From the Guidelines
Elevated C3 and C4 complement proteins are typically indicative of an acute phase response to inflammation or infection, rather than a specific disease, and can be caused by various conditions such as bacterial infections, inflammatory diseases, cancer, and metabolic disorders. When considering the implications of elevated C3 and C4, it's crucial to interpret these findings in the context of the patient's overall clinical presentation and other laboratory results, as these elevations often represent a non-specific response to inflammation. Some of the conditions that can lead to elevated C3 and C4 include bacterial infections, such as sepsis and endocarditis, as well as inflammatory conditions like rheumatoid arthritis, cancer, and myocardial infarction 1. Key points to consider when evaluating elevated C3 and C4 levels include:
- The presence of underlying infections, such as hepatitis B and C, or chronic microbial infections, which can trigger the classical pathway of the complement system 1
- The possibility of autoimmune disorders, such as systemic lupus erythematosus (SLE) or rheumatoid arthritis, which can also lead to elevated complement levels 1
- The potential for neoplasms, such as leukemia or lymphoma, to cause elevated C3 and C4 1
- The importance of considering other clinical findings and laboratory tests to accurately interpret elevated C3 and C4 levels, as these elevations are often non-specific and can be caused by a variety of conditions.
From the Research
Indications of Elevated C3 and C4
Elevated levels of C3 and C4 can be indicative of various conditions, including:
- Inflammatory bowel disease, such as Crohn's disease 2
- Systemic lupus erythematosus (SLE), although in SLE, C3 and C4 levels are often decreased 3
- COVID-19, with higher levels observed in ICU patients compared to non-ICU patients 4
- Autoimmune diseases, with complement C4 playing a key role in the classical and lectin complement pathways 5
- Depression, with increased levels of complement C3c and C4 observed in unipolar depressed patients 6
Conditions Associated with Elevated C3 and C4
Some conditions associated with elevated C3 and C4 levels include:
- Crohn's disease, with high-normal C3 and C1-INH concentrations having a higher odds ratio for a diagnosis of Crohn's disease compared to ulcerative colitis 2
- COVID-19, with elevated levels of C3, C4, and CH50 observed in both ICU and non-ICU patients 4
- Depression, with increased levels of immunoglobulin IgM, complement C3c, and C4 observed in unipolar depressed patients 6
Laboratory Markers
Elevated C3 and C4 levels can serve as laboratory markers for various conditions, including:
- Distinguishing between Crohn's disease and ulcerative colitis, with measurement of C3, C1-INH, and CRP used as an additional marker 2
- Organ damage in SLE, with serum complement proteins remaining a reliable laboratory marker for nephritis 3
- COVID-19, with elevated levels of C3, C4, and CH50 indicating activation of the innate immune system 4