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Lyme Disease Serology 

  • Author: Bishnu Prasad Devkota, MD, MHI, FRCS(Edin), FRCS(Glasg), FACP; Chief Editor: Eric B Staros, MD  more...
Updated: Jan 15, 2014

Reference Range

Because of the significant false positivity associated with test results, even among healthy populations from nonendemic regions, serologic testing for Lyme disease should only be performed if the clinician estimates the chance is at least 20% chance that the patient has active Lyme disease.

Normal levels vary depending on the laboratory assay performed, as follows[1] :

  • Enzyme-linked immunosorbent assay (ELISA): Less than 1:8
  • Western blot: Nonreactive

See Lyme Disease and 4 Emerging Tick-Borne Illnesses, a Critical Images slideshow, to help identify and treat several tick-borne conditions.




Positive results can be found with the following:

  • Infection with Borrelia burgdorferi
  • Other rickettsial diseases
  • Asymptomatic individuals living in endemic areas
  • Immunization with recombinant outer-surface protein A (OspA) Lyme disease vaccine
  • Tick-borne relapsing fever ( Borrelia hermsii)

If results are positive, a Western blot test with multiple bands of identity should also be performed.[2, 3] Assays for anti– B burgdorferi should be used for supporting a clinical diagnosis of Lyme disease; they should not be used to screen asymptomatic individuals. The preferred term for the first step is “initial,” and the second step, Western blot, is termed “supplemental”; using the term “confirmatory” for the second result is discouraged because of suboptimal specificity.[3]


The following values are used after antibiotic therapy or during the first few weeks of disease[4] :

  • < 1.00 = negative
  • 1.19 = equivocal
  • >1.19 = positive

The US Centers for Disease Control and Prevention (CDC) recommendations are that Western blot should be used to confirm equivocal and positive results before the results are reported. Other tick-borne diseases such as ehrlichiosis or babesiosis should be considered if test results are negative.


Collection and Panels

See the list below:

  • Specimen: Blood
  • Container: Tiger-top tube (SST)

To comply with Occupational Safety and Health Administration (OSHA) safety standards, all samples must be sent in a sealed, leak-proof container marked with a biohazard sticker.



Many active or recent infections do not show detectable antibody to B burgdorferi in a single specimen. Approximately 2-4 weeks must elapse before antibodies to B burgdorferi develop; alternatively, anti– B burgdorferi may diminish or may never develop if in the presence of antibacterial treatment. Making a definite temporal association between detectable anti– B burgdorferi and the disease is impossible, owing to the fact that these antibodies do not indicate any time frame of actual infection with B burgdorferi or any actual presence of active Lyme disease.[3]

After an active infection, anti– B burgdorferi can be detected on serologic assays for many years. Thus, a positive result may be the true evidence of a prior infection with B burgdorferi and not at all related to the current disease process. Anti– B burgdorferi assays commonly yield false-positive results because of cross-reactive antibodies associated with autoimmune diseases or with spirochetal rickettsial, ehrlichial, or bacterial (eg, Helicobacter pylori) infections.[3] Also available is a polymerase chain reaction (PCR) assay that detects B burgdorferi DNA.[2]


B burgdorferi can be grown in the laboratory, but cultures generally are not performed because the results are rarely positive. Diagnosis is typically made serologically. The usual method is by detecting immunoglobulin M antibody or an elevated titer of immunoglobulin G antibody on an ELISA or with indirect immunofluorescence testing.[5]

The US Food and Drug Administration (FDA) has warned of the potential for misdiagnosis of Lyme disease. Results for assays commonly marketed for detecting antibody to B burgdorferi are subject to misinterpretation, and medical practitioners should understand that the tests have limitations. A positive result is not definitive for current active infection with B burgdorferi, and a negative result can be found in a patient with active Lyme disease.[3, 6]

Serologic testing is recommended only when at least a 20% chance exists, in the clinician's estimation, that the patient has active Lyme disease. False positivity exists even among healthy populations from nonendemic regions. To assess the pretest likelihood of active disease, both epidemiologic and clinical factors regarding the patient must be taken into consideration. This assessment can be reassuring to patients at low risk of B burgdorferi infection who are seeking Lyme testing for symptoms of a more nonspecific nature.[2]


Testing is indicated for clinically suspected cases of Lyme disease; it is not necessary if the patient has a tick bite and erythema migrans.


Diagnosis of Lyme disease is made based on a combination clinical manifestations and available testing. No test is 100% sensitive or specific for Lyme disease.[2] If the test is performed before an adequate antibody response develops, results may be false negative. In this case, repeat testing in 2-4 weeks is recommended.

The immunoglobulin M antibody response peaks 3-6 weeks after infection and thus may not be detected during the first 2 weeks of infection.[7] Most patients have a positive result if a serum sample is obtained 2 weeks after the initial sample; however, immediate initial antibiotic treatment of a seronegative patient can prevent seroconversion. Immunoglobulin G cannot be detected until after 4-6 weeks of infection. The immunoglobulin G response can sometimes continue to develop over several months and typically lasts for years. Other spirochetal disease (syphilis), autoimmune disease, or other infections such as HIV, Epstein-Barr virus, and Helicobacter pylori may cause false-positive results.[3, 4, 8, 9]

Current CDC recommendations for interpretation of Western blot define a positive immunoglobulin G immunoblot as 2 or more of the following 3 bands[10, 11] :

  • 24 kd (OspC)
  • 39 kd (BmpA)
  • 41 kd (Fla)

A positive immunoglobulin G immunoblot assay is defined as 5 of the following 10 bands[12, 13] :

  • 18 kd
  • 21 kd (OspC)
  • 28 kd
  • 30 kd
  • 39 kd (BmpA)
  • 41 kd (Fla)
  • 45 kd
  • 58 kd
  • 66 kd
  • 93 kd
Contributor Information and Disclosures

Bishnu Prasad Devkota, MD, MHI, FRCS(Edin), FRCS(Glasg), FACP Associate Professor of Medicine, St Louis University School of Medicine

Bishnu Prasad Devkota, MD, MHI, FRCS(Edin), FRCS(Glasg), FACP is a member of the following medical societies: American College of Physicians, American Medical Informatics Association, Royal College of Physicians and Surgeons of Glasgow, Royal College of Surgeons of Edinburgh, Healthcare Information and Management Systems Society

Disclosure: Nothing to disclose.

Chief Editor

Eric B Staros, MD Associate Professor of Pathology, St Louis University School of Medicine; Director of Clinical Laboratories, Director of Cytopathology, Department of Pathology, St Louis University Hospital

Eric B Staros, MD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology

Disclosure: Nothing to disclose.

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  2. Bunikis J, Barbour AG. Laboratory testing for suspected Lyme disease. Med Clin North Am. 2002 Mar. 86(2):311-40. [Medline].

  3. FDA. Public Health Advisory: Assays for Antibodies to Borrelia burgdorferi; Limitations, Use, and Interpretation for Supporting a Clinical Diagnosis of Lyme Disease. 2007. Available at Accessed: April 24, 2012.

  4. Williamson MA, Snyder LM, Wallach JB. Wallach's interpretation of diagnostic tests. 9th ed. Philadelphia, Pa: Wolters Kluwer/Lippincott Williams & Wilkins Health; 2011.

  5. Levinson W. Spirochetes. Review of Medical Microbiology and Immunology. 11th ed. New York, NY: McGraw Hill; 2010.

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  8. Schwan TG, Rosa PA. Borrelia. 6th ed. Washington DC: American Society for Microbiology; 1995.

  9. Magnarelli LA, Miller JN, Anderson JF, Riviere GR. Cross-reactivity of nonspecific treponemal antibody in serologic tests for Lyme disease. J Clin Microbiol. 1990 Jun. 28(6):1276-9. [Medline]. [Full Text].

  10. Engstrom SM, Shoop E, Johnson RC. Immunoblot interpretation criteria for serodiagnosis of early Lyme disease. J Clin Microbiol. 1995 Feb. 33(2):419-27. [Medline].

  11. Centers for Disease Control and Prevention. Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. JAMA. 1995 Sep 27. 274(12):937. [Medline].

  12. Centers for Disease Control and Prevention. Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. MMWR Morb Mortal Wkly Rep. 1995 Aug 11. 44(31):590-1. [Medline].

  13. Dressler F, Whalen JA, Reinhardt BN, Steere AC. Western blotting in the serodiagnosis of Lyme disease. J Infect Dis. 1993 Feb. 167(2):392-400. [Medline].

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