As a consequence, Tsai and colleagues conducted a study to design a test to help overcome these problems. They developed a screening test, termed antibody detection by agglutination-polymerase chain reaction (PCR; ADAP), that detects disease-associated antibodies or related biomarkers in the blood.

The team improved the traditional immunoassay procedure by harnessing the key features of a classic latex agglutination assay (based on antigen—antibody complex formation) with those of a proximity ligation assay (in which protein–protein complexes are detected by PCR amplification). This powerful combination creates an ultra-sensitive screening test that detects zepto- to attomoles of antibodies in 2 μL of sample.

In particular, they used ADAP to detect anti-thyroglobulin autoantibodies in patient samples. These autoantibodies are diagnostic of autoimmune thyroiditis and can also serve as a biomarker for monitoring thyroid cancer recurrence following thyroidectomy. Although radioimmunoassays are currently used to detect these autoantibodies, only specialized laboratories can perform this test, due to the strict regulations for use and disposal of radioactive reagents used in the test.

Using ADAP, the team detected anti-thyroglobulin autoantibodies with a 1,000-fold increased sensitivity over a United States Food and Drug Administration (FDA)-approved radioimmunoassay.

“ADAP is 3 orders of magnitude more sensitive than clinically used assays, creating new possibilities for the early detection and treatment of disease,” the authors write.

They also noted that ADAP could be easily adapted to many new point-of-care PCR platforms to provide highly sensitive screening tests in low resource settings. More precise screening could allow for much earlier detection and treatment of specific diseases, and also help to reduce the incidence of false positive test results.

“Because of these favorable attributes, its operational simplicity, and the leveraging of existing technology, we predict that ADAP will provide a useful analytical platform for a multitude of clinical and research applications,” the authors conclude.

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.