Just as much as with reading bacterial culture plates, there is art in serology. I am not saying that the results should be created from thin air, more that the interpretation of serology results needs to handled very carefully. I think you learn to get a feel for when a result is right or wrong, which is not very scientific really.
I usually say that serology is half result, half interpretation. Knowledge of sensitivity, specificity and positive predictive value are key.
There are (quite) a few ways in which serological results can lead us up the garden path:
- Cross-reactivity. The truth is that any serological test can cross-react and give a false positive result. The most common scenarios however are when testing for Herpeviruses or Arboviruses. Over the past few months, I have seen quite a few cases of false positive CMV IgM results due to cross reaction from EBV antigens circulating in the patient. This may not be that important in an infectious mononucleosis illness in a fit healthy young adult, but a false positive diagnosis of CMV is much more critical in pregnancy. I now think twice before releasing a positive CMV result before knowing the EBV serology status.
- Prolonged presence of IgM. Toxoplasma is the classical example of this, with IgM persisting for up to two years after the initial infection.
- Rapid appearance of IgG. My impression of the sophisticated and sensitive assays that we use nowadays is that IgG can be picked up almost as quickly as IgM. We really need to throw the rather misleading textbooks out the window when it comes to both appearance and duration of IgM and IgG.
- Geographically specific serotypes. Make sure that the serotypes that your serology assay looks for actually occur in your locality. Leptospirosis assays are a good example of this.
- Low reactive results. Some sort of serological reaction is picked up by the EIA but is insufficient to meet the criteria of being positive. What do these mean and how are they interpreted?
Generally clinicians regard laboratory results as “the gospel truth” without particular regard to the multiplicity of factors, including those above which can render them dubious, most of which are outwith our control.
This demonstrates therefore the importance of appropriate comments (which I call disclaimers) attached to serological results, to show that although we think this result is correct, one can never be totally sure with serology….