title: Effect of Borrelia burgdorferi genotype on the sensitivity of C6 and 2-tier testing in North American patients with culture-confirmed Lyme disease.
abstract: 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.
authors: Division of Infectious Diseases, Department of Medicine, New York Medical College, Valhalla, NY 10595, USA. gary_wormser@nymc.edu
authors: Gary P
authors: GP
authors: Wormser
authors: Dionysios
authors: D
authors: Liveris
authors: Klára
authors: K
authors: Hanincová
authors: Dustin
authors: D
authors: Brisson
authors: Sara
authors: S
authors: Ludin
authors: Vincent J
authors: VJ
authors: Stracuzzi
authors: Monica E
authors: ME
authors: Embers
authors: Mario T
authors: MT
authors: Philipp
authors: Andrew
authors: A
authors: Levin
authors: Maria
authors: M
authors: Aguero-Rosenfeld
authors: Ira
authors: I
authors: Schwartz
mesh_terms: 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
chemical_list: D000907:Antibodies, Bacterial; D021903:DNA, Ribosomal Spacer; D011933:Reagent Kits, Diagnostic