Expression of C-Reactive Protein and Serum Amyloid A in Early to Late Manifestations of Lyme Disease

Clin Infect Dis. 2016 Dec 1;63(11):1399-1404. doi: 10.1093/cid/ciw599. Epub 2016 Sep 1.


Background: Infection with Borrelia burgdorferi, the causative agent of Lyme disease, triggers host immune responses that affect the clinical outcome and are a source of biomarkers with diagnostic utility. Although adaptive immunity to B. burgdorferi has been extensively characterized, considerably less information is available about the development of innate acute-phase responses in Lyme disease. Our aim in this study was to evaluate the expression of C-reactive protein (CRP) and serum amyloid A (SAA), the prototype acute-phase response proteins, in the context of the varying manifestations associated with Lyme borreliosis.

Methods: Circulating concentrations of CRP and SAA in patients with a range of early to late objective manifestations of Lyme disease and in individuals with post-treatment Lyme disease syndrome were compared with those in healthy control groups.

Results: CRP and SAA levels were significantly elevated in early localized and early disseminated Lyme disease but not in the later stages of active infection. Levels of CRP, but not SAA, were also found to be significantly increased in patients with antibiotic-refractory Lyme arthritis and in those with post-treatment Lyme disease syndrome.

Conclusions: These findings indicate that circulating CRP and SAA levels are highest when the concentration of spirochetes is greatest in skin and/or blood and that levels decline after the dissemination of the organism to extracutaneous sites in subsequent stages of infection. The data also suggest that antibiotic-refractory Lyme arthritis and post-treatment Lyme disease syndrome are associated with elevated CRP responses that are driven by inflammatory mechanisms distinct from those in active infection.

Keywords: Borrelia burgdorferi; Lyme disease; acute-phase response; inflammation; post-treatment Lyme disease syndrome.

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / therapeutic use
  • Antibodies, Bacterial / blood
  • Biomarkers / blood
  • Borrelia burgdorferi / immunology
  • Borrelia burgdorferi / isolation & purification
  • C-Reactive Protein / analysis*
  • C-Reactive Protein / genetics
  • Female
  • Humans
  • Immunity, Innate
  • Inflammation
  • Lyme Disease / blood*
  • Lyme Disease / drug therapy
  • Lyme Disease / immunology
  • Lyme Disease / microbiology
  • Male
  • Middle Aged
  • Serum Amyloid A Protein / analysis*
  • Serum Amyloid A Protein / genetics


  • Anti-Bacterial Agents
  • Antibodies, Bacterial
  • Biomarkers
  • Serum Amyloid A Protein
  • C-Reactive Protein