CD 57

— update —

After posting the information below I discovered an additional article from 2000 by Stricker & Winger. They evaluated 73 patients with chronic lyme disease. Six of those patients were tested repeatedly over 4 months. They found significant differences between those with chronic lyme, and various comparison groups. This constitutes (I believe) better evidence than any of the other studies I cited. The findings contradict the conclusions below. I’m not sure what to think — it appears that knowledgeable Lyme literate medical experts have concluded that the CD57 is not trustworthy, yet this (early) study seems to indicate a big difference between groups. Here’s my understanding of what they did and found:

Sample:

  • 10 acute Lyme disease patients (within 1 month of a tick bite)
  • 22 patients with HIV and CD4 counts¬† < 200 / microliter
  • 73 patients with chronic lyme disease (huge variety in this sample: 3 months to 15 years sick; 31 hadn’t been treated and 42 were in or post treatment; 48 had primarily musculo-skeletal symptoms and 20 had primarily neurological symptoms). Of these, 6 were tested repeatedly over 4 months and 1 was followed for 9 years

Results

  • pre treatment 100% had abnormal cd57 counts; during treatment 50% did; post treatment 0% did (difference from pre treatment significant: p < .001)
  • acute LD 0% had abnormal cd57 counts; HIV 18% had abnormal cd57 counts. Both groups differ significantly from the pre treatment lyme group.
  • those with musculo-skeletal symptoms had higher cd57 counts (average = 58) than those with primarily neurological symptoms (average = 30); this difference is significant (p = .002), both groups improved during treatment.
  • in the 6 tested >2 times, 4 had clinical improvement (and all doubled their CD57 counts or more) and two did not (and their counts stayed low). The patient who was followed for 9 years had persistent symptoms and persistent low CD57 counts. This case was in submission and probably corresponds to reference [2] below.

Absent the testimonials below, this seems to be fairly convincing evidence that the CD57 count is meaningful. I’m very curious to hear any explanations for the differences in opinion here, and I don’t believe my medical knowledge is sufficient to judge them.

— end of update —

Some investigative blogism seems in order as I’ve just been given a new test (the CD57, also known as the Stricker NK panel) and need to understand how to interpret it. I’ll start by summarizing what I found: Although CD57 is biologically associated with Lyme disease CD57 cells are not a reliable clinical marker for the level of disease in chronic lyme patients, although C4a cells (according to Savely) and/or the vitamin D reversal pattern (according to LymeMD) may be (hopefully I will get a chance to investigate those in future posts). That’s not to say that CD57 has no meaning, only that it’s not as straightforward to interpret, on average, as we would like. Here is my summary of the literature on CD57 to back up the statements made in this paragraph. I’ll start by trying to explain what the CD57 measures, and then I’ll discuss the clinical and medical evidence that it is not a valid marker for Lyme.

There are two summaries available online that try to explain what the CD57 cells are (one by Ginger Savely, R.N. who says elsewhere that it is not a reliable clinical marker, and one by LymeMD who says that in his experience the CD57 count has not been a good indicator of the needs of his patients). Free Ideas’ summary of other’s opinions about the CD57 leads to the same conclusions: don’t trust the CD57. It also includes a great illustration of how T-cells work.

Despite the skepticism of the bloggers mentioned above, the summaries are pretty accessible. Basically, they say that CD57 cells are a type of white blood cell. White blood cells, and specifically lymphocytes, are one way the body fights off infection. CD57 cells are type of lymphocyte, natural killer T cells. When the body is fighting and infection (such as Lyme disease), the number of natural killer T cells increases. Most of these are CD 56 cells, but a smaller subset has the CD 57 marker. The presence of CD57 cells can be measured using flow cytometry.

But why should we care about CD57 cells? According to Focosi & Petrini (2007), CD57 cells increase naturally with age and with¬† diseases “associated with immune dysfunction” including conditions like multiple myeloma and rheumatoid arthritis as well as infectious diseases such as HIV, CMV, TB & Lyme (but they cite the Stricker & Winger papers (2002 & 2003) which argue that the CD57 count decreases with Lyme, so their statement is a little hard to interpret).

So what, exactly, is the evidence that CD57 cells might be a good measure of how ill someone is with Lyme disease? There are three published works that deal explicitly with the prevalence of CD57 in Lyme disease ([1, 2, 3] below). Two are longitudinal but anecdotal at best in the quality of their evidence ([1 & 2]). Stricker & Winger, 2003 present a case study of two patients with neurological Lyme with the unusual symptom of musical hallucinations. Over the course of 8 months, both patients were treated with oral and then IV antibiotics. One patient showed increased CD57 counts (she had received significant prior antibiotic therapy and began with a normal CD57 count). The other patient did not, and also only received temporary relief from her symptoms. Stricker, Burrascano & Winger (2002) is a case study of one patient over a 10 year period, who experienced consistently depressed CD57 levels. Marques, Brown & Fleischer (2009) is a sample study, meaning they gathered information from a much larger number of people, allowing it to use statistical tests to compare them. It finds no significant difference between those with lyme disease (divided into “post lyme syndrome” and “recovered”) and healthy volunteers. All three groups have a large range, and the means and standard deviations overlap a lot. This last study is to be trusted more than the longitudinal case studies because it looks at more people, however it tells us nothing about how CD57 levels change over time.

So here’s my summary: While CD57 cells are part of the immune system, and therefore have some relationship to how it is functioning, there is no clear information about whether they are associated at all with level of illness in Lyme disease [1, 2, 3]. The available data tells even less about possible cause and effect. However, although it is mentioned in the Burrascano guidelines as a possible measure of infection, there are two respected lyme literate healers (a doctor and a nurse) who have blogged independently about its unreliability (mentioned above). In the end, all we know for sure is that CD57 counts may be affected by infection [4], as well as age [4]. How they are affected, or what we can learn from that, is hard to say. I plan on looking elsewhere for quantitative measures of how my disease is progressing.

[1] Stricker R. B. & Winger, E. E. (2003). Musical hallucinations in patients with lyme disease. Case report, Southern Medical Journal, 96(7):711-715. (html version)

[2] Stricker, R. B., Burrascano, J. J. & Winger, E. E. (2002). Longterm decrease in the CD57 lymphocyte subset in a patient with chronic lyme disease. Case report, Ann Agric Environ Med, 9:111-113. (pdf)

[3] Marques, A., Brown, M. R., Fleisher, T. A. (2009). Natural killer cell counts are not different between patients with post-Lyme disease syndrome and controls. Clinical Vaccine Immunology. 16(8):1249-1250. (doi:10.1128/CVI.00167-09)

[4] Focosi, D. & Petrini, M. (2007). CD57 expression on lymphoma microenvironment as a new prognostic marker related to immune dysfunction. Journal of Clinical Oncology. 25(10):1289-1291. (DOI: 10.1200/JCO.2006.10.2251)

5 Comments

  1. SeaStar said,

    November 8, 2011 at 12:12 am

    Thank you for your thorough and candid review of the literature. I have been trying to make sense of all this myself.

  2. jmankoff said,

    November 8, 2011 at 10:20 am

    glad to help!

  3. Leens said,

    August 30, 2013 at 7:56 am

    Thank you for this unbiased perspective. I myself am a bit skeptical of how much weight to put on the CD57. I had a rash a few months ago, a positive ELYSA and 2 bands on the western blot show up with minor symptoms (no prior symptoms and a normal, healthy pregnancy a year prior). Because I have had friends with chronic Lyme they urged me to see an LLMD for preventative measures after I was treated with 3 weeks of doxy. The LLMD ran some more tests that came back negative for organisms and coinfections. The only abnormalities was my CD57 was a 45 and I had a very small vitamin D deficiency (just missed the cut off of normal). Because of this CD57 the LLMD told me this is not a new infection but a reinfection going back 8-10 years! I have had to do research on my own to figure out that there is no way for anyone to tell that, especially because I was asymptomatic of classic Lyme features until my rash appeared a few months ago! This has been a very confusing and upsetting process to say the least because there are no definitive answers and only 2 extreme sides to Lyme. I can’t seem to find anyone in the middle. I am currently on long-term Rifampin because of this CD57 and very slight symptoms that I’m not sure are even attributed to Lyme. Also on hydroxychloroquine just in case for cyst form and some other herbals and supplements. Not sure if I want to continue on abx anymore. Thanks for listening!

  4. jmankoff said,

    September 2, 2013 at 9:21 am

    It’s great that you were negative for co-infections, etc. I am surprised by the specificity of you’re doctors interpretation of the test results. I wonder whether it’s worth getting a second opinion from another LLMD? You are the best judge of whether you feel sick or not. Personally, I find it just as problematic to be told it’s all in my head when I feel ill, as to be told I’m sick when I feel healthy :).

  5. Majbrit said,

    February 7, 2014 at 8:02 am

    Maybe Leens your pregnancy has also caused the low CD 57 cell count. I have a low cell count because of chlamydia plaumonia that I have had for 20 years with out knowing it. When I then had a tick bite I had no chance of fighting the infektion on my own. I guess that my pregnancy, my chlamydia p, my mycoplasma and lyme all explaines the low CD 57 and why I have such a difficult time getting well. Now I am doing anything to make my immune system stronger. It takes a long time to improve the immune system my doctor told me.


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