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 Acute phase protein (Acute Phase Reactants)

Complement C3 and C4 (Complements)




  1. Advised to diagnose angioedema.
  2. To monitor:
    1. The patient with systemic lupus erythematosus nephritis.
    2. In post-streptococcal nephritis.
    3. In membranoproliferative nephritis.


  1. Complements are a group of globulin proteins and acts as an enzyme.
    1. These enzymes facilitate immunological and inflammatory response.
  2. These are heat labile plasma proteins.
  3. These consists of at least 14 protein which has a biological function in the immune system. The more common are labeled as C1 to C9. 
    1. Besides the major components (C1 to C9), there are subcomponent and inhibitors are involved in the system.
  4. The complement acts as an enzyme.
    1. This will help in the immunologic response and inflammation.
    2. They help in the chemotaxis and activation of the WBCs.
    3. There is an increase in the vascular permeability, allowing the Antibody and the WBCs to be delivered at the site of immune complex (Ag+Ab).
    4. Complement helps in the process of phagocytosis and the immune adherence of the antibody to the antigen.
    5. The complement activation leads to lysis of the antigen or the bacteria.
  5. Complement is the biological amplifier.
    1. First, there is activation of the few molecules of C1q.
    2. In the next stage more and more molecules are activated.
    3. In the final stage, there are thousands of molecules.

  1. The classical pathway is activated by the C1 and ultimately there is activation of C1 to C9.
  2. In the alternate pathway, there is a bypass of the C1q and direct activation of C3.
    1. The alternate pathway may be activated by IgA.
    2. This is activated in the absence of the antibody.
    3. Polysaccharides of the bacterial cell wall can activate C3 and leads to the destruction of the bacteria.

  1. In the case of antigen and antibody complexes, the complement is consumed which leads to decreased level of compliments.
  2. Complement deficiency may be:
    1. Congenital like angioedema. There is a congenital lake of a C1 - inhibitor often called C1 esterase.
      1. The Complement system is activated, and the complement is consumed or used up which will lead to falling in the complement level.
    2. Acquired decreased level is seen in the chronic diseases where there is the presence of Ag+Ab complexes leading to overactivation of the complement system, complement is consumed and there is a fall in the level of complement e.g. serum sickness, infectious endocarditis, lupus erythematosus, vasculitis, and glomerulonephritis.


  1. C3 molecular weight is 185 kD with a normal serum level of 1200 µg/mL, acute phase serum level increases 30% and the chromosomal location is 19p13.2-13.3.
  2. C3 after activation is converted into C3a and C3b.
    1. C3a is an anaphylatoxin binds to mast cells and trigger the release of histamine and other mediators products.
      1. This will leads to vasodilation, erythema, and swelling.
      2. This will also lead to bronchoconstriction.
      3. C3a, when injected into the skin, leads to wheel and flare.
    2. C3b attaches to the antigen-antibody complex through C3b receptor on the inflammatory cells and leads to its adherence to the:
      1. Neutrophils.
      2. Basophils.
      3. Eosinophils.
      4. Monocytes.
      5. This will leads to enhance opsonization of the antigen-antibody complex and phagocytosis.
      6. C3b coated particles also activate B-lymphocytes to produce antibody.
      7. In the early phase of viral infection, C3b leads to neutralization of the viruses when the antibody level is limited.
  3. C3 has an important role in the classical and alternative pathways.
  4. This is major opsonin after the activation mainly by C3b.
    1. Any decrease in C3b leads to defective opsonization.
    2. In C3b deficiency, Neisserial infections are very common.

  1. In the case of deficiency, there are recurrent pyogenic infections, particularly due to encapsulated bacteria.
  2. When it occurs in childhood, then there is a recurrent bacterial infection, mainly by the gram-negative bacteria like:
    1. Neisseria meningitidis.
    2. Enterobacter aerogenes.
    3. Escherichia coli.
    4. Haemophilus influenzae.
  3. Infection with gram-positive bacteria may also occur.
  4. C3 deficiency may cause:
    1. Upper and lower respiratory infection including pneumonia.
    2. There are episodes of sinusitis.
      1. Tonsillitis.
      2. Otitis media.
    3. 26% of C3 deficiency patients may develop an autoimmune complex disease like systemic lupus erythematosus.
    4. 26% of C3 deficiency patients develop membranoproliferative or mesangiocapillary glomerulonephritis. 


  1. C4 has a highly pleomorphic gene and located in the HLA complex chromosome 6.
  2. C4 has a molecular weight of 200 kD, normal serum level of 600 µg/mL, acute serum phase increase of 34% and chromosome number 6p21.3.
  3. Partial deficiency of the C4 predisposes to SLE.
  4. Deficiency of C4a and C4b are associated in:
    1. Scleroderma.
    2. IgA associated nephropathy.
    3. Diabetes mellitus.
    4. Chronic hepatitis.
    5. Membranous nephropathy.
    6. Henoch schonlein purpura.
  5. Complete deficiency of the C4 is rare.


Source 1

C3   =  

Source 2 

C4    =  

Source 1

Source 2 

The decreased level of complement (C1 to C9) is seen in:

  1. Congenital as seen in angioedema.
  2. Autoimmune diseases like SLE, serum sickness, rheumatoid arthritis, Sjogren's syndrome, and lupus nephritis.
  3. Malnutrition.
  4. Cirrhosis.
  5. Hepatitis.
  6. Acute kidney transplant rejection.
  7. In case septicemia (sepsis).

The increased level of complements (C1 to C9) is seen in:

  1. Acute rheumatic fever.
  2. Ulcerative colitis.
  3. Acute myocardial infarction.
  4. Malignant tumors.
Acute phase proteins     Acute Inflammation Chronic Inflammation
Albumin decreased decreased
Prealbumin decreased decreased
CRP increased increased
Alpha-1-antitrypsin increased increased
Ceruloplasmin increased increased
Haptoglobin increased increased
Transferrin decreased increased
Fibrinogen increased increased
Complement (C3) increased increased

 Table showing Positive and Negative acute phase protein

Positive acute phase proteins Negative acute phase proteins
Ceruloplasmin Prealbumin
Haptoglobin Albumin
Fibrinogen Transferrin
Complement (C 3, 4)  

Possible References Used

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