Monoclonal Protein Study, Serum
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Serum proteins can be grouped into 5 fractions by protein electrophoresis:
-Albumin, which represents almost two-thirds of the total serum protein
-Alpha-1, composed primarily of alpha-1-antitrypsin (A1AT), an alpha-1-acid glycoprotein
-Alpha-2, composed primarily of alpha-2-macroglobulin and haptoglobin
-Beta, composed primarily of transferrin and complement C3
-Gamma, composed primarily of immunoglobulins (Ig)
The concentration of these fractions and the electrophoretic pattern may be characteristic of diseases such as monoclonal gammopathies, A1AT deficiency disease, nephrotic syndrome, and inflammatory processes associated with infection, liver disease, and autoimmune diseases.
The following algorithms are available in Special Instructions:
-Laboratory Approach to the Diagnosis of Amyloidosis
-Laboratory Screening Tests for Suspected Multiple Myeloma
Also see Diagnosis and Monitoring of Multiple Myeloma in Publications.
Diagnosis of monoclonal gammopathies, when used in conjunction with urine monoclonal studies
Monitoring patients with monoclonal gammopathies
Protein electrophoresis alone is not considered an adequate screen for monoclonal gammopathies
-A characteristic monoclonal band (M-spike) is often found on protein electrophoresis (PEL) in the gamma globulin region and, more rarely, in the beta or alpha-2 regions. The finding of an M-spike, restricted migration, or hypogammaglobulinemic PEL pattern is suggestive of a possible monoclonal protein and should be followed by MPSU / Monoclonal Protein Study, 24 Hour, Urine, which includes immunofixation (IF), to identify the immunoglobulin (Ig) heavy chain and/or light chain.
-A monoclonal IgG or IgA >3 g/dL is consistent with multiple myeloma (MM).
-A monoclonal IgG or IgA <3 g/dL may be consistent with monoclonal gammopathy of undetermined significance (MGUS), primary systemic amyloidosis, early or treated myeloma, as well as a number of other monoclonal gammopathies.
-A monoclonal IgM >3 g/dL is consistent with macroglobulinemia.
-The initial identification of a serum M-spike >1.5 g/dL on PEL should be followed by MPSU / Monoclonal Protein Study, 24 Hour, Urine.
-The initial identification of an IgM, IgA, or IgG M-spike >4 g/dL, >5 g/dL, and >6 g/dL respectively, should be followed by VISCS / Viscosity, Serum.
-After the initial identification of an M-spike, quantitation of the M-spike on follow-up PEL can be used to monitor the monoclonal gammopathy. However, if the monoclonal protein falls within the beta region (most commonly an IgA or an IgM) quantitative immunoglobulin levels may be more a useful tool to follow the monoclonal protein level than PEL. A decrease or increase of the M-spike that is >0.5 g/dL is considered a significant change.
-Patients suspected of having a monoclonal gammopathy may have normal serum PEL patterns. Approximately 11% of patients with MM have a completely normal serum PEL, with the monoclonal protein only identified by IF. Approximately 8% of MM patients have hypogammaglobulinemia without a quantifiable M-spike on PEL but identified by IF. Accordingly, a normal serum PEL does not rule out the disease and PEL should not be used to screen for the disorder. MPSS / Monoclonal Protein Study, Serum, which includes IF, should be done to screen if the clinical suspicion is high.
Other Abnormal PEL Findings:
-A qualitatively normal but elevated gamma fraction (polyclonal hypergammaglobulinemia) is consistent with infection, liver disease, or autoimmune disease.
-A depressed gamma fraction (hypogammaglobulinemia) is consistent with immune deficiency and can also be associated with primary amyloidosis or nephrotic syndrome.
-A decreased albumin (<2 g/dL), increased alpha-2 fraction (>1.2 g/dL), and decreased gamma fraction (<1 g/dL) is consistent with nephritic syndrome and, when seen in an adult older than 40 years, should be followed by MPSU / Monoclonal Protein Study, 24 Hour, Urine.
-In the hereditary deficiency of a protein (eg, agammaglobulinemia, alpha-1-antitrypsin [A1AT] deficiency, hypoalbuminemia), the affected fraction is faint or absent.
-An absent alpha-1 fraction is consistent with A1AT deficiency disease and should be followed by a quantitative A1AT assay (AAT / Alpha-1-Antitrypsin, Serum).
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Very large IgG M-spikes (>4 g/dL) may saturate the protein stain. In these situations, quantitative IgG assays (IGG / Immunoglobulin G [IgG], Serum) should be performed to accurately determine M-spike concentrations to monitor disease progression or response to therapy.
Fibrinogen will migrate as a distinct band in the beta-gamma fraction. Serum specimens from new patients with a beta-gamma band are to be treated with thrombin to ensure complete conversion of fibrinogen.
Hemolysis may augment the beta fraction.
Penicillin may split the albumin band.
Radiographic agents may produce an uninterpretable pattern.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
> or =1 year: 6.3-7.9 g/dL
Reference values have not been established for patients that are <12 months of age.
Albumin: 3.4-4.7 g/dL
Alpha-1-globulin: 0.1-0.3 g/dL
Alpha-2-globulin: 0.6-1.0 g/dL
Beta-globulin: 0.7-1.2 g/dL
Gamma-globulin: 0.6-1.6 g/dL
An interpretive comment is provided with the report.
Reference values have not been established for patients that are <16 years of age.
No monoclonal protein detected
Clinical References Provides recommendations for further in-depth reading of a clinical nature
Kyle RA, Katzmann JA, Lust, JA, Dispenzieri A: Clinical indications and applications of electrophoresis and immunofixation. In Manual of Clinical Laboratory Immunology. Sixth edition. Edited by NR Rose, RG Hamilton, B Derick. Washington, DC. ASM Press, 2002, pp 66-70