title: Detection of immune complexes is not independent of detection of antibodies in Lyme disease patients and does not confirm active infection with Borrelia burgdorferi.
abstract: The Borrelia burgdorferi-specific immune complex (IC) test, which uses polyethylene glycol (PEG) precipitation to isolate ICs from serum, has been used as a research test in the laboratory diagnosis of early Lyme disease (LD) and has been proposed as a marker of active infection. We examined whether B. burgdorferi-specific antibodies were present within PEG-precipitated ICs (PEG-ICs) in patients with LD, posttreatment Lyme disease syndrome, and controls, including individuals who received the outer surface protein A (OspA) vaccine. Using a B. burgdorferi whole-cell enzyme-linked immunosorbent assay (ELISA), we obtained positive PEG-IC results not only in patients with a history of LD, but also in individuals vaccinated with OspA vaccine. The frequency of positive PEG-IC ELISAs in OspA vaccinees was significantly higher with ELISA-reactive than with ELISA-negative unprocessed serum samples (P=0.001), demonstrating dependency between the tests. Similar results were found using samples from rhesus macaques infected with B. burgdorferi, uninfected macaques vaccinated with OspA, and controls. Therefore, testing for the presence of antibodies against B. burgdorferi in PEG-IC preparations is not more likely to reflect active infection than testing in unprocessed serum and should not be used in individuals who received the OspA vaccine.
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1888, USA. amarques@niaid.nih.gov
authors.forename: Adriana R
authors.initials: AR
authors.lastname: Marques
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hornung
authors.forename: Len
authors.initials: L
authors.lastname: Dally
authors.forename: Mario T
authors.initials: MT
authors.lastname: Philipp
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000097:blood*; D000936:Antigen-Antibody Complex / Q000032:analysis / Q000097:blood*; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D025065:Borrelia burgdorferi / Q000276:immunology*; D002353:Carrier State / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D008193:Lyme Disease / Q000175:diagnosis* / Q000276:immunology*; D008253:Macaca mulatta; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols
chemical_list: D000907:Antibodies, Bacterial; D000936:Antigen-Antibody Complex; D015415:Biomarkers; D011092:Polyethylene Glycols