Effect of Borrelia burgdorferi genotype on the sensitivity of C6 and 2-tier testing in North American patients with culture-confirmed Lyme disease.
BACKGROUND
A potential concern with any serologic test to detect antibodies to Borrelia burgdorferi is whether the epitopes incorporated in the test provide sufficient cross-reactivity to detect infection with all of the pathogenic strains of the species. This is a particular concern for the C6 test, which is based on reactivity to a single peptide.


METHODS
C6 testing and 2-tier testing were performed on acute-phase serum samples obtained from >158 patients with erythema migrans for whom the genotype of the borrelial isolate was defined on the basis of an analysis of the 16S-23S ribosomal DNA spacer region and/or on the genetic variation of the outer surface protein C gene (ospC). The sonicated whole cell-based enzyme-linked immunosorbent assay, the immunoblots used in the 2-tier testing, and the C6 assay all used antigens from B. burgdorferi sensu stricto strain B31.


RESULTS
The sensitivity of C6 testing (69.5%) was greater than that of 2-tier testing (38.9%) (P<.001); the difference in sensitivity, however, was statistically significant only for patients infected with 2 of the 3 ribosomal spacer type-defined genotypes. The lower sensitivity of 2-tier testing was attributable to the low sensitivity of the immunoblot tests, rather than the first-tier enzyme-linked immunosorbent assay. There was also a trend for the sensitivity of 2-tier testing to vary according to the ospC genotype for the 14 genotypes represented in the study (P=.07); this relationship was not observed with C6 testing.


CONCLUSIONS
Lack of sensitivity of the C6 test because of strain diversity seems less likely to be a limitation of this serologic test, compared with 2-tier testing in North American patients with early Lyme disease.
Wormser
Gary P
GP
Division of Infectious Diseases, Department of Medicine, New York Medical College, Valhalla, NY 10595, USA. gary_wormser@nymc.edu
Liveris
Dionysios
D
Hanincová
Klára
K
Brisson
Dustin
D
Ludin
Sara
S
Stracuzzi
Vincent J
VJ
Embers
Monica E
ME
Philipp
Mario T
MT
Levin
Andrew
A
Aguero-Rosenfeld
Maria
M
Schwartz
Ira
I
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D025065:Borrelia burgdorferi / Q000235:genetics*; D021903:DNA, Ribosomal Spacer / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005838:Genotype; D006801:Humans; D008193:Lyme Disease / Q000175:diagnosis*; D051379:Mice; D008809:Mice, Inbred C3H / Q000276:immunology; D009518:New York; D011933:Reagent Kits, Diagnostic; D012680:Sensitivity and Specificity
D000907:Antibodies, Bacterial; D021903:DNA, Ribosomal Spacer; D011933:Reagent Kits, Diagnostic