Serum Protein Electrophoresis (SPEP) is a laboratory test that analyzes proteins present in the liquid part of the blood, called serum. The test separates these proteins based on their electrical charge and size, revealing a pattern that can indicate various diseases. This separation allows clinicians to screen for and monitor conditions affecting protein production or loss. SPEP is a diagnostic tool used particularly when blood or immune system disorders are suspected.
Understanding the Five Protein Fractions
The technique of electrophoresis involves placing a small sample of serum onto a supportive medium and applying an electric current. Proteins migrate at different speeds based on their electrical charge and size, separating the hundreds of serum proteins into five distinct fractions that are measured and analyzed.
The fastest-moving and most abundant fraction is Albumin, constituting over half of the total serum protein. Albumin maintains the body’s fluid balance and transports substances like hormones and medications. Following Albumin are the globulin fractions: Alpha-1, Alpha-2, Beta, and Gamma, which contain various other functional proteins.
The Globulin Fractions
The Alpha-1 fraction contains proteins like alpha-1 antitrypsin, involved in regulating inflammation. The Alpha-2 fraction includes haptoglobin, which binds free hemoglobin, and alpha-2 macroglobulin, a large protease inhibitor. The Beta fraction is composed of transport proteins such as transferrin (which moves iron) and lipoproteins (responsible for fat transport). The Gamma fraction is the most significant immunologically, primarily consisting of immunoglobulins, also known as antibodies.
Diseases Identified by Abnormal Gamma Globulins
Abnormalities in the Gamma globulin region are often the most clinically significant finding, pointing to immune system disorders. This region contains antibodies produced by plasma cells. An abnormal pattern is usually categorized as either a monoclonal or a polyclonal gammopathy.
A monoclonal gammopathy is characterized by a sharp, narrow peak, known as an “M-spike” or “M-protein.” This indicates the overproduction of a single, identical type of antibody, signifying a clonal disorder. The M-spike is the hallmark finding for Multiple Myeloma, a plasma cell cancer where malignant cells produce massive amounts of non-functional antibody.
Monoclonal Gammopathy of Undetermined Significance (MGUS) is a common, non-cancerous condition also presenting with an M-spike, but at a lower concentration and without the organ damage seen in myeloma. Differentiating between these conditions requires further testing, but SPEP serves as the initial screening tool. Waldenstrom Macroglobulinemia, a rare type of lymphoma, also results in a monoclonal spike, typically composed of the large immunoglobulin M (IgM) antibody.
In contrast, a polyclonal gammopathy appears as a broad, diffuse elevation or “hump” across the entire gamma region. This pattern represents a generalized immune response where many different plasma cell clones produce a wide range of antibodies. Polyclonal elevations are seen in chronic inflammatory conditions like rheumatoid arthritis, systemic lupus erythematosus, and chronic infections, such as viral hepatitis. The distinction between a sharp monoclonal spike and a broad polyclonal elevation is a crucial step in diagnosing the underlying disease process.
Other Conditions Affecting Protein Patterns
Changes in protein fractions other than gamma globulins provide diagnostic clues for various non-immune system diseases. The Albumin fraction frequently decreases in severe Liver Disease, such as cirrhosis, because the liver is the primary site of albumin synthesis. Liver damage compromises the ability to produce this protein, resulting in low serum albumin levels.
In advanced liver disease, a unique pattern called “beta-gamma bridging” may appear, where the beta and gamma peaks merge. This pattern is caused by a massive increase in certain immunoglobulins, often suggesting cirrhosis. Kidney Disease, particularly Nephrotic Syndrome, causes significant protein loss, resulting in a sharp drop in serum Albumin as it leaks into the urine.
In kidney disorders, a compensatory increase is often seen in the Alpha-2 globulin fraction. This elevation is due to the retention of large proteins, such as alpha-2 macroglobulin, which are too big to pass through the damaged kidney filter. Furthermore, elevated Alpha-1 and Alpha-2 fractions suggest Acute Inflammation or infection, as these fractions contain acute phase reactants that increase rapidly in response to insult.