SPEP

SPEP works by applying an electric current to a serum sample on a gel or capillary system, causing proteins to migrate based on charge and size, producing a characteristic banding pattern. The normal pattern shows a large albumin peak followed by smaller alpha-1, alpha-2, beta, and gamma globulin peaks. A sharp, narrow spike (M-spike/M-protein) in the gamma region indicates a monoclonal immunoglobulin produced by a clonal plasma cell or B-cell population, classically seen in multiple myeloma, MGUS, Waldenström macroglobulinemia, and plasmacytoma. In contrast, a broad-based increase in the gamma region suggests polyclonal gammopathy, typically from chronic inflammation, infection, liver disease, or autoimmune conditions. Once an M-spike is identified, immunofixation electrophoresis (IFE) or free light chain assay is used to characterize the specific immunoglobulin type (IgG, IgA, IgM) and light chain (kappa/lambda). SPEP can also show reduced albumin in nephrotic syndrome, liver disease, or malnutrition, and alpha-1 band reduction in alpha-1 antitrypsin deficiency. Beta-gamma bridging can be seen in cirrhosis due to increased IgA. Clinically, SPEP is a key initial screening test when multiple myeloma is suspected (e.g., in a patient with bone pain, anemia, renal insufficiency, hypercalcemia — CRAB criteria), though a 24-hour urine protein electrophoresis (UPEP) is also needed to detect Bence Jones proteins (free light chains) that may not elevate serum levels significantly. Bone marrow biopsy and skeletal survey/MRI complete the myeloma workup. On USMLE, SPEP is frequently tested in vignettes involving monoclonal versus polyclonal gammopathy, with interpretation of M-spike size correlating with clinical significance (MGUS <3 g/dL asymptomatic vs. myeloma >3 g/dL with end-organ damage).