Sorting Through the Serum: A closer look at serologic tests

Type-specific serologic tests for herpes are highly sensitive and highly specific, but not entirely so. Why are serologic tests for
herpes not 100 percent accurate? As Rhoda Ashley Morrow, PhD, Professor of Laboratory Medicine at the University of Washington School of Medicine, explains, this is due to the nature of serum testing. “Antibodies are found in serum or in plasma, which has many other molecules, like albumin, other proteins, antibodies that are directed to other things.” The HSV antibodies in this mix are supposed to bind only with a target found in the test. “You can image something shaped liked a Y just kind of bouncing around trying to hook up and latch on to its antigen target.”

“Type-specificity,” or the ability distinguish between antibodies to HSV-1 and antibodies to HSV-2, is conferred by including a very limited, specialized set of antigens in each test. “Specificity” as a performance measure means conditions of the test don’t allow anything to bind or register except the antibody you are testing for. To ensure that other elements in this “sticky” serum don’t get caught up in the test and provide a false positive result, test manufacturers dilute the serum. As a result, Dr. Morrow notes, “you have fewer antibodies around, available to hook up with the target, and that can reduce sensitivity. It’s a balance. The more sensitive you make the test, the more problems you’re going to have with false positives (low specificity).”

Despite these inherent limitations, currently available serologic tests remain highly accurate. While there are some advances in herpes testing technology reflected in the tests now available on the market, the new technology does not change the testing landscape a great deal. “All of these tests–new high throughput formats and standard ELISAs–are going to have the same issues of a few false positives, a few false negatives, and the varying length of time individuals take to seroconvert,” Dr. Morrow notes. “All the FDA approved type specific tests for IgG to HSV-1 and HSV-2 actually do perform quite well.”

Cathy Heitman Avatar