From the Guidelines
An isolated elevated complement C3 level can be caused by various underlying conditions, including infections, autoimmune diseases, and malignancies, as suggested by the most recent guideline evidence 1. When evaluating an isolated elevated C3 level, it is essential to consider the clinical context and potential causes. According to the 2023 commentary on the kdigo clinical practice guideline for the management of glomerular diseases 1, a pattern of MPGN with dominance of polyclonal immunoglobulin and complement is most often due to infectious or autoimmune disease. Some potential causes of an isolated elevated C3 level include:
- Infections, such as hepatitis B and C, chronic microbial infections, and bacterial or parasitic diseases 1
- Autoimmune disorders, including mixed cryoglobulinemia, systemic lupus erythematosus (SLE), Sjögren syndrome, and rheumatoid arthritis 1
- Malignancies, such as leukemia, lymphoma, and carcinoma 1
- Metabolic conditions, like diabetes mellitus and obesity, which can lead to increased C3 production by adipose tissue
- Genetic factors or rare complement regulatory disorders, which may result in persistently elevated C3 It is crucial to interpret the elevated C3 level in the context of the patient's clinical presentation and consider these potential causes, as C3 elevation alone is rarely diagnostic of a specific condition but rather reflects an underlying inflammatory or immune process. Therefore, a thorough evaluation for an underlying cause of antigenemia that can trigger the classical pathway, as outlined in the guideline evidence 1, is necessary to determine the cause of the isolated elevated C3 level.
From the Research
Potential Causes of Isolated Elevated Complement C3 Level
- Elevated serum complement C3 levels have been associated with prehypertension in an adult population, suggesting a potential link between C3 and cardiovascular health 2.
- Complement C3 plays a central role in the innate immune system, and its activation can be involved in various diseases, including autoimmune disorders and infections 3.
- However, the provided studies do not directly address the causes of isolated elevated complement C3 levels.
- It is worth noting that complement C3 levels can be influenced by various factors, including genetic polymorphisms, and can have different biological and clinical consequences 4.
- In some cases, elevated C3 levels may be related to inflammation or immune responses, but more research is needed to fully understand the underlying mechanisms 5, 2.