Special Protein Testing in The Clinical Laboratory - Part Three

Special Protein Testing in The Clinical Laboratory - Part Three

Welcome to part three 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 with our overview of the proteins most commonly considered in clinical testing.

Immunoglobulins (IgA, IgD, IgE, IgG and IgM): The immunoglobulins, or antibodies, are the most significant gammaglobulins, although some immunoglobulins are not gammaglobulins, and some gammaglobulins are not immunoglobulins. Immunoglobulins are glycoprotein molecules produced by white blood cells. They are a critical part of the immune response because they recognize, bind and help to destroy antigens like bacteria and viruses. The antibody immune response is highly complex and exceedingly specific. Immunoglobulin isotypes differ in their biological features, structure, target specificity and distribution. Hence, assessment of the immunoglobulin isotype can provide useful insight into complex humoral immune response. The antibodies produced by plasma cells are classified by isotype that vary in function and antigen responses, mainly due to structure variability. The five major isotypes identified in humans are IgA, IgD, IgE, IgG and IgM.

IgA is the chief immunoglobulin class of sero-mucous secretions, part of the defense system for external body surfaces. The monomeric form is composed of two alpha heavy chains and two light chains. Two subclasses of IgA—IgA1 and IgA2—have been identified in humans. Normal IgA serum levels vary with age. High IgA serum levels are associated with breastfeeding, chronic infections, liver disease and myeloma. Reduced levels are typically seen in immunodeficiency conditions.

IgD is a functionally significant protein. Its precise role is unknown, although there are indications that it functions principally as a cell– surface antigen receptor (triggering lymphocyte differentiation) and as a ligand for IgD receptors on immune-regulatory helper T-cells. While IgD accounts for less than 1% of total plasma immunoglobulin concentration, its levels are influenced by age and inheritance.

Very high serum IgD concentrations are found in IgD myeloma patients and in hyperimmunoglobulinemia D syndrome (HIDS), an autosomal recessive disorder characterized by recurrent febrile attacks with abdominal, articular and skin manifestations.

IgE, found in trace amounts in the blood, can be used to diagnose allergic diseases. While IgE is typically the least abundant immunoglobulin (only 0.05% of total immunoglobulin concentration), it is capable of initiating the most powerful inflammatory reactions.

IgG typically constitutes approximately 75% of total serum immunoglobulin. Within the IgG class, the usual order of concentration of the four subclasses is IgG1, IgG2, IgG3 and IgG4, but the actual concentration of each may vary markedly among individuals. There are considerable differences in the properties of IgG subclasses, including the ability to fix complement, bind to macrophages and pass through the placenta.

Abnormal levels of one or more subclasses may be associated with conditions like anaphylaxis, autoimmune and gut diseases and hypo- and hypergammaglobulinemia. In particular, reduced production of IgG2 in children may be associated with recurrent infections.

IgM Antibody structure

Diagram demonstrating the pentamic structure of IgM

IgM is the first class of immunoglobulin synthesized in response to antigenic attack. This large, multivalent molecule deals most efficiently with polyvalent antigens such as bacteria and viruses. IgM also activates complement. On active immunization, IgM rapidly appears in sera, but levels normally drop after a week, usually in parallel with an increase in IgG. Normal serum levels are dependent on age. Elevated serum levels are associated with hepatitis, myeloma, Waldenstrom macroglobulinemia and other infections. Reduced levels can occur in antibody-deficiency syndrome.

In part 4 we look at prealbumin among other proteins, and conclude the article.


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/