Immune response develops in waves

How do we know how the immune response develops in untreated patients?

It is generally said that after a tick bite, the IgM response develops first, followed by the IgG response. The Health Protection Agency (HPA) states

“The chances of a positive test in early infection range from about 30% in the first two weeks to about 80% by six weeks, and the positivity rate increases further with duration of active infection.”

That implies a steady increase in antibodies, but HOW DO WE KNOW?

In an ideal world (for research purposes) one would want to follow individual patients before treatment, taking repeated blood tests over a period of months in order to study the immune response. That clearly cannot be done as it involves withholding treatment.

The next best is to study several patients with a known time between tick bite and the first blood sample. This is precisely what a recent German paper reports, and the results are very interesting.

This paper documents successive blood test results of a group of German patients with erythema migrans. A western blot was used, as the authors found it to be more sensitive than an ELISA test (which in itself is an interesting conclusion).

The first test was at a known period after a tick bite, ranging from 1 week to more than 10 weeks after the bite. The results show what appears to be an undulating early immune response, with IgM immune reaction peaking at 5 weeks, then declining and showing a second peak at week 9 before declining again.

Similarly, the IgG reaction showed a first peak at 4 weeks, a second peak at 8 weeks followed by another decline.

Of the patients first tested at more than 10 weeks post bite only 10% were IgM positive and 33% IgG positive. However, at only 4 weeks post bite 75% of patients had been IgG positive. This does not indicate a smooth increase in in antibodies.

The authors conclude:

“So, we suggest that a single serological finding is a snap shot and gives evidence of an infection. On the other hand, the true infection might be missed by negative immune response, as might be the case in about 40% seronegative EM patients.”

At the moment, in the absence of an erythema migrans (the characteristic rash which should always be treated regardless of test result) patients with, say, an equivocal test in early infection, followed by a negative test a few weeks later, would be unlikely to be given treatment unless they or their doctors persisted with further testing in the hope of getting a positive test. Given the confidence in the tests currently expressed by the HPA, that is unlikely to happen.

This research paper shows that we have to be much more careful when drawing conclusions from blood test results. Remember – only about half of patients see an erythema migrans and doctors are heavily reliant on test results.

What happens beyond 10 weeks? Does the immune response continue undulating?

Is a blood test always a snapshot?

The full paper is available on-line.