1. Recent infection before immune response

  2. Antibodies are in immune complexes

  3. Spirochete encapsulated by host tissue (i.e.: lymphocytic cell walls)

  4. Spirochete is deep in host tissue (i.e.: fibroblasts, neurons, etc.)

  5. Blebs in body fluid, no whole organisms needed for PCR

  6. No spirochetes in body fluid on day of test

  7. Genetic heterogeneity (300 strains, 100 in U.S.)

  8. Antigenic variability

  9. Surface antigens change with temperature

  10. Utilization of host protease instead of microbial protease

  11. Spirochete in dormancy phase (L-form) with no cell walls

  12. Recent antibiotic treatment

  13. Recent anti-inflammatory treatment

  14. Concomitant infection with babesia may cause immunosuppression

  15. Other causes of immunosuppression

  16. Lab with poor technical capability for Lyme disease

  17. Lab tests not standardized for late stage disease

  18. Lab tests labeled "for investigational use only"

  19. CDC criteria is epidemiological not a diagnostic criteria

  20. Lack of standardized control

  21. Most controls use only a few strains as reference point

  22. Few organisms are sometimes present

  23. Encapsulated by glycoprotein "S-layer" which impairs immune recognition

  24. "S"- layer binds to IgM

  25. Immune deficiency

  26. Possible down regulation of immune system by cytokines

  27. Revised W.B. criteria fails to include most significant antigens