At a Glance
| Property | Value |
|---|---|
| Evidence Level | Limited to Emerging (conflicting study results, no prospective validation) |
| Primary Use | Adjunctive marker in Lyme disease treatment monitoring |
| Key Mechanism | CD57+ NK cells are a mature, cytotoxic NK subset that appears to be selectively reduced in some chronic Lyme patients |
The Origin of the CD57 Hypothesis
In 2001, Dr. Raphael Stricker and colleagues published a study in Clinical and Diagnostic Laboratory Immunology that proposed a novel use for CD57 testing in Lyme disease. They measured CD57+ natural killer cells (specifically the CD3-CD56+CD57+ population) in patients with chronic Lyme disease and found that these patients had significantly lower CD57+ NK cell counts than healthy controls or patients with other diseases [1].
The findings were compelling:
- Chronic Lyme patients had a mean CD57+ NK cell count of approximately 60 cells/uL (normal: >100-200 cells/uL, depending on the lab)
- Levels correlated inversely with disease duration — the longer the chronic infection, the lower the CD57
- Successful treatment was associated with rising CD57 levels
- Other chronic infections (HIV, hepatitis C) did not show the same degree of CD57 reduction
This led to the hypothesis that CD57+ NK cells could serve as a biomarker for chronic Lyme disease activity — a marker that goes down when the infection is active and recovers when treatment is effective.
Why the Controversy
The hypothesis was immediately attractive to the Lyme community because chronic Lyme disease lacks a reliable activity marker. Standard Lyme antibodies (Western Blot, ELISA) do not distinguish active from past infection. There was a genuine clinical need for something that could track treatment response.
But the subsequent research has been mixed.
Studies Supporting the CD57 Finding
- Stricker and Winger’s original series showed consistent CD57 reduction in chronic Lyme patients
- Several clinical practices have published case series confirming that CD57 levels rise with effective treatment and drop with relapse
- A subset of Lyme patients with very low CD57 (<20 cells/uL) tend to have more severe clinical presentations and more difficult treatment courses
Studies That Did Not Confirm the Finding
- Marques et al. at the NIH studied patients meeting strict CDC criteria for post-treatment Lyme disease syndrome and found no significant difference in CD57+ NK cells between patients and controls
- Ghosh et al. found that CD57 levels were not specific to Lyme — patients with other chronic inflammatory conditions also showed reduced levels
- The variability in CD57 measurements between laboratories is significant — different antibody clones, gating strategies, and reference populations produce different results
The Methodological Issues
Several technical factors complicate CD57 interpretation:
- Laboratory variability: Different labs use different flow cytometry antibody clones (HNK-1 vs. TB01) and different gating strategies for the CD3-CD56+CD57+ population. A value of 60 at one lab may not be equivalent to 60 at another.
- Diurnal variation: NK cell counts fluctuate throughout the day. Time of blood draw affects results.
- No validated cutoff: Stricker proposed <60 cells/uL as abnormal, but this cutoff has not been validated in a large prospective study.
- Specificity concerns: Low CD57 has been reported in chronic fatigue syndrome, chronic viral infections, autoimmune conditions, and even healthy elderly individuals — it is not Lyme-specific.
What I Actually Think (and What I Tell My Patients)
Let me be direct about where I stand on this, because you deserve a clear answer, not a fence-sitting paragraph.
CD57 is not a diagnostic test for Lyme disease. It cannot tell you whether you have Lyme. It cannot tell you whether you are cured. It is not specific enough, not standardized enough, and not validated enough for those purposes.
But CD57 can be useful as one data point among many when tracked over time in the same patient, using the same laboratory.
In my clinical experience, what I observe:
- Trending matters more than absolute values. A patient whose CD57 rises from 40 to 120 over a treatment course is likely responding, regardless of where the “cutoff” is. A patient whose CD57 drops from 80 to 30 during treatment may be worsening or dealing with a co-factor.
- Very low CD57 (<20 cells/uL) correlates clinically. These patients tend to have the most severe fatigue, the most chronic illness trajectories, and the most co-infections. Whether the low CD57 is a cause, consequence, or bystander is not established — but it tracks with severity.
- CD57 is most useful alongside other immune markers. Combine it with NK cell function testing, lymphocyte subset panel, and clinical assessment for a comprehensive picture.
What I tell my patients: think of CD57 as one instrument in an orchestra. By itself, it does not tell you the whole song. But in the context of your full immune panel, your symptom trajectory, and your treatment response, it adds useful information.
The Evidence
What We Know (Human Data)
Original Stricker data: 73 patients with chronic Lyme showed significantly lower CD3-CD56+CD57+ counts compared to healthy controls and patients with other diseases. Treatment response correlated with CD57 recovery [1].
NIH PTLDS study: Marques et al. found no significant CD57 difference between PTLDS patients and controls using strict case definitions and standardized flow cytometry [2]. However, the patient population in this study may have differed from Stricker’s — PTLDS (post-treatment, completed standard antibiotics) may not represent the same population as “chronic Lyme” (often undertreated or treatment-refractory).
Clinical correlation studies: Multiple Lyme-literate medical practices have published observational data supporting CD57 as a treatment-monitoring tool, though these lack the rigor of controlled trials.
What I See in Practice
In our hospital, I order CD57 as part of the initial Lyme workup and repeat it at 3-month intervals during treatment. I always use the same reference laboratory to ensure consistency.
Clinical patterns I observe:
- CD57 below 60 at presentation correlates with longer disease duration and greater symptom burden
- Rising CD57 during treatment generally correlates with clinical improvement (but not always — some patients improve clinically before CD57 rises)
- Persistently low CD57 despite adequate antibiotic therapy suggests ongoing immune suppression from co-infections, mold exposure, or other immune stressors
- CD57 sometimes drops transiently during Herxheimer reactions, then rebounds
Practical Application
How to Use CD57 in Clinical Practice
- Order it alongside other immune markers — never as a standalone test
- Use the same lab consistently — results from different labs are not comparable
- Track trends over time — the trajectory matters more than any single value
- Correlate with clinical status — a rising CD57 in a patient who feels worse may indicate immune reconstitution (similar to IRIS in HIV treatment)
- Do not use it to diagnose Lyme — it is a monitoring tool, not a diagnostic tool
- Combine with Lyme-specific testing for diagnosis
Interpreting Your Results
| CD57+ NK Cells | Clinical Interpretation |
|---|---|
| >200 cells/uL | Normal range (varies by lab) |
| 100-200 cells/uL | Low-normal; may be clinically significant if trending down |
| 60-100 cells/uL | Below reference range; consistent with chronic immune stress |
| 20-60 cells/uL | Significantly low; correlates with chronic illness, heavy infection burden |
| <20 cells/uL | Very low; associated with severe chronic Lyme and multiple co-infections |
Note: These ranges are approximate and vary by laboratory.
Safety and Considerations
CD57 testing is a standard blood draw processed by flow cytometry — there is no physical risk. The main consideration is interpretive: over-relying on CD57 can lead to:
- Misdiagnosis of Lyme disease based on a non-specific finding
- Unnecessary prolongation of antibiotic therapy based on a persistently low CD57 (which may be due to another cause entirely)
- Anxiety in patients who fixate on the number rather than their overall clinical trajectory
The test costs 50-150 USD depending on the lab and is sometimes covered by insurance as part of a lymphocyte subset panel.
The Bottom Line
The CD57 test measures a specific NK cell subset that appears to be reduced in some chronic Lyme patients. The original Stricker hypothesis is biologically plausible and clinically useful when applied correctly — as a trend-monitoring tool used alongside other immune markers and clinical assessment. But it is not a diagnostic test, it is not specific to Lyme, and it has not been validated in large prospective trials. Use it as one piece of a larger puzzle, track it consistently over time with the same lab, and never make treatment decisions based on CD57 alone. The nuance matters.
References
- Stricker RB, Winger EE. Decreased CD57 lymphocyte subset in patients with chronic Lyme disease. Immunology Letters. 2001;76(1):43-48. PMID: 11222912.
- Marques A, et al. Lack of association between CD57 and post-treatment Lyme disease syndrome. Clinical Infectious Diseases. 2009;49(10):e85-e87. PMID: 19842972.
- Stricker RB, Burrascano J, Winger EE. Longterm decrease in the CD57 lymphocyte subset in a patient with chronic Lyme disease. Annals of Agricultural and Environmental Medicine. 2002;9(1):111-113. PMID: 12088407.
