Antibody Testing for Early and Late Lyme Disease

Background.Standard 2‐tiered immunoglobulin G (IgG) testing has performed well in late Lyme disease (LD), but IgM testing early in the illness has been problematic. IgG VlsE antibody testing, by itself, improves early sensitivity, but may lower specificity. We studied whether elements of the 2 approaches could be combined to produce a second‐tier IgG blot that performs well throughout the infection.

Methods.Separate serum sets from LD patients and control subjects were tested independently at 2 medical centers using whole‐cell enzyme immunoassays and IgM and IgG immunoblots, with recombinant VlsE added to the IgG blots. The results from both centers were combined, and a new second‐tier IgG algorithm was developed.

Results.With standard 2‐tiered IgM and IgG testing, 31% of patients with active erythema migrans (stage 1), 63% of those with acute neuroborreliosis or carditis (stage 2), and 100% of those with arthritis or late neurologic involvement (stage 3) had positive results. Using new IgG criteria, in which only the VlsE band was scored as a second‐tier test among patients with early LD (stage 1 or 2) and 5 of 11 IgG bands were required in those with stage 3 LD, 34% of patients with stage 1, 96% of those with stage 2, and 100% of those with stage 3 infection had positive responses. Both new and standard testing achieved 100% specificity.

Conclusions.Compared with standard IgM and IgG testing, the new IgG algorithm (with VlsE band) eliminates the need for IgM testing; it provides comparable or better sensitivity, and it maintains high specificity.

Received 27 May 2009; accepted 10 August 2009; electronically published 30 November 2009.

Reprints or correspondence: Dr. John A. Branda, Clinical Microbiology Laboratory, GRB 526, Massachusetts General Hospital, Boston, MA 02114 (branda.john@mgh.harvard.edu).

• Presented in part: 45th Annual Meeting of the Infectious Diseases Society of America, San Diego, CA, 4-7 October 2007; and 11th International Conference on Lyme Borreliosis and Other Tick‐Borne Diseases, Irvine, CA, 19-22 October 2008.

http://www.journals.uchicago.edu/doi/abs/10.1086/648674 Clinical Infectious Diseases 2010;50:000-000 © 2009 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2010/5001-00XX$15.00 DOI: 10.1086/648674 MAJOR ARTICLE

2‐Tiered Antibody Testing for Early and Late Lyme Disease Using Only an Immunoglobulin G Blot with the Addition of a VlsE Band as the Second‐Tier Test

John A. Branda,¹

Maria E. Aguero‐Rosenfeld,^3,4

Mary Jane Ferraro,^1,2

Barbara J. B. Johnson,⁵

Gary P. Wormser,⁴ and

Allen C. Steere²

Departments of ¹Pathology and ²Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Departments of ³Pathology and ⁴Medicine, Division of Infectious Diseases, New York Medical College, Valhalla, New York; ⁵Division of Vector‐Borne Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado