SERONEGATIVE LYME DISEASE

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