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

Abstract

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 antibioticrefractory 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.

Post-treatment Lyme Disease as a Model for Persistent Symptoms in Lyme Disease

“…This is important in order to rule out other symptom causes such as severe anemia, liver, kidney or other metabolic conditions such as diabetes, or other inflammatory or neoplastic conditions. Mild elevations in C-reactive protein have been reported in PTLD (106), however moderate to severe elevations in the erythrocyte sedimentation rate or C-reactive protein are distinctly unusual and should prompt evaluation of another infectious, neoplastic, or autoimmune condition, such as polymyalgia rheumatica.…”

“…Investigation into the role of an ongoing immune response in the symptomatology of patients with persistent symptoms is in its earliest stages. A handful of studies have suggested that inflammatory markers such as C-reactive protein, as well as immune mediators such as CCL19 and IL-23, remain elevated for months after completion of antibiotic therapy among patients with persistent symptoms (47,48,106). Anti-neural antibody reactivity is higher in those with persistent symptoms, even among those who are seronegative, compared to those who returned to health after treatment for Lyme disease (149).…”

Identifying Vancomycin as an Effective Antibiotic for Killing Borrelia burgdorferi

“…Unfortunately, there is currently no good test, genetic or otherwise, to identify patients at higher risk for developing PTLDS a priori who may benefit from more aggressive therapy with intravenous antibiotics. There are several markers reported that may be related to PTLDS, such as increased immune response to VlsE membrane-proximal epitopes in PTLDS patients (39), innate acute C-reactive protein (40), T-cell chemokine CCL19 (41), and greater frequency of the TLR1-1805GG polymorphism (42). It seems possible that a combination of several markers may provide a basis for identifying high-risk patients for PTLDS.…”

Reply to Naktin

“…To the Editor-We thank Naktin for his letter [1] regarding our recently published study in Clinical Infectious Diseases [2] in which we examined the expression of acute phase response proteins in patients with various manifestations of Lyme disease. Naktin expressed concern over the extrapolation that was made regarding the level of anti-Borrelia burgdorferi antibody based on the optical density (OD) signal measured in the enzyme-linked immunosorbent assay.…”