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Updated: Jun 26, 2026

Measuring the 50% Haemolytic Complement (CH50) Activity of Serum
Published on: March 29, 2010
Complement split products c3a and c4a in chronic lyme disease
R B Stricker1, V R Savely, N C Motanya
1International Lyme and Associated Diseases Society, Bethesda, MD, USA. rstricker@usmamed.com
Insights
Complement split product C4a is elevated in chronic Lyme disease patients with musculoskeletal symptoms. C4a levels correlate with treatment response, indicating its value as an immunologic marker for persistent Lyme disease.
Area of Science:
- Immunology
- Infectious Diseases
- Rheumatology
Background:
- Complement split products C3a and C4a are elevated in acute Lyme disease.
- Investigating these markers in chronic Lyme disease is crucial for understanding disease progression and treatment efficacy.
Purpose of the Study:
- To compare C3a and C4a levels in chronic Lyme disease patients with healthy controls, SLE, and AIDS patients.
- To determine the correlation of these markers with disease symptoms, treatment response, and diagnostic imaging (SPECT).
Main Methods:
- Radioimmunoassay was used to measure C3a and C4a levels.
- Study included 445 chronic Lyme disease patients, 29 healthy controls, 11 SLE patients, and 6 AIDS patients.
- Lyme patients were categorized by predominant musculoskeletal or neurologic symptoms.
Main Results:
- Chronic Lyme disease patients with musculoskeletal symptoms showed normal C3a and elevated C4a levels.
- Elevated C4a levels in chronic Lyme disease correlated with lack of response to antibiotic therapy.
- C4a levels decreased with successful antibiotic treatment, unlike persistently elevated levels in AIDS patients.
Conclusions:
- C4a is a valuable immunologic marker for persistent Lyme disease, particularly in patients with musculoskeletal symptoms.
- C4a levels and their changes during treatment can help assess therapeutic response in chronic Lyme disease.
- The distinct C3a and C4a profiles differentiate chronic Lyme disease from acute Lyme disease and other autoimmune/infectious conditions.
Abstract:
Complement split products C3a and C4a are reportedly elevated in patients with acute Lyme disease. We have now examined these immunologic markers in patients with chronic Lyme disease compared to appropriate disease controls. The study population consisted of 29 healthy controls, 445 patients with chronic Lyme disease, 11 patients with systemic lupus erythematosus (SLE) and six patients with AIDS. The Lyme disease patients were divided according to predominant musculoskeletal symptoms (324 patients) or predominant neurologic symptoms (121 patients). C3a and C4a levels were measured by radioimmunoassay. All patients with chronic Lyme disease and AIDS had normal C3a levels compared to controls, whereas patients with SLE had significantly increased levels of this marker. Patients with predominant musculoskeletal symptoms of Lyme disease and AIDS patients had significantly increased levels of C4a compared to either controls, patients with predominant neurologic symptoms of Lyme disease or SLE patients. Response to antibiotic therapy in chronic Lyme disease was associated with a significant decrease in the C4a level, whereas lack of response was associated with a significant increase in this marker. In contrast, AIDS patients had persistently increased C4a levels despite antiretroviral therapy. Lyme patients with positive single-photon emission computed tomographic (SPECT) scans had significantly lower C4a levels compared to Lyme patients with normal SPECT scan results. Patients with predominant musculoskeletal symptoms of Lyme disease have normal C3a and increased C4a levels. This pattern differs from the increase in both markers seen in acute Lyme disease, and C4a changes correlate with the response to therapy in chronic Lyme disease. C4a appears to be a valuable immunologic marker in patients with persistent symptoms of Lyme disease.
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