Borrelia miyamotoi infection leads to cross-reactive antibodies to the C6 peptide in mice and men

Joris Koetsveld1,,'Correspondence information about the author Joris Koetsveld
Alexander E. Platonov2
Konstantin Kuleshov2
Alex Wagemakers1
Dieuwertje Hoornstra1
Wim Ang3
Sandor Szekeres4
Gilian L.A. van Duijvendijk5
Erol Fikrig6
Monica E. Embers7
Hein Sprong4
Joppe W. Hovius1,∗∗,'Correspondence information about the author Joppe W. Hovius



Borrelia miyamotoi is a relapsing fever Borrelia, transmitted by hard (Ixodes) ticks, which are also the main vector for Borrelia burgdorferi. A widely used test for serodiagnosis of Lyme borreliosis is an EIA based on the C6 peptide of the B. burgdorferi sl VlsE protein. We set out to study C6 reactivity upon infection with B. miyamotoiin a large well-characterized set of Borrelia miyamotoi disease (BMD) patient sera and in experimental murine infection.


We performed in-silico analyses, comparing the C6-peptide to immunodominant B. miyamotoi variable large proteins (Vlps). Next, we determined C6 reactivity in sera from mice infected with B. miyamotoi and in a unique longitudinal set of 191 sera from 46 BMD patients.


In-silico analyses revealed similarity of the C6-peptide to domains within B. miyamotoi Vlps. Cross-reactivity against the C6-peptide was confirmed in 21/24 mice experimentally infected with B. miyamotoi.Moreover, 35/46 BMD patients had a C6 EIA Lyme-index higher than 1.1 (positive). Interestingly, 27/37 patients with a C6 EIA Lyme-index higher than 0.9 (equivocal) were negative when tested for specific B. burgdorferi sl antibodies using a commercially available immunoblot.


We show that infection with B. miyamotoi leads to cross-reactive antibodies to the C6-peptide. Since BMD and Lyme borreliosis are found in the same geographical locations, caution should be used when relying solely on C6-reactivity testing. We propose that a positive C6 EIA with negative immunoblot, especially in patients with fever several weeks after a tick bite, warrants further testing for B. miyamotoi.



For a great read on cross -reactivity in testing:  Written by Dr. Jaller

The article makes some excellent points:

  • As of 2014 Labcorp no longer allows physicians to order Western Blots for Lyme disease. The only test available is the ELISA with reflex to Western Blot if positive.
  • They have also taken away the C6 peptide.  The results are presented as only negative if less than 0.91
  • Some ID doctors are inappropriately applying the HIV testing paradigm in the case of Lyme testing
  • The IDSA claims, without reference, there’s a lot of false positive Lyme Western Blots because of cross reactivity
  • The test was developed based on a meeting 20 years ago for surveillance (an epidemiology or research tool) not for diagnosis
  • The long arm of the IDSA has managed to promote its agenda by manipulating the CDC and now Labcorp
  • CDC’s Dr. Beard’s s comment to the author was an admission that politics have trumped reason, logic and science when he stated about the flawed testing, “Well, that’s the party line.”
The testing stronghold dilemma continues unabated in the topsy-turvy world of Lymeland.



“I am Barbara Johnson. I am a biochemist by training and I am speaking today on behalf of the Centers for Disease Control and Prevention concerning serodiagnosis of Lyme disease. Specifically, my statement is in support of (the) IDSA recommendation in the guidelines to use two-tiered serology (an ELISA screening test followed by Western Blots if ELISA positive) to support the diagnosis of Lyme disease in patients who have manifestations other than acute erythema migrans.  – IDSA Lyme Disease Review Panel Hearing, July 30, 2009

For more dirty deeds done dirt cheap: ConflictReport


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