Your patient has a positive IgM anti-Herpes Simplex virus serology. What does it mean? Could it be a false positive?

Serology tests for HSV have improved dramatically in the past ten years. The antigen preparations used by manufacturers are better defined and often use recombinant or other highly purified antigens. Further, the availability of independent proficiency testing from agencies like CAP and API provide objective information about performance of the tests by a wide variety of laboratories. A few years ago, the tests for IgG anti-HSV types 1 and 2 often cross-reacted to such an extent that one could not reliably distinguish between these two types with that test. However, the FDA-approved assays currently in use are able to make this distinction with IgG.

Despite these improvements, serology testing for HSV is not perfect. Antibodies formed against other viral antigens may cross-react with even highly purified HSV in current serology screening tests. Further, currently available IgM anti-HSV kits do not consistently distinguish between HSV types 1 and 2. So what should you do?

The key is to correlate the clinical situation with the type of antibody found, occasionally do repeat testing and whenever in doubt call our laboratory and speak to one of our doctoral scientists who are expert in this type of testing.

IgM antibodies specific for HSV are present only for a relatively short period of time. They are the first antibodies to form after the infection, and as such are excellent markers for the presence of recent or active clinical disease. They may also be found in serum from 10-30% of patients who have reactivation of a previous herpes infection. IgM antibodies against HSV usually begin to form within 1-2 weeks after onset of the infection. The IgM antibody response usually declines rapidly such that after a few weeks or months (depending on the infection) they are undetectable. In contrast, IgG antibodies form more slowly, but persist for months or years.

Early on during an infection one would expect to see IgM antibodies with little, if any IgG antibodies. Clinically, there should be some evidence of HSV in many cases at this early stage. Therefore, a positive IgM anti-HSV in a child with recent cold sore vesicles helps to confirm the infection by Herpes Simplex Virus. If there is no clinical evidence of disease and the test was being used as a screening test, a repeat assay should be performed in 2-3 weeks. During that time, the IgG response would normally become predominant. If only an IgM anti-HSV is present with no development of IgG and no clinical history of disease a false positive IgM result should be suspected. We recommend that you call us directly about such unusual cases. After reviewing the case with you, we may be able to make suggestions about additional testing that could help to clarify the issue.

The handy virology chart that Dr. Dan Wiedbrauk provided in the last issue of the Warde Report may be useful in reviewing the likely clinical symptoms associated with a variety of viral infections and the type of specimens to submit for optimal results. Click to view the Virology Ordering Guidelines chart or if you prefer, just call our client services department at 800 876-6522 and we’ll be glad to send you a copy.

Serology is not yet a perfect mechanism to test for infectious diseases. However, when the specific antibodies are correlated with the clinical picture, history of vaccinations and presence of IgM and/or IgG antibodies, it will usually provide clinically useful information. However, whenever you have a question or concern about an assay, please feel free to call us.