Novel diagnosis of lyme disease: Potential for CAM intervention

Evidence-based Complementary and Alternative Medicine

Volumn 6, Issue 3, 2009, Pages 283-295

  Vojdani, Aristo ^a   Hebroni, Frank ^b   Raphael, Yaniv ^c   Erde, Jonathan ^b   Raxlen, Bernard ^d  

^a Immunosciences Laboratories Inc   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^d Raxlen Clinic   (United States)

Author keywords

Borrelia burgdorferi; In vivo induced antigen technology; Lyme disease; Multi peptide ELISA

Indexed keywords

AMOXICILLIN PLUS CLAVULANIC ACID; ANTIBIOTIC AGENT; AZITHROMYCIN; BACTERIAL ANTIGEN; BACTERIAL PROTEIN; BOSWELLIA SERRATA EXTRACT; CAPSAICIN; CEFTRIAXONE; CEFUROXIME AXETIL; CLARITHROMYCIN; DOXYCYCLINE; ERYTHROMYCIN; GINKGO BILOBA EXTRACT; HERBACEOUS AGENT; HYDROXYCHLOROQUINE; IMIPENEM; IMMUNOGLOBULIN G ANTIBODY; IMMUNOGLOBULIN M ANTIBODY; METRONIDAZOLE; MINOCYCLINE; NUTRACEUTICAL; OMEGA 3 FATTY ACID; PENICILLIN G; QUERCETIN; RIFAMPICIN; SALIVA PROTEIN; SALIVARY PROTEIN 15; TAUROX SB; UBIDECARENONE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANCOMYCIN;

ACCURACY; ALTERNATIVE MEDICINE; ANTIBIOTIC THERAPY; ANTIBODY PRODUCTION; AUTOIMMUNITY; BACTERIAL VIRULENCE; BORRELIA BURGDORFERI; CLINICAL FEATURE; DIAGNOSTIC PROCEDURE; ENZYME LINKED IMMUNOSORBENT ASSAY; HUMAN; IN VIVO INDUCED ANTIGEN TECHNOLOGY; LYME DISEASE; NONHUMAN; PATHOGENESIS; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; REVIEW; SENSITIVITY AND SPECIFICITY; TICK BORNE DISEASE; WESTERN BLOTTING;

EID: 68849084276     PISSN: 1741427X     EISSN: 17414288     Source Type: Journal    
DOI: 10.1093/ecam/nem138     Document Type: Review

References (97)

1. Steere AC, Grodzicki RL, Kornblatt AN, Craft JE, Barbour AG, Burgdorfer W, et al. The spirochetal etiology of Lyme disease. N. Engl. J. Med. 1983;308:733-740
2. Steere AC. Lyme disease. N. Engl. J. Med. 1989;321:586-596
3. Kantor FS. Disarming Lyme disease. Scientific American 1994;271:34-39
4. Bock SJ. The integrative treatment of Lyme disease. Int. J. Integ. Med. 1999;1:19-23.
5. Howenstine J. New ideas about the cause, spread and therapy of Lyme disease. Townsend Letter for Doctors 2004;252:64-67
6. Dattwyler RJ, Volkman DJ, Coanty SM, Platkin SP, Luft BJ. Amoxicillin plus probenecid versus doxycycline for treatment of erythema migrans borreliosis. Lancet 1990;336:1404-1406
7. Luger SW, Paparone P, Wormser GP, Nadelman RB, Grunwaldt E, Gomez G, et al. Comparison of cefuroxime axetil and doxycycline in treatment of patients with early Lyme disease associated with erythema migrans. Antimi crob. Agents Chemother. 1995;39:661-667
8. Nicolson GL. Diagnosis and therapy of chronic systemic co-infections in Lyme disease and other tick-borne infectious diseases. Townsend Letter 2007;93-98
9. Gardulf A, Wolfhart I, Gustafson R. A prospective crossover field trial shows protection of lemon eucalyptus extract against tick bites. J. Med. Entemol. 2004;41:1064-1067
10. Tikka TM, Koistinaho JE. Minocycline provides neuroprotection against N-methyl-D-aspartate neurotoxicity by inhibiting microglia. J. Immunol. 2001;166:7527-7533
11. Hoyt JC, Ballering J, Numanami H, Hayden JM, Robbins RA. Doxycycline moderates nitric oxide production in murine lung epithelial cells. J. Immunol. 2006;176:562-572 (Pubitemid 43023304)
12. Du C, Khalil MW, Sriram S. Administration of dehydroepiandrosterone suppresses experimental allergic encephalomyelitis in SJL/J mice. J. Immunol. 2001;167:7094-7101 (Pubitemid 33144206)
13. Spach KM, Nashold FE, Dittel BN, Hayes CE. IL-10 signaling is essential for 1, 25-dihydrooxyvitamin D3-mediated inhibition of experimental autoimmune encephalomyelitis. J. Immunol. 2006;177:6030-6037
14. 2 synthesis. J. Immunol. 2006;176:111-117
15. Schreibert G, Musters RJP, Reijerkerk A, de Groot LR, van der Pol Hendricx EML, Dopp ED, et al. Lipoic acid affects cellular migration into the central nervous system and stabilizes blood-brain barrier integrity. J. Immunol. 2006;177:2630-2637 (Pubitemid 44201022)
16. Targoni OS, Tary-Lehmann M, Lehman PV. Prevention of murine EAE by oral hydrolytic enzymes. J. Autoimm. 1999;12:191-198 (Pubitemid 29223050)
17. Mynott TL, Ladhams A, Scarmato P, Engwerda CR. Bromelain from pineapple stems proteolytically blocks activation of extracellular regulated kinase-2 in T cells. J. Immunol. 1999;163:2568-2575 (Pubitemid 29399179)
18. Beltran J, Ghosh AK, Basu S. Immunotherapy of tumors with neuroimmune ligand capsaicin. J. Immunol. 2007;177:3260-3264 (Pubitemid 46333209)
19. Kim HY, Park EJ, Joe EH, Jou I. Curcumin suppresses Janus kinase-stat inflammatory signaling through activation of Src homology 2 domain-containing tyrosine phospatase 2 in brain microglia. J. Immunol. 2003;171:6072-6079 (Pubitemid 37467228)
20. Gururajan M, Dasu T, Shahidain S, Jenning CD, Robertson DA, Rangnekar VM, et al. Spleen tyrosine kinase, a novel target of curcumin is required for B lymphoma growth. J. Immunol. 2007;178:111-121 (Pubitemid 46033592)
21. Nair MP, Mahajan S, Reynolds JL, Aalinkeel R, Nair H, Schwartz SA, et al. The flavonoid Quercetin inhibits proinflammatory cytokine TNF-α gene expression in normal peripheral blood mononuclear cells via modulation of NF-KB system. Clin. Vaccine Immunol. 2006;13:319-328
22. Lin H, Cheung SWY, Nesin M, Cassileth BR, Cunningham Rundles S. Enhancement of umbilical cord blood cell hematopoiesis by mitake beta-glucan is mediated by granulocyte colony-stimulating factor production. Clin. Vaccine Immunol. 2007;14:21-27
23. Di Giacinto C, Marinaro M, Sanchez M, Strober W, Boirivant M. Probiotics ameliorate recurrent TH1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-β-bearing regulatory cells. J. Immunol. 2005;174:3237-3246 (Pubitemid 40354026)
24. Arthur S. The effectiveness of Samento, Cumada, Burbur and Drl Lee Cowden's protocol in the treatment of chronic lyme disease. Townsend Letter 2007;101-106
25. Duke JA. Herbs with anti-Lyme potential. Townsend Letter 2007;114-117
26. Vojdani A, Erde J. Regulatory T cells, a potent immunoregulatory target for CAM researchers: The ultimate antagonist (I). eCAM 2006;3:209-215
27. Vojdani A, Erde J. Regulatory T cells, a potent immunoregulatory target for CAM researchers: Modulating allergic and infectious disease pathology (II). eCAM 2006;3:1-6.
28. Vojdani A, Erde J. Regulatory T cells, a potent immunoregulatory target for CAM researchers: Modulating tumor immunity, autoimmunity and alloreactive immunity (III). eCAM 2006;3:309-316 (Pubitemid 44310274)
29. Rosenbaum M, Vojdani A, Susser M, Watson CM. Improved immune activation markers in chronic fatigue and immune dysfunction syndrome (CFIDS) patients treated with thymic protein A. J. Nutrit. Environ. Med. 2001;11:241-247
30. Chu D, Wong WL, Mavligit GM. Immunotherapy with Chinese medical herbs I. Immune restoration of local xenogenic graft-versus-host reaction in cancer patients by fractionated astragalus membranaceous invitro. J. Clin. Lab. Immunol. 1988;25:119.
31. Schmidt BL. PCR in laboratory diagnosis of human Borrelia burgdorferi infections. Clin. Microbiol. Rev. 1997;10:185-201.
32. Vojdani A, Raxlen BT. Simultaneous measurement of antibodies against Borrelia, Babesia and Ehrlichia by Western Blot and multipeptide ELISA. FASEB J. 2005;19:95, Abstract.
33. Vojdani A. Part 1: In vivo-induced antigen technology: the most sensitive method of detection for Lyme disease and other tick-borne diseases. Townsend Letter 2007;285:107-113
34. Vojdani A. Part 2: The use of lymphocyte proliferation assay and cytokine production in seronegative patients with Lyme arthritis or neuroborreliosis. Townsend Letter 2007;286:104-111
35. Rauter C, Mueller M, Diterich I, Zeller S, Hassler D, Meegans T, et al. Critical evaluation of urine-based PCR assay for diagnosis of Lyme borreliosis. Clin. Diag. Lab. Immunol. 2005;12:910-917
36. Centers for Disease Control and Prevention. Recommendation for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. Morb. Mortal Wkly. Rep. 1995;44:590.
37. Luger SW, Krauss E. Serologic tests for Lyme disease: interlaboratory variability. Arch. Intern. Med. 1990;150:761-816.
38. Dressler F, Whalen JA, Reinhardt BN, Steere AC. Western blotting in the serodiagnosis of Lyme disease. J. Infect. Dis. 1993;167:392-400.
39. Engstrom SM, Shoop E, Johnson RC. Immunoblot interpretation criteria for serodiagnosis of early Lyme disease. J. Clin. Microbiol. 1995;33:419-427
40. Saah AJ, Hoover DR. "Sensitivity" and "specificity" reconsidered: the meaning of these terms in analytical and diagnostic settings. Ann. Intern. Med. 1997;126:91-94
41. Mahan MJ, Slauch JM, Mekalanos JJ. Selection of bacterial virulence genes that are specifically induced in host tissues. Science 1993;259:686-688 (Pubitemid 23066292)
42. Mahan MJ, Heithoff DM, Sinsheimer RL, Low DA. Assessment of bacterial pathogenesis by analysis of gene expression in the host. Annu. Rev. Genet. 2000;34:139-164
43. Rollins SM, Peppercorn A, Hang L, Hillman JD, Calderwood SB, Handfield M, et al. In vivo induced antigen technology (IVIAT). Cellular Microbiol. 2005;7:1-9.
44. Sung SY, McDowell JV, Marconi RT. Evidence for the contribution of point mutations to VlsE variation and for apparent constraints on the net accumulation of sequence changes in VlsE during infection with Lyme disease spirochetes. J. Bacteriol. 2001;168:5855-5861
45. McDowell JV, Sung S, Hu LT. Evidence that the variable regions of the central domain of VlsE are antigenic during infection with Lyme disease spirochetes infection and immunity. Infect. Immun. 2002;70:4196-4203
46. Magnarelli LA, Ijdo JW, Padula SJ, Flavell RA, Fikrig E. Serologic diagnosis if Lyme borreliosis by using enzyme-linked immunosorbent assays with recombinant antigens. J. Clin. Microbiol. 2000;38:1735-1739
47. Alitalo A, Meri T, Lankinen H, Seppala I, Lahdenne P, Hefty PS, et al. Complement inhibitor factor H binding to Lyme disease spirochetes is mediated by inducible expression of multiple plasmid encoded outer surface protein E paralogs. J. Irnmunol. 2002;169:3847-3853
48. Metts MS, McDowell JV, Theisen M, Hansen PR, Marconi RT. Analysis of the OspE determinants involved in binding of Factor H and OspE targeting antibodies elicited during Borrelia burgdorferi infection in mice. Infect. Immun. 2003;71:3587-3596
49. Crowley C, Huber BT. Host-adapted Borrelia burgdorferi in mice expresses OspA during inflammation. Infect. Immun. 2005;71:4003-4010
50. Gross DM, Forsthubert T, Tary-Lehmann M, Etling C, Ito K, Nagy ZA, et al. Identification of LFA-1 candidate autoantigen in treatment resistant Lyme arthritis. Science 1998;281:703-705 (Pubitemid 28390407)
51. Earnhart CG, Buckles EL, Dumler JS, Marconi RT. Demonstration of OspC type diversity in invasive human Lyme disease isolates and identification of previously uncharacterized epitope that defines the specificity of the OspC murine antibody response. Infect. Immun. 2005;73:7869-7877
52. Earnhart CG, Marconi RT. OspC phylogenetic analyses support the feasibility of a broadly protective polyvalent chimeric Lyme disease vaccine. Clin. Vaccine Immunol. 2007;14:628-634
53. Fingerle V, Goettner G, Gern L, Wilske B, Schulte-Spechtel U. Complementation of a Borrelia afzelii OspC mutant highlights the crucial role of OspC for dissemination of Borrelia afzelii in Ixodes ricinus. Int. J. Med. Microbiol. 2007;297:97-107.
54. Xu Q, McShan K, Liang FT. Identification of an OspC operator critical for immune evasion of Borrelia burgdorferi. Mol. Microbiol. 2007;64:220-231
55. Xu Q, Seemanapali SV, McShan K, Liang FT. Constitutive espression of outer surface protein C diminishes the ability of Borrelia burgdorferi to evade specific humoral immunity. Infect. Immun. 2006;74:5177-5184
56. Metts MS, McDowell JV, Theisen M, Hansen PR, Marconi RT. Analysis of the OspE determinants involved in binding of factor H and OspE-targeting antibodies elicited during Borrelia burgdorferi infection in mice. Infect. Immun. 2003;71:3587-3596
57. Crother TR, Champion CI, Whitelegg JP, Aguilera R, Wu XY, Blanco DR, et al. Temporal analysis of the antigenic composition of Borrelia burgdorferi during infection in rabbit skin. Inf. Immun 2004;72:5063-5072. (Pubitemid 39223390)
58. Philipp MT, Wormser GP, Marques AR, Bitker S, Martin DS, Nowakowski J, et al. A decline in C6 antibody titers occurs in successfully treated patients with culture-confirmed early localized or early disseminated Lyme borreliosis. Clin. Diag. Lab. Immunol. 2005;12:1069-1074
59. Wallich R, Pattathu J, Kitiratschky V, Brenner C, Zipfel PF, Brade V, et al. Identification and functional characterization of complement regulator-acquiring surface protein-1 of the Lyme disease spirochete Borrelia afzelii and Borrelia garinii. Infect. Immun. 2005;73:2351-2359
60. Haupt K, Kraiczy P, Wallich R, Brade V, Skerka C, Zipfel PF. Binding of human factor H-related protein 1 to serum-resistant Borrelia burgdorferi is mediated by Borrelial complement regulator-acquiring surface proteins. J. Infect. Dis. 2007;196:59-61.
61. Kraiczy P, Rossman E, Brade V, Simon MM, Skerka C, Zipfel PF, et al. Bidning of human complement regulators FHL-1 and factor H to CRASP-1 orthologs of Borrelia burgdorferi. Wien. Klin. Wochenschr. 2006;118:669-676
62. Hanson MS, Cassat DR, Quo BP, Patel NK, McCarthy MP, Dorward DW, et al. Active and passive immunity against Borrelia burgdorferi decorin binding protein A (DbpA) protects against infection. Infect. Immun. 1998;6:2143-2153
63. Leuba-Garcia S, Martinez R, Gem L. Expression of outer surface proteins A and C of Borrelia afzelii in Ixodes ricinus ticks and in the skin of mice. Zentbl. Bakteriol. 1998;287:475-484
64. Schwan TG, Piesman J. Temporal changes in outer surface proteins A and C of the Lyme disease-associated spirochete, Borrelia burgdorferi, during the chain of infection in ticks and mice. J. Clin. Microbiol. 2000;38:382-388
65. Heikkila T, Seppala I, Saxen H, Panelius J, Yrjänäinen H, Lahdenne P. Species specific serodiagnosis of Lyme arthritis and Neuroborreliosis due to Borrelia burgdorferi stricto, B. afzelii, B. gorinii by using Decorin binding protein A. J. Clin. Microbiol. 2002;40:453-460
66. Salazar CA, Rothemich M, Drouin EE, Glickstein L, Steere AC. Human Lyme arthritis and the immunoglobulin G antibody response to the 37-kilodalton arthritis-related protein of Borrelia burgdorferi. Infect. Immun. 2005;73:2951-2957
67. Schmid GP. Epidemiology and clinical similarities of human spirochetal diseases. Rev. Infect. Dis. 1989;2:51460-51469
68. Guyard C, Chester ME, Raffel SJ, Schrumpf ME, Policastro PF, Porcella SF, et al. Relapsing fever spirochetes contain chromosomal genes with unique direct tandemly repeated sequences. Infect. Immun. 2005;73:3035-3037
69. Homer MJ, Lodes MJ, Reynolds LD, Zhang Y, Douglass JF, McNeill PD, et al. Identification and characterization of putative secreted antigens from Babesia microti. J. Clin. Microbiol. 2003;41:723-729
70. Brown WC, McGuire TC, Zhu D, Lewin HA, Sosnow J, Palmer GH. Highly conserved regions of the immunodominant major surface protein 2 of the genogroup II Ehrlichial pathogen Anaplasma marginale are rich in naturally derived CD4+ T lymphocyte epitopes that elicit strong responses. J. Immunol. 2001;166:1114-1124 (Pubitemid 32060270)
71. Gilmore RD, Bellville TM, Sviat SL, France M. The Bartonella vinsonii subsp. arupensis immunodominant surface antigen BrpA gene, encoding a 382-kilodalton protein composed of repetitive sequence, is a member of a multigene family conserved among Bartonella species. Infect. Immun. 2005;73:3128-3136
72. Werner JA, Feng S, Kasten RW, Hodzec E, Chomel BB, Barthold SW. Cloning, characterization and expression of Bartonella henselaeP26. Clin. Vaccine. Immunol. 2006;13:830-836
73. Rawlins ML, Gerstner C, Hill HR, Litwin CM. Evaluation of a western blot method for detection of Yersinia antibodies: evidence of serological cross-reactivity between Yersinia outer membrane proteins and Borrelia burgdorferi. Clin. Diag. Lab. Immunol. 2005;12:1269-1274
74. Bruckbauer HR, Preac-Mursic V, Fuchs R, Wilske B. Cross-reactive proteins of Borrelia burgdorferi. Eur. J. Clin. Microbiol. Infect. Dis. 1992;11:224-232
75. Sobieszczanska B, Prozondo-Mordanska A. Cross-reactivity between Borrelia burgdorferi and arthrogenic bacteria in sera from patients with reactive arthritis. Rocz. Akad. Med. Bialmyst. 1996;41:90-95.
76. Grogan JL, Kramer A, Nogai A, Dong L, Ohde M, Schneider-Mergener J, et al. Cross-reactivity of myelin basic protein-specific T-cells with multiple microbial peptides: Experimental autoimmune encephalomyelitis induction in TCR transgenic mice. J. Immunol. 1999;163:3764-3770 (Pubitemid 29450900)
77. Vojdani A, Campbell AW, Anyanwu E, Kashanian A, Bock K, Vojdani E. Antibodies to neuron-specific antigens in children with autism: possible cross-reaction with encephalitogenic proteins from milk. Chlamydia pneumoniae and Streptococcus group A. J. Neuroimmunol. 2002;129:168-177
78. Vojdani A, Vojdani E, Cooper EL. Antibodies to myelin basic protein, myelin oligodendrocytes peptides, α-β-crystallin, lymphocyte activation and cytokine production in patients with multiple sclerosis. J. Internal Med. 2003;254:363-374 (Pubitemid 37211260)
79. Greunewald R, Ropper AH, Lior H. Serologic evidence of Campylobacter jejuni coli enteritis in patients with Guillain-Barre syndrome. Arch. Neurol. 1991;48:1080-1082
80. Benvenga S, Guarneri F, Vaccaro M, Santarpia L, Trimarchi F. Homologies between proteins of Borrelia burgdorferi and thyroid autoantigens. Thyroid 2004;14:964-966 (Pubitemid 39612916)
81. Ghosh S, Seward R, Costello CE, Stollar BD, Huber BT. Autoantibodies from synovial lesions in chronic, antibiotic treatment-resistant Lyme arthritis bind cytokeratin-10. J. Immunol. 2006;177:2486-2494 (Pubitemid 44201008)
82. Hu LT, Perides G, Noring R, Klempner MS. Binding of human plasminogen to Borrelia burgdorferi. Infect. Immun 1995;63:3491-3496
83. Ahrens D, Koch AE, Pope RM, Stein.Picarella M, Niedbala MJ. Expression of matrix metalloproteinase 9 (96-kd gelatinase B) in human rheumatoid arthritis. Arthritis Rheum. 1996;39:1576-1587 (Pubitemid 26314993)
84. Behera AK, Hilderbrand E, Scagliotti J, Steere AC, Hu LT. Induction of host matrix metalloproteinases by Borrelia burgdorferi differs in human and murine Lyme arthritis. Infect. Immun. 2005;73:126-134
85. Halperin JJ, Volkman DJ, Wu P. Central nervous system abnormalities in Lyme neuroborreliosis. Neurology 1991;41:1571.
86. Schmutzhard E, Pohl P, Stanek P. Borrelia burgdorferi antibodies in patients with relapsing-remitting form and chronic progressive form of multiple sclerosis. J. Neurol. Neurosur. Psychiatry 1988;51:1215.
87. Garcia-Monco JC, Villar BF, Alen JC, Benach JL. Borrelia burgdorferi in the central nervous system: experimental and clinical evidence for early invasion. J. Infect. Dis. 1990;161:1187-1193
88. Kim KS. Pathogenesis of bacterial meningitis from bacteraemia to neuronal injury. Nat. Rev. Neurosci. 2004;4:376-385
89. Coleman JL, Benach JL. The urokinase receptor can be induced by Borrelia burgdorferi through receptor of the innate immune system. Infect. Immun. 2003;71:5556-5564
90. Grab DJ, Perides G, Dumler JS, Kim KJ, Park J, Kim YV, et al. Borrelia burgdorferi, host-derived proteases and the blood-brain barrier. Infect. Immun. 2005;73:1014-1022
91. Alarcon-Chaidez F, Ryan R, Wikel S, Dardick K, Lawler C, Foppa IM, et al. Confirmation of tick bite by detection of antibody to Ixodes calreticulin salivary protein. Clin. Vaccine Immunol. 2006;13:1217-1222
92. Garg R, Juncadella IJ, Ramamoorthi N, Ananthnarayanan SK, Thomas V, Rincon M, et al. Cutting edge: CD4 is the receptor for the tick saliva immunosuppressor, Salp15. J. Immunol. 2006;177:6579-6583
93. Alaedini A, Latov N. Antibodies against OspA epitopes of Borrelia burgdorferi cross-react with neural tissue. J. Neuroimmunol. 2005;159:192-195 (Pubitemid 40126192)
94. Riberiro JMC, Alarcon-chaidez F, Francischetti IMB, Mans B, Mather TN, Valenzuela JG, et al. An annotated catalog of salivary gland transcripts from Ixodes scapularis ticks. Insect Biochem. Mol. Biol. 2006;36:111-129
95. Hsu HC, Wu Y, Yang P, Wu Q, Job G, Chen J, et al. Overexpression of activation-induced cytidine deaminase in B cells is associated with production of highly pathogenic autoantibodies. J. Immunol. 2007;178:5357-5365 (Pubitemid 46595322)
96. Yurasov S, Wardemann H, Hammersen J, Tsuiji M, Meffre E, Pascual V, et al. Defective B cell tolerance checkpoints in systemic lupus erythematosus. J. Exp. Med. 2005;201:703-711
97. Notkins AL. New predictors of disease. Scientific American 2007;296:72-79