“The myth of the exact cut-off”

cut offsImmunological cut-off values have been the subject of some discussion in our lab recently and it got me thinking (which is unusual & noteworthy in itself…).

For Infectious disease X, an exact cut-off antibody level of what constitutes immunity is a myth, which is somehat sustained by peer pressure to provide such a result.

For example let’s say the cut-off antibody level for immunity to Disease X is quoted at 10 iu/ml. Does this mean that the patient with an antibody level of 9iu/ml must be non-immune (and be a candidate for vaccination if available), whereas the patient with an antibody level of 11iu/ml is definitely immune?

It doesn’t take a PhD in microbiology to realise that this is a bit of a nonsense. There are so many other factors that dictate whether a person might be immune to Disease X or not. The general immunity of the patient, the infecting dose of organism X are obvious starters, not to mention the natural margin of error of the laboratory assay itself. No amount of research is ever going determine an exact antibody level for immunity to Disease X…

So why do we continue to report exact cut-offs?

It is probably because it is what the requestor wants. The requestor does not want a vague nebulous uncertain answer, even if this is the truth of the matter. The requestor wants to know whether the patient is immune or not immune, end of story.

Do we need to change how we report immune cut-offs?

Grey zones alleviate the problem to some extent in that we can at least relay some of the uncertainty back to the requestor. A lot of laboratories have inserted “Grey zones” to at least partially solve the problem of Immune cut-offs.

I think from the laboratory point of view it is important to relay to the requestor that determining someone’s immune status is a fairly inexact science. They also need to be aware that the laboratory result we provide is only a guide really and needs to be interpreted with a large degree of caution, regardless of whether we label it Immune, Non-immune or Grey Zone….


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