Plasma contains a very large number of proteins, many of which are present only in trace amounts. The ones that have their main physiological role in plasma have three main functions:
• osmotic regulation
• transport of ligands such as hormones, metal ions, bilirubin, fatty acids, vitamins and drugs
• response to infection or foreign bodies entering the body.
All plasma proteins are synthesised in the liver, with the exception of the immunoglobulins, which are synthesised in the bone marrow. Plasma proteins are readily separated by electrophoresis and this technique forms the basis of several clinical diagnostic tests. The tests are normally recorded subjectively, but a densitometer may be used to obtain a semi-quantitative result.
Albumin
Albumin is the most common plasma protein, constituting some 50% of all plasma protein. Its half-life in plasma is about 20 days, and in a good nutritional state the liver produces about 15 g albumin per day to replace this loss. Albumin is the main regulator of the osmotic pressure of plasma, but also acts as a transporter of haem, bilirubin (a metabolite of haem), biliverdin (a metabolite of bilirubin), free fatty acids, steroids and metal ions (e.g. Cu2+, Fe3+). Some drugs also bind to albumin. Other specific transport proteins found in plasma include steroid-binding proteins such as cortisol-binding globulin, sex-hormone-binding globulin (androgens and oestrogens) and metal-binding proteins, e.g. caeruloplasmin (Cu2+) and transferrin (Fe3+). Other transport plasma proteins include thyroid-binding globulin (thyroxine T4 and triiodo thyronine T3) and haptoglobin (haemoglobin).
Immunoglobulins
Immunoglobulins are synthesised in bone marrow in response to the exposure to a specific foreign body. Immunoglobulins share a common Y-shaped structure of two heavy and two light chains, the light chains (κ, λ) forming the upper arms of the Y. The class of immunoglobulin is determined by the heavy chain that gives rise to fi ve types – IgG, IgA, IgM, IgD and IgE.
IgG accounts for approximately 75% of the immunoglobulins present in the plasma of adults and has a half-life of approximately 22 days. It is present in extra-cellular fluids and appears to eliminate small proteins through aggregation and the reticuloendothelial system. IgA is the secretory immunoglobulin protecting the mucosal surfaces. IgA is synthesised by mucosal cells and represents approximately 10% of plasma immunoglobulins and has a half-life of 6 days. It is found in bronchial and intestinal secretions and is a major component of colostrum (the form of milk produced by the mammary gland immediately after giving birth). IgA is the primary immunological barrier against pathogenic invasion of the mucosal membranes. IgM is found in the intravascular space and its role is to eliminate circulating microorganisms and antigens. IgM accounts for about 8% of plasma immunoglobulins and has a half-life of 5 days. IgM is the fi rst antibody to be synthesised after an antigenic challenge. IgD and IgE are minor immunoglobulins whose roles are not clear since a deficiency of either seems to be associated with no obvious pathology. IgE plays a major part in allergy and may be significantly raised in situations of allergic response, for example in hay fever and atopic eczema.
Myeloma
Myeloma, also called multiple myeloma, is a malignant pathology of plasma cells in which there is an unregulated replication of a single β-cell clone in the bone marrow that proliferates and effectively behaves as a tumour. The cells produce large quantities of a single protein, which migrates as a single dense band in the γ -globulin region during electrophoresis of a serum sample. The protein is called the paraprotein and thus belongs to the class of immunoglobulins with two light chains and two heavy chains. Some myelomas produce an excess of light chains that appear in the serum, and, due to their small size, also in the urine. They are detected by electrophoresis and are referred to as Bence Jones proteins. Their presence is typically a cause of great concern as it indicates that the cell line may be more aggressive and replicating faster than in the case of exclusive appearance of the paraprotein. In rare cases of myeloma, the marrow cells only produce light chains.
Acute Phase Response
Following a stimulus of tissue injury or infection, the body will respond by producing an acute phase response characterised by the release of a number of acute phase proteins from the liver, which is detectable by a change in the pattern of plasma protein electrophoresis. The acute phase response registers as an increased synthesis of some proteins such as α -1-antitrypsin, a proteinase inhibitor that down-regulates inflammation, fibrinogen and C-reactive protein ( CRP). These are referred to as positive acute phase proteins . There will also be a decrease in the production of other proteins such as albumin and transferrin. These are known as negative acute phase proteins . The clinical measurement of acute phase proteins, particularly CRP, by immuno- turbidimetry is widely used as a marker of inflammation in a variety of clinical conditions.
