Protein Electrophoresis, Serum

CPT: 84155; 84165
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Test Details

Synonyms

  • Electrophoresis, Serum

Test Includes

Graph with relative percentages and quantitation of albumin, α1, α2, β, and γ-globulin fractions, and total protein; quantitation of M-spike if present

Use

A principal use of this test is in the detection of monoclonal gammopathies. These are usually found in association with hemic neoplasms, especially multiple myeloma. They also occur in other benign and malignant conditions. Any such protein detected should be identified by an alternative technique, such as immunofixation or immunoelectrophoresis.

Other applications of serum protein electrophoresis include the following:

• Serum protein evaluation, nutritional status.

• Work-up for liver disease, including cirrhosis and chronic active hepatitis. In liver disease, albumin is apt to be decreased. A2 may be low. γ is often polyclonal (ie, dome-shaped) in many cases of cirrhosis. The normal depression between β and γ area may be missing in hepatic cirrhosis; this is called beta-gamma bridging. Polyclonal gammopathy occurs in a wide range of entities which have in common chronic immunologic stimulation (eg, sarcoidosis).

• The γ-globulin may present an isolated increase. The γ-globulin fraction includes IgG, IgA, IgM, IgD, and IgE. Diffuse polyclonal elevation indicates a chronic immunologic process such as that found with liver disease (eg, chronic active hepatitis, cirrhosis), collagen diseases (eg, systemic LE, rheumatoid arthritis), neoplasms (eg, some instances of Hodgkin disease), and chronic myelomonocytic leukemia. Several small bands (oligoclonal) are seen in patients with hepatitis, immune complex diseases, acquired immunodeficiency syndrome, and angioimmunoblastic lymphoadenopathy.

Monoclonal gammopathy (M protein) patterns may be benign, especially when small and not increasing, but monoclonal gammopathies relate especially to myeloma, primary amyloidosis, macroglobulinemia of Waldenström, and occasional malignant lymphomas. These are tall, narrow, spire-shaped formations as seen in densitometer tracings. Although small monoclonal gammopathies may be found with benign diseases, they may also be detected with early or evolving plasma cell dyscrasias or malignant lymphoproliferative diseases. Therefore, such small monoclonal gammopathies are regarded as “monoclonal gammopathies of undetermined significance.” All patients with monoclonal gammopathies should be followed with periodic serum protein electrophoresis to differentiate stable from increasing M spikes. Increasing M proteins require further evaluation (bone marrow examination, skeletal x-ray studies, urinary protein electrophoresis, immunoelectrophoretic or immunofixation studies, and so forth).

Low γ-globulin: Although gamma globulins may decrease slightly with advancing age, any decrease below the normal range if unexplained by obvious causes of protein loss (such as known renal disease), should be further evaluated with a urine immunofixation to detect possible monoclonal free light chains (Bence Jones protein) in the urine. Hypogammaglobulinemia is also seen in many patients with B-cell lymphoproliferative disorders such as chronic lymphocytic leukemia. They may be decreased with cytotoxic or immunosuppressive drug therapy (long-term steroid use, antineoplastic chemotherapy), malignant lymphoproliferative diseases, and plasma cell dyscrasias (multiple myeloma), and adult common variable immunodeficiency syndrome. If there is clinical history of susceptibility to infection in the patient or the family, then quantitative immunodiffusion or nephelometric assay for IgG, IgA, and IgM may prove helpful. Attention to lymphocytes in the peripheral blood film, presence or absence of hepatosplenomegaly and in patients over age 40, presence or absence of light chains in urine immunoelectrophoresis or immunofixation may be relevant (eg, light chain disease).

High α2: A2 includes inflammation-reactive fractions, and may be increased with neoplasms (eg, renal cell carcinomas), acute infections, rheumatic fever, arteritis, nephrotic syndromes, and other inflammatory states. A2-macroglobulin is increased in pregnancy and with diabetes mellitus. Healthy children may have higher levels of α2-macroglobulin than adults.

Low α2: One of the important fractions of α2 is haptoglobin. Depression of haptoglobin may indicate hemolysis. A2-globulins may be decreased in hepatocellular damage. Trauma and transfusions may cause a drop in α2.

A1 globulins are increased in active inflammatory or neoplastic diseases.

Low α1 or flat α1 curve: α1-antitrypsin is responsible for 90% of serine antiprotease activity in serum. Its deficiency is due to a genetic abnormality that must be investigated because it leads to emphysema and cirrhosis. If the patient has emphysema, a family history of emphysema, or liver disease of uncertain type, α1-antitrypsin assay and phenotype may be indicated.

Albumin is better measured by electrophoresis than by chemical methods when is is relevant to do so. Electrophoresis permits diagnosis of rare entities such as analbuminemia and bisalbuminemia. Albumin is increased in dehydration and decreased in a wide variety of subacute, subchronic, and chronic diseases including liver, renal, and gastrointestinal diseases, malnutrition, and cachexia.

Decreased total protein with essentially normal pattern might indicate dietary deficiency or hemodilution (IV fluid running at time of venipuncture?)

Significantly elevated total protein with essentially normal pattern is likely to be secondary to dehydration.

Significantly low total protein and albumin, increased α2, and low γ is prototypical of the nephrotic syndrome.

Limitations

In the evaluation of multiple myeloma (MM), 12% of patients will not be detected by SPEP.1 The addition of serum free light chains (sFLC) and IFE increases detection of MM to >99% and is consistent with the International Myeloma Working Group recommended guidelines.2 (In Related Information, see profile 120256 Immunofixation (IFE), Serum, Protein Electrophoresis (PE), Serum, and Quantitative Free κ and λ Light Chains (FLC) Plus Ratio, Serum.)

Methodology

Electrophoresis on agarose media

Reference Interval

See tables.

Serum Protein Electrophoresis (SPE)

Test

Age

Reference Interval

Albumin

0 to 30 d

Not established

>30 d

2.9−4.4 g/dL

α1-Globulin

0 to 30 d

Not established

>30 d

0.0−0.4 g/dL

α2-Globulin

0 to 30 d

Not established

>30 d

0.4−1.0 g/dL

β-Globulin

0 to 30 d

Not established

1 to 6 m

0.5−1.3 g/dL

>6 m

0.7−1.3 g/dL

γ-Globulin

0 to 30 d

Not established

1 to 6 m

0.3−1.6 g/dL

7 m to 5 y

0.4−1.3 g/dL

6 to 17 y

0.6−1.5 g/dL

>17 y

0.4−1.8 g/dL

Total Protein

0 to 6 m

4.6−7.2 g/dL

7 m to 1 y

5.7−8.2 g/dL

>1 y

6.0−8.5 g/dL

Globulin

0 to 30 d

Not established

>30 d

2.2−3.9 g/dL

A:G Ratio

0 to 30 d

Not established

>30 d

0.7−1.7 g/dL

Serum Protein Electrophoresis Interpretation

Pattern Description

Electrophoretic Zones

Total Protein

(g/dL)

Albumin

(g/dL)

α1

(g/dL)

α2

(g/dL)

β

(g/dL)

γ

(g/dL)

N = normal level.

+ = elevated.

– = decreased.

N+ = normal to elevated.

N– = normal to decreased.

–N+ = decreased to normal to elevated.

Normal

N

N

N

N

N

N

Hemolysis

α2/β bridging

Protein-losing syndromes

N+

N+

N–

–N+

Nephrotic syndrome

N

+++

N

N–

Hypogammaglobulinemia

N–

N

N

N

N

Agammaglobulinemia

N–

N

N

N

N

Absent

Diffuse hepatocellular degeneration

N–

N+

Polyclonal gammopathy

N+

N–

N

N

N

+

Chronic inflammatory response

N+

N–

N+

+

N

+

Acute inflammatory response

N

N–

+

+

N

N–

Subacute inflammatory response

N

N–

N

+

N

N

Hepatic cirrhosis

–N+

N

N–

β/γ bridging

Hypo-α1-globulinemia

N

N

N

N

N

Monoclonal gammopathy (γ)

N+

N–

N

N

N

(M-spike)

Monoclonal gammopathy (β)

N+

N–

N

N

(M-spike)

N–

Biclonal gammopathy (γ, β, or both)

N+

N–

N

N

(M-spike)

(M-spike)

Oligoclonal bands

N

N–

N+

N+

N

Oligo banding

Bisalbuminemia

Split peak

Hypoalbuminemia

N–

N

N

N

N

Additional Information

Absolute values (g/dL), instead of relative percentages (%), should be used for interpretation.

Specimen Requirements

Specimen

Serum

Volume

2 mL

Minimum Volume

1 mL

Container

Red-top tube or gel-barrier tube

Storage Instructions

Refrigerate at 2°C to 8°C.

Stability Requirements

Temperature

Period

Room temperature

3 days

Refrigerated

14 days

Frozen

14 days

Freeze/thaw cycles

Stable x3

Causes for Rejection

Hemolysis; plasma instead of serum

Clinical Information

Footnotes

1. Katzmann JA, Kyle RA, Benson J, et al. Screening panels for detection of monoclonal gammopathies. Clin Chem. 2009 Aug;55(8):1517-1522.19520758
2. Dispenzieri A, Kyle R, Merlini G, et al. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia. 2009 Feb;23(2):215-224.19020545

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
001487 Protein Electro.,S 001073 Protein, Total g/dL 2885-2
001487 Protein Electro.,S 001488 Albumin g/dL 2862-1
001487 Protein Electro.,S 001489 Alpha-1-Globulin g/dL 2865-4
001487 Protein Electro.,S 001490 Alpha-2-Globulin g/dL 2868-8
001487 Protein Electro.,S 001491 Beta Globulin g/dL 2871-2
001487 Protein Electro.,S 001492 Gamma Globulin g/dL 2874-6
001487 Protein Electro.,S 001493 M-Spike g/dL 33358-3
001487 Protein Electro.,S 011052 Globulin, Total g/dL 10834-0
001487 Protein Electro.,S 011149 A/G Ratio 1759-0
001487 Protein Electro.,S 011150 Please note: 77202-0
001487 Protein Electro.,S 001498 PDF 11502-2

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