Complement factors C3, C4 (synonyms: complement C3; C3 complement factor; complement C4; C4 complement factor) are acute-phase proteins and part of the nonspecific humoral immune system. They serve the defense against infections by eliminating cellular antigens (e.g. bacteria). In addition, due to their cell-destructive properties, if they act in an unregulated manner, they can cause tissue damage in the course of many diseases (e.g. glomerulonephritis, systemic lupus erythematosus). The complement system is similar to blood clotting in its activation steps and includes the following functions:
- Increasing vascular permeability through the local action of activated complement factors (anaphylactic effect).
- Attraction of leukocytes (white blood cells) and macrophages (phagocytes) to the site of inflammation (chemotaxis).
- Increasing the phagocytosis effect / scavenging activity of the cell (opsonization; labeling of microorganisms).
- Destruction of invaded pathogens by lysis (“dissolution”), e.g. by the membrane attack complex (MAC).
In the context of classical complement activation, an antigen-antibody complex (cells labeled with antibodies: IgG or IgM) is required. In this process, the complex of classical C3 convertase is formed by cleavage of C2 and C4. Subsequently, complement factor C3 is activated by C3 convertase with cleavage of an alpha fragment. Activated C3b is a potent marker for antigenic cells (opsonization). In the context of alternative complement activation, the process takes place without the aid of antibodies. C3 was thereby activated to C3b by proteases (enzymes that can degrade protein) present in plasma. Low complement C3 at normal C4 levels suggests activation of the alternative complement pathway. Normal C3 and low C4 suggests C1 inhibitor deficiency and C4 defect, respectively.
Procedure
Material Needed
- Fresh serum (frozen in case of prolonged storage).
Preparation of the patient
- Not necessary
Standard values
| Parameter | Standard ranges |
| C3 | 88-228 mg/dl |
| C4 | 16-47 mg/dl |
Indications
- Suspected C3 or C4 complement deficiency.
- Recurrent infections (especially childhood).
- Glomerulonephritides – kidney diseases caused by inflammation of the renal corpuscles.
- Systemic lupus erythematosus (SLE) – autoimmune disease in which there is the formation of autoantibodies. It is one of the collagenoses.
Interpretation
Interpretation of increased values
- Without prognostic relevance (for this, see “Further notes).
- Bacterial diseases (C3, C4 ↑).
Interpretation of lowered values
- Immune complex diseases (correlation with disease activity; C3, C4 ↓).
- Acute pancreatitis (inflammation of the pancreas).
- Autoimmune hemolytic anemia (AIHA) – anemia caused by the appearance of antibodies against the body’s own erythrocytes (red blood cells).
- Dermatoses (skin diseases):
- Bullous pemphigoid (blistering skin disease).
- Pemphigus vulgaris (blistering autoimmune dermatosis).
- Glomerulonephritis (poststreptococcal GN, SLE nephritis), due to complement depletion.
- Collagenoses (inflammatory rheumatic diseases of connective tissue).
- Cryoglobulinemia – chronic recurrent immune complex vasculitides (immune disease of the vessels) characterized by the detection of abnormal cold precipitating serum proteins (cold antibodies).
- Liver parenchymal damage, severe
- Post-infectious vasculitis (inflammation of blood vessels).
- Rheumatoid arthritis
- SLE
- Non-immune complex diseases:
- Chronic inflammation
- Tumors
- Deficiency of complement factor C4
- Hereditary (“hereditary”) C4 deficiency clustered with LE.
- Hereditary angioneurotic edema (HANE); symptoms: recurrent edema (swelling) of the skin, mucous membranes, and internal organs
- C1 inhibitor deficiency
- Alpha1 antitrypsin deficiency
- Sepsis (blood poisoning)
- Transplant rejection
Further notes
- Because complement factors C3, C4 are acute-phase proteins, assessment of these should always be performed in combination with C-reactive protein (CRP). Acute disease may result in falsely normal concentrations of C3 and C4, respectively.
