Special Protein Testing in The Clinical Laboratory - Part Two

Special Protein Testing in The Clinical Laboratory - Part Two

Welcome to part two of our look into the world of special protein testing in a clinical laboratory setting.

Over the coming weeks we will be posting excerpts from an article written by Bob Janetschek, MS, MT (ASCP), our Immunologicals Business Manager for the USA East Coast and Canadian territories.

Join us as we continue our overview of the proteins most commonly considered in clinical testing.

Anti-streptolysin O: Group A β-hemolytic streptococci produce a number of exotoxins that can act as antigens. One of these, streptolysin-O, leads to the production of specific antibodies in infected subjects, increasing the serum concentration of anti-streptolysin O (ASO). This can be used to establish the degree of past and present infection by β-hemolytic streptococci.

Measurement of ASO levels in sera, in conjunction with other laboratory and clinical findings, is useful in diagnosis of diseases caused by streptococcal infections, including rheumatic fever, scarlet fever, glomerulonephritis, tonsillitis and other upper respiratory infections.

Beta (β)-2-microglobulin: Measurement of β-2-microglobulin aids in the diagnosis of kidney disease. This low-molecular-weight protein is found on the surface of most nucleated cells and is eliminated via the kidneys. Following filtration through the glomeruli, it is reabsorbed and catabolized by the proximal tubular cells. Normally, only trace amounts are excreted in urine; this is markedly increased in renal-tubular disorders.

Elevated serum levels of β-2-microglobulin can also occur with rheumatoid arthritis, systemic lupus erythematosus, malignant lymphoma and myelomas.

Ceruloplasmin: Synthesized in the liver, ceruloplasmin plays a major role in copper metabolism, carrying approximately 95% of the total copper in sera. Decreased levels of ceruloplasmin can be caused by hereditary disorders of copper metabolism. In Menkes disease, for example, the body is unable to transport oxidized copper from the gastrointestinal epithelium into the circulation; Wilson’s disease is characterized by the inability to insert oxidized copper (Cu2+) into the developing ceruloplasmin molecule. Dietary copper insufficiency, including malabsorption, also reduces serum ceruloplasmin concentrations. These concentrations may increase as a result of acute-phase reactions, pregnancy or the useof oral contraceptives.

Complement: The complement system enhances (complements) the ability of antibodies and phagocytic cells to clear pathogens from the body. It is part of the body’s innate immune system, which is not adaptable and does not change over the course of an individual’s lifetime.

The complement system consists of a number of small proteins found in the blood, synthesized by the liver and normally circulating as inactive precursors. When stimulated by one of several triggers, enzymes in the system cleave specific proteins to release cytokines and initiate an amplifying cascade of further cleavages. The end result of this complement activation, or complement fixation cascade, is massive amplification of the response and activation of the cell-killing membrane attack complex.

More than 30 different proteins and protein fragments make up the complement system, accounting for about 10% of the globulin fraction of blood. C3 is the major protein component of the complement system, and has a fundamental role in the inflammatory response and immune system functionality. Deficiencies in C3 are typically seen in liver disease,

in severe recurrent infections such as pneumococcal and meningococcal infections and in glomerulonephritis. Elevated serum C3 concentrations, as well as complement levels, are indicative of acute inflammatory reactions and other chronic inflammatory conditions, like rheumatoid arthritis. Another component of the complement system, C4, plays a fundamental role in inflammatory response and immune system functionality.

C4 is reduced with severe liver failure; recurrent staphylococcal and streptococcal infections; and immune complex disorders such as glomerulonephritis, vasculitis and endocarditis.

C-reactive protein: Levels of the acute-phase protein C-reactive protein (CRP) increase in response to inflammation. CRP is present in the sera of normal individuals, and elevated levels can indicate infection, tissue injury, inflammatory disorders and associated diseases. Levels of CRP have been used in a variety of population subgroups to assess cardiovascular risk and myocardial infarction. A complete clinical history is required for accurate interpretation of CRP levels, as levels within the normal range may be affected by a number of factors and should always be compared to previous values.

Cystatin C: Measurements of cystatin C aid in the diagnosis and treatment of renal diseases. Cystatin C is produced by all nucleated cells at a constant rate, is freely filtered by the glomerulus and is almost completely reabsorbed and degraded by the proximal tubular cells. The production rate of cystatin C is not affected by age, gender, muscle mass or inflammatory processes. This makes it an ideal marker of glomerular filtration rate (GFR), since a reduction in GFR results in an increase in cystatin C concentrations. Several studies have shown that cystatin C is a better marker for GFR than serum creatinine levels.

Ferritin: Ferritin, an intracellular protein that stores and releases iron in a controlled manner, is produced by almost all living organisms. In humans, it acts as a buffer against both iron deficiency and overload.

Ferritin is found in most tissues as a cytosolic protein, but small amounts are secreted into sera, where it functions as an iron carrier. Ferritin levels are indirect markers of the total amount of iron stored in the body, and are thus used as a diagnostic test for iron-deficiency anemia and for those undergoing iron therapies.

Haptoglobin: Measurement of haptoglobin levels is useful in the diagnosis of hemolytic diseases related to the formation of hemoglobin–haptoglobin complexes. Haptoglobin is an acid α-2 acute-phase plasma glycoprotein that binds specifically to free plasma oxyhemoglobin. As a result, the high-molecular-weight complex formed prevents hemoglobin filtering by the kidneys. Low levels of haptoglobin are typically associated with hemolytic anemias and liver disease, while elevated levels can develop in response to inflammatory conditions.

In part 3 we will be considering the role of immunoglobulins.


Excerpt taken from the article "Special Protein Testing in the Clinical Laboratory: Overview of Available Assays" published in American Laboratory magazine, August 2016.

Reference link: http://www.americanlaboratory.com/