Once Seronegative, Always Seronegative??

I have read from reputable sources that around 20% of people infected with lyme and confirmed by other means( bulls eye rash, culture etc) never produce the expected antibodies that would be required to test positive via serology.

I haven't found the official study that reported this as yet.

So if anyone has a reference i would be interested.

It is a sad paradox for many potential patients. Many times the sickest are denied treatment because mainstream testing fails to detect Lyme antibodies, only because they are so immunocompromised. It is indeed a vicious cycle...

I just did a PubMed search for "Seronegative Lyme disease". It came back with 208 published papers or letters on this subject. One is even entitled Seronegative Lyme disease.  Most have abstracts that provide the most important information from the study. Some letters have no abstract. about 20% let you download a PDF for free. The others you have to pay for. In the list produced the ones that are free say so.

https://pubmed.ncbi.nlm.nih.gov/

A common cause of seronegative Lyme disease is antibiotic therapy that was not Curative. Also some people don't take their antibiotics properly. I talked to a man extremely badly affected who admitted to missing doses. And then his wife chimed in honey there were entire days where you missed both doses.

Serologic tests are targeted at the antibodies we produce To fight off the infection. Antibodies are made by B-cells. These antibodies take time to build up In a process called Affinity maturation. T white cells stimulate the B cells to make the Antibodies. For Affinity maturation To complete ongoing T-cell stimulation is required. Non-curative antibiotics will rid the body of nearly all spirochetes and the Affinity maturation process breaks down and the patient will be in most cases permanently seronegative unless they get a new infection with a different strain.

Another cause of negative serologic tests is if the strain you are infected with is different enough From The Strain used to create the test.

Here is the most relavant information From the seronegative Lyme disease paper.

https://pubmed.ncbi.nlm.nih.gov/3054554/

On Western blot analysis, the level of immunoglobulin reactivity against B. burgdorferi in serum from these patients was no greater than that in serum from normal controls. The patients had a vigorous T-cell proliferative response to whole B. burgdorferi, with a mean ( +/- SEM) stimulation index of 17.8 +/- 3.3, similar to that (15.8 +/- 3.2) in 18 patients with chronic Lyme disease who had detectable antibodies. The T-cell response of both groups was greater than that of a control group of healthy subjects (3.1 +/- 0.5; P less than 0.001). We conclude that the presence of chronic Lyme disease cannot be excluded by the absence of antibodies against B. burgdorferi and that a specific T-cell blastogenic response to B. burgdorferi is evidence of infection in seronegative patients with clinical indications of chronic Lyme disease.

there is some evidence that other strains do not necessarily have the same outer membrane proteins as the lab strain B31 - isolated from a tick found in the USA (that grows nicely in the lab - but was not actually found in a human) that the majority of commercial tests are based on.

in the UK / Europe - they still seem to use tests based on this B31 strain - even though the majority of cases in UK and Europe ( 60-70%) are actually caused by Borrelia Garinii or Borrelia Alfzelli - so that logic seems very strange.

i was negative several times on ELISA and Western Blot via the standard UK NHS tests - but then clearly positive on both IgG and IgM in a test at Armin that used proteins from B.Garinii ( the TickPLex test made by Finnish company Tezted)

also - there are studies describing how borrelia preferentially infect and damage the germinal centres in the host early in the course of the infection. this is important because the handover between T-cells and B-cells that Peter describes - and the selection of antibodies that follows - actually takes place inside these germinal centres - so this could well be another explanation for why some people never produce expected antibodies.

i remember reading - i think on LymeDidease.org that they think 20% of people are in this category - infected but never produce antibodies. they are usually pretty good at sticking to what we have evidence for and referencing their articles - but i don't think i ever found the source for this statement.

overall I'm not sure if its the case that people are deliberately designing or using tests that are inaccurate - i think its probably just more likely that serologic tests for chronic infections are unreliable in the first place - and then the test designers are assuming its a rare disease when they set the thresholds - but there are some studies in older people in Europe that show over 50% have antibodies to borrelia - and also the RED labs Phage test that published a paper showing around 50% of "healthy controls" actually had borrelia in them ( strictly speaking they detected bacteriophages that only live in borrelia in these people).

if you believe the reality is that few people are infected - when you design the test you set the positive threshold high enough to return a small number of positives.
if, in actual reality, many people are carrying the organism but kept under control buy their immune systems ( much like most microorganisms we encounter) - and with some level of antibodies - the above test will become pretty much a random number generator for most people.

RobWireGuy said...
Thanks Peter-Lyme for the in-depth explanation!
Sometimes I wonder that there may indeed be a new Bb species present in the Midwest, if not locally (Eastern Wisc.). Too many people locally are getting bit and getting sick, with very few serologically testing positive. I was recently bit (June) & have progressively become more symptomatic, but negative tests have prevented me from re-starting an ABX regimen. This has been the case with several people locally.........

Maybe it’s not borrellia. A Lyme test is only testing for borrelia. Maybe it’s a different infection. Are there commonalities in the symptoms people have been getting in your area?