From the Guidelines
Low complement C4 levels are a key indicator of Hereditary Angioedema (HAE) and should be further investigated through laboratory testing to confirm diagnosis. When a patient presents with low complement C4 levels, it is essential to consider HAE as a potential diagnosis, particularly type I or type II HAE, which are characterized by low C1INH antigenic or functional levels and decreased C4 levels 1. According to the study published in the Journal of Allergy and Clinical Immunology, measuring complement C4 levels is recommended as the best initial screening test to exclude a diagnosis of HAE 1. Some key points to consider in the diagnosis and management of low complement C4 levels include:
- Measuring complement C4 levels as the initial screening test for HAE
- Confirming diagnosis through laboratory testing, including C1INH antigenic or functional levels and C1q levels
- Considering the typical patterns of complement levels for different types of HAE and other conditions, such as acquired C1INH deficiency and ACE-I–associated angioedema
- Using an algorithm for the diagnosis of HAE, as shown in Fig E1 of the study 1 It is crucial to consult with a specialist, such as an allergist or immunologist, for proper evaluation and management of low complement C4 levels, as treatment approaches differ significantly between acquired consumption and genetic deficiency.
From the Research
Low Complement C4
- Low complement C4 levels have been associated with various autoimmune diseases, including systemic lupus erythematosus (SLE) 2, 3.
- Complement C4 plays a crucial role in the classical and lectin complement pathways, and its deficiency can lead to increased susceptibility to microbial infections and autoimmune disorders 2.
- Studies have shown that low serum complement C4 levels can be a diagnostic criterion for SLE, with a sensitivity of 80.1% and specificity of 83.2% 3.
- The prevalence of low C4 levels is higher in patients with SLE, and hypocomplementemia (low C3 and C4 levels) is a common feature of the disease 3.
Association with Autoimmune Diseases
- Low complement C4 levels have been linked to an increased risk of SLE, rheumatoid arthritis, and other autoimmune diseases 4, 5, 6.
- The presence of SLE features in patients with rheumatoid arthritis can increase the risk of mortality, with thrombocytopenia and proteinuria being individually associated with an increased mortality risk 6.
- The innate immune system, including complement C4, plays a crucial role in the pathophysiology of autoimmune diseases, and alterations in its function can contribute to disease progression 5.
Diagnostic Value
- Low serum complement C4 levels can be a useful diagnostic tool for SLE, particularly when used in combination with other immunologic criteria 3.
- The diagnostic value of low C4 levels is enhanced when used in conjunction with antinuclear antibody testing, which can help to improve the sensitivity and specificity of SLE diagnosis 3.
- Further research is needed to fully understand the diagnostic value of low complement C4 levels in various autoimmune diseases and to develop effective treatment strategies 2, 4, 5, 3, 6.