What are the levels of Complement 3 (C3) and Complement 4 (C4)?

From the Guidelines

Normal levels of Complement 3 (C3) and Complement 4 (C4) are typically considered to be within the normal range, but the exact values can vary depending on the laboratory and the individual's health status.

Key Points

• The levels of C3 and C4 can be affected by various factors, including infections, autoimmune disorders, and genetic deficiencies 1.
• Low levels of C3 and C4 can indicate consumption of complement, which can be seen in conditions such as systemic lupus erythematosus (SLE) or other autoimmune disorders 1.
• In patients with SLE, monitoring of C3 and C4 levels is recommended at baseline and during follow-up visits to assess disease activity and response to treatment 1.
• For patients with complement deficiencies, all viral vaccines can be given, and pneumococcal, Hib, and meningococcal vaccines are strongly recommended due to the predilection of complement deficient patients to acquire these bacterial infections 1.

Measurement of C3 and C4

• C3 and C4 levels can be measured using various laboratory tests, including nephelometry or radial immunodiffusion 1.
• The results of these tests should be interpreted in the context of the individual's clinical presentation and medical history.

Clinical Significance

• Low levels of C3 and C4 can indicate an increased risk of infections or autoimmune disorders, and may require further evaluation and treatment 1.
• In patients with complement deficiencies, vaccination with pneumococcal, Hib, and meningococcal vaccines is crucial to prevent infections 1.

From the Research

Complement 3 (C3) and Complement 4 (C4) Levels

The levels of Complement 3 (C3) and Complement 4 (C4) can be influenced by various factors, including age, sex, and inflammatory conditions.

• C3 and C4 are measured for clinical purposes to help define certain rheumatic and immunologically mediated renal diseases 2.
• The levels of C3 and C4 change little during life and between the sexes, except that they increase slightly and then fall after age 20 in males and at about age 45 in females 2.
• Elevated serum complement factors 3 and 4 are strong inflammatory markers of the metabolic syndrome development 3.
• High complement levels, defined as either C3 or C4 in the top quartile, are associated with an increased incidence of atrial fibrillation 4.
• Serum C4 levels are effective indicators of disease activity in osteoarthritis, particularly in terms of joint involvement and CRP levels 5.

Genetic Influence on C3 and C4 Levels

Genetic components can influence the levels of complement C3 and C4.

• A genome-wide association study identified two SNPs, rs3753394 in CFH gene and rs3745567 in C3 gene, that are significantly associated with serum C3 levels 6.
• For C4, one large genomic region on chromosome 6p21.3 is significantly associated with serum C4 levels, including SNPs located in the MHC class I and II areas 6.
• HBsAg-positive subjects have significantly lower C3 and C4 protein concentrations compared with HBsAg-negative subjects 6.

Clinical Relevance of C3 and C4 Levels

The measurement of C3 and C4 levels can be useful in clinical practice.

• Interpreting the measured blood levels of these two components requires consideration of the intensity of the inflammatory drive, the timing of the suspected clinical process, the production of complement-consuming immune complexes, and the possible existence of benign circumstances 2.
• The distribution parameters of C3 and C4 levels can be used to assign a centile corresponding to an individual's measurement, thus simplifying interpretation 2.