Serum Protein Electrophoresis

Serum protein electrophoresis (SPE)

Laboratory technique that separates serum proteins based on electrical charge to evaluate protein abnormalities, especially monoclonal gammopathies

SPE fractions

Albumin, alpha-1, alpha-2, beta-1, beta-2, and gamma regions seen on serum protein electrophoresis

Albumin fraction

Largest peak on SPE representing albumin synthesized by the liver and responsible for oncotic pressure and transport

Alpha-1 fraction

Region containing alpha-1 antitrypsin and other acute phase proteins

Alpha-2 fraction

Region containing haptoglobin and alpha-2 macroglobulin, often increased in inflammation

Beta-1 fraction

Region containing transferrin, which transports iron

Beta-2 fraction

Region containing complement C3 and fibrinogen if plasma contamination is present

Gamma fraction

Region containing immunoglobulins including IgG, IgA, and IgM

Hypoalbuminemia

Decreased albumin peak on SPE due to decreased synthesis, increased loss, or increased metabolism

Causes of hypoalbuminemia

Cirrhosis, hepatitis, inflammation, nephrotic syndrome, burns, GI protein loss, thyrotoxicosis, and severe inflammation

Acute inflammation SPE pattern

Increased alpha-1 and alpha-2 regions due to acute phase reactants with mild albumin decrease

Alpha-1 antitrypsin

Acute phase reactant that increases in the alpha-1 region during acute inflammation

Haptoglobin

Acute phase reactant that increases in the alpha-2 region during inflammation and binds free hemoglobin

Chronic inflammation SPE pattern

Decreased albumin with polyclonal increase in the gamma region

Polyclonal gammopathy

Broad-based increase in gamma region caused by many different antibody-producing plasma cell clones

Hypergammaglobulinemia

Increased gamma region due to polyclonal immunoglobulin production

Causes of polyclonal hypergammaglobulinemia

Chronic inflammation, autoimmune disease, hepatic disease, and AIDS

Hypogammaglobulinemia

Decreased or absent gamma region due to reduced immunoglobulin production

Causes of hypogammaglobulinemia

Primary immunodeficiency, immunosuppressive therapy, or light-chain myeloma

Oligoclonal pattern

Presence of multiple narrow bands in the gamma region representing limited antibody clones

Causes of oligoclonal pattern

Autoimmune disease, viral antibody responses, and transplant patients on immunosuppression

Hemolysis SPE finding

Extra bands in the alpha-2 region caused by hemoglobin–haptoglobin complexes

Fibrinogen contamination

Sharp peak in the beta-2 region indicating plasma or incompletely clotted serum

Beta-gamma bridging

Loss of separation between beta and gamma regions commonly seen in alcoholic cirrhosis

Monoclonal gammopathy

Presence of a single clone of plasma cells producing identical immunoglobulin protein

M protein

Monoclonal immunoglobulin or free light chain produced by a plasma cell clone

M spike

Sharp, narrow peak on SPE representing a monoclonal protein

Multiple myeloma

Malignant plasma cell disorder with high M protein levels and end-organ damage

SPE pattern in multiple myeloma

Sharp monoclonal spike usually in gamma region with suppression of normal immunoglobulins

MGUS

Monoclonal gammopathy of undetermined significance with low M protein and no organ damage

SMM

Smoldering multiple myeloma characterized by higher M protein and plasma cells but no CRAB features

Difference between MGUS and MM

MGUS lacks CRAB features and requires monitoring, while MM causes organ damage and requires treatment

Difference between SMM and MM

SMM has no CRAB features but higher risk of progression compared to MGUS

Types of M proteins

IgG, IgA, IgM, free kappa light chains, or free lambda light chains

Bence Jones protein

Free immunoglobulin light chains produced by plasma cells, often detected in urine

Free light chain myeloma

Myeloma that produces only light chains without intact immunoglobulins

Kappa and lambda ratio

Measurement used to detect monoclonal light chain production and assess disease progression

CRAB

Acronym describing myeloma-related organ damage: hyperCalcemia, Renal insufficiency, Anemia, Bone lesions

ROTI

Myeloma-related organ and tissue impairment indicating active disease

Hypercalcemia in MM

Result of bone destruction releasing calcium into the bloodstream

Renal insufficiency in MM

Kidney damage caused by light chain deposition and high protein load

Anemia in MM

Reduced red blood cell production due to bone marrow infiltration

Bone lesions in MM

Lytic lesions caused by plasma cell destruction of bone

Initial MM screening test

Serum protein electrophoresis to detect an M spike

Quantitative immunoglobulin testing

Measurement of IgG, IgA, IgM, and free light chains to assess monoclonal production

Immunofixation electrophoresis

Technique used to identify the specific heavy and light chain of a monoclonal protein

Penta screen

Screening immunofixation test that detects monoclonality but does not identify protein type

Light chain only immunofixation pattern

Kappa or lambda restriction without corresponding IgG, IgA, or IgM band

Monitoring MM treatment response

Evaluated by changes in M protein concentration and free light chain ratios over time

Complete response in MM

Normalization of free light chain ratio with no detectable M protein

Partial response in MM

At least 50% decrease in serum M protein concentration