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Occurrence of Antibodies to Borrelia burgdorferi in Patients with Nonspirochetal Subacute Bacterial Endocarditis

Alan T. Kaell, MD; Patricia R. Redecha, BS; Keith B. Elkon, MD; Marc G. Golightly, PhD; Paul E. Schulman, MD; Raymond J. Dattwyler, MD; Diana L. Kaell, BS; Robert D. Inman, MD; Charles L. Christian, MD; and David J. Volkman, PhD, MD
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From the State University of New York at Stony Brook, Stony Brook, and Cornell University Medical Center, New York, New York; Toronto Western Hospital, Toronto, Ontario, Canada. Acknowledgments: The authors thank Dr. Shelly Cohen for statistical assistance, Marie DeHart for secretarial assistance, and Josephine Schultz for technical assistance. Grant Support: In part by grant P01 AI2972301 from the National Institutes of Health.

Copyright 2004 by the American College of Physicians

Ann Intern Med. 1993;119(11):1079-1083. doi:10.7326/0003-4819-119-11-199312010-00004
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Objective: To determine the prevalence and specificity of antibodies to Borrelia burgdorferi in patients with nonspirochetal subacute bacterial endocarditis and assess whether increased levels of antibodies to B. burgdorferi were attributable to rheumatoid factor.

Design: Retrospective casecontrol study.

Setting: Urban referral center in an area devoid of infected ticks as a source of endocarditis sera.

Patients: Sera from 30 consecutive patients with culture-proven subacute endocarditis between 1979 and 1981 were compared with 30 control sera collected between 1989 and 1990. In addition, sera from 20 consecutive patients with rheumatoid arthritis who were positive for rheumatoid factor were collected between 1991 and 1992. Sera were compared with a convenience sample from 15 patients who met the criteria for Lyme disease.

Measurements: Antibodies to B. burgdorferi were assessed by enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis. IgM rheumatoid factor was quantified using solid-phase radioimmunoassay or latex agglutination techniques.

Results: Thirteen of 30 patients with endocarditis (43%) compared with 3 of 30 normal controls (10%) had increased levels of antibodies to B. burgdorferi (P < 0.01). Of these 13 patients, only 1 had an immunoblot consistent with previous infection. The others had nonspecific immunoblots: 5 showed isolated 60-kd reactivity; 1 patient had isolated 41-kd reactivity; and 6 had no bands of reactivity. Immunoblots of the 3 controls with increased antibodies showed only isolated 41-kd reactivity. Thus, the specificity of the B. burgdorferi antibody test in patients with endocarditis was only 60% (95% CI, 42% to 78%), compared with 90% (CI, 79% to 100%) in controls. No correlation was noted between IgM rheumatoid factor and antibodies to B. burgdorferi in patients with endocarditis (r = 0.2; P > 0.2). Only 1 of 20 patients with rheumatoid arthritis with out known bacterial infections had antibodies to B. burgdorferi.

Conclusions: Although a positive ELISA test for B. burgdorferi may be a true positive, a positive serologic test alone does not ensure that the clinical problem is due to Lyme borreliosis. Cross-reactive antibodies to shared epitopes between B. burgdorferi and the endocarditis organism may account for the high false-positive results.


Grahic Jump Location
Figure 1.
Immunoblot analysis of sera from 23 of 30 patients with nonspirochetal bacterial endocarditis who reside in nonendemic areas for Lyme disease.BorreliaB. burgdorferiB. burgdorferiB. burgdorferi

Sera was blotted against solubilized antigen ( strain 31) and was probed with anti-human IgG, -chain-specific goat antibody conjugated to alkaline phosphatase. A positive control serum sample in lane 1 shows an expanded humoral response in a patient with newly diagnosed chronic Lyme disease. Thirteen of the sera from patients with carditis yielded positive ELISA results for (lanes 3, 4, 6, 7, 8, 12, 13, 16, 17, 18, 19, 22, and 23). Immunoblots from the remaining 17 patients with endocarditis, who had nonreactive ELISA results for , were indistinguishable from negative control results (data shown for nine patients).

Grahic Jump Location
Grahic Jump Location
Figure 2.
Relation between IgM rheumatoid factor and B. burgdorferi antibody levels in 13 patients with endocarditis.BorreliaB. burgdorferiP

The values are shown for quantitative IgM rheumatoid factor and anti- ELISA indices that represent the ratio of the sample values to the negative cut-off value. No significant correlation was noted between IgM rheumatoid factor and antibody levels (Lyme antibody index) using linear regression analysis (R = 0.2; > 0.2).

Grahic Jump Location
Grahic Jump Location
Figure 3.
Relation between IgM rheumatoid factor and B. burgdorferi antibody levels.Left.Right.Borrelia

In 15 patients from Suffolk County with seropositive Lyme disease. In 20 patients with documented rheumatoid arthritis. Rheumatoid factor and antibody levels are shown as in Figure 2.

Grahic Jump Location




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