Can a C4a (Complement Component 4a) test help with Lyme disease?

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Last updated: February 15, 2025View editorial policy

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From the Guidelines

No, a C4a (Complement Component 4a) test is not recommended to help with Lyme disease diagnosis.

Diagnostic Tests for Lyme Disease

The recommended laboratory test in the United States is a 2-tiered serologic analysis consisting of an enzyme-linked immunoassay or immunofluorescence assay, followed by reflexive immunoblotting 1.

  • The sensitivity of 2-tiered testing is low (30%–40%) during early infection, but it increases to 70%–100% for disseminated Lyme disease.
  • The specificity is high (>95%) during all stages of disease.

Limitations of Alternative Tests

There is no mention of C4a tests in the provided guidelines, and the use of other diagnostic tests for Lyme disease is limited 1.

  • The guidelines emphasize the importance of using FDA-cleared diagnostic tests and understanding the hazards of alternative laboratory tests 1.

Clinical Diagnosis

Patients with a lesion consistent with erythema migrans and a history of exposure to Lyme-endemic areas can be diagnosed without laboratory testing 1.

  • However, for all other manifestations of Lyme disease, serologic analysis is necessary to confirm the diagnosis.

Future Directions

Research is ongoing to improve the diagnosis of early Lyme disease and reduce the subjectivity of second-tier Western immunoblotting 1.

  • A repository of well-characterized serum samples from patients with Lyme disease has been developed to evaluate novel diagnostic tests 1.

From the Research

C4a Test and Lyme Disease

  • The C4a test can be a useful marker in patients with Lyme disease, particularly in those with chronic Lyme disease 2.
  • Studies have shown that C4a levels are elevated in patients with acute Lyme disease, and this elevation can be used as an early marker of the disease 3.
  • In patients with chronic Lyme disease, C4a levels have been found to be increased in those with predominant musculoskeletal symptoms, and a decrease in C4a levels has been associated with response to antibiotic therapy 2.
  • The C4a test may be more useful in certain stages of Lyme disease, such as in early localized and early disseminated disease, where C-reactive protein (CRP) and serum amyloid A (SAA) levels are also elevated 4.
  • It is essential to note that the diagnosis of Lyme disease is challenging and requires a combination of clinical findings, laboratory tests, and assessment of the patient's pretest probability of infection 5.
  • Other laboratory tests, such as the complement fixation test, may also be useful in diagnosing Lyme disease, particularly in confirmed cases 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Complement split products c3a and c4a in chronic lyme disease.

Scandinavian journal of immunology, 2009

Research

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

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2016

Research

Appropriate laboratory testing in Lyme disease.

Cleveland Clinic journal of medicine, 2019

Research

Complement fixation test for the diagnosis of Lyme disease.

Journal of clinical microbiology, 1990

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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