Test Catalog

Test Id : DMOGA

Monoclonal Gammopathy, Diagnostic, Serum

Useful For
Suggests clinical disorders or settings where the test may be helpful

Screening and diagnosis of monoclonal gammopathies including analysis of free light chains

 

Assessing the risk of progression from monoclonal gammopathy of undetermined significance to multiple myeloma

Profile Information
A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.

Test Id Reporting Name Available Separately Always Performed
TMAB Therapeutic Antibody Administered? No Yes
TPE Total Protein Yes, (Order TP) Yes
SPE Protein Electrophoresis No Yes
MPTS M-protein Isotype MALDI-TOF MS, S Yes, (Order MALD) Yes
KFLCS Kappa Free Light Chain, S Yes, (Order FLCS) Yes
LFLCS Lambda Free Light Chain, S Yes, (Order FLCS) Yes
KLRS Kappa/Lambda FLC Ratio Yes, (Order FLCS) Yes

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
IFXED Immunofixation Delta and Epsilon, S Yes No

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This test includes total protein, serum protein electrophoresis, heavy and light chain typing (kappa and lambda), and quantitation of kappa and lambda free light chains.

 

If a light chain is identified without a corresponding heavy chain during initial testing, immunofixation with IgD and IgE antisera will be performed at an additional charge.

 

For more information, see Multiple Myeloma: Laboratory Screening.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

TPE: Colorimetric; Biuret

SPE: Agarose Gel Electrophoresis

MPTS: Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS)

KFLCS, LFLCS: Turbidimetry

KLRS: Calculation

IFXED: Immunofixation

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Monoclonal Gammopathy Diagnostic, S

Aliases
Lists additional common names for a test, as an aid in searching

Amyloid

Free light chain ratio

Immunofixation

Immunosubtraction

Kappa free light chain

Lambda free light chain

Light chain deposition disease

M-protein

Mass Fix

MGUS

MGUS Follow-up

MGUS screen

miRAMM

Multiple Myeloma

Myeloma

Myeloma screen

POEMS

Protein electrophoresis

Serum protein electrophoresis

SPEP

Mass-Fix

DMOGA

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This test includes total protein, serum protein electrophoresis, heavy and light chain typing (kappa and lambda), and quantitation of kappa and lambda free light chains.

 

If a light chain is identified without a corresponding heavy chain during initial testing, immunofixation with IgD and IgE antisera will be performed at an additional charge.

 

For more information, see Multiple Myeloma: Laboratory Screening.

Specimen Type
Describes the specimen type validated for testing

Serum

Ordering Guidance

To monitor a patient with an established diagnosis of a monoclonal gammopathy, order TMOGA / Monoclonal Gammopathy, Monitoring, Serum.

ORDER QUESTIONS AND ANSWERS

Question ID Description Answers
TMAB Therapeutic Antibody Administered?

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation: Fasting (12 hour) preferred but not required

Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Specimen Volume: 2 mL

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:

 

Renal Diagnostics Test Request (T830)

Hematopathology/Cytogenetics Test Request (T726)

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

1.5 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis OK
Gross lipemia Reject
Gross icterus OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 14 days
Frozen 14 days
Ambient 72 hours

Useful For
Suggests clinical disorders or settings where the test may be helpful

Screening and diagnosis of monoclonal gammopathies including analysis of free light chains

 

Assessing the risk of progression from monoclonal gammopathy of undetermined significance to multiple myeloma

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This test includes total protein, serum protein electrophoresis, heavy and light chain typing (kappa and lambda), and quantitation of kappa and lambda free light chains.

 

If a light chain is identified without a corresponding heavy chain during initial testing, immunofixation with IgD and IgE antisera will be performed at an additional charge.

 

For more information, see Multiple Myeloma: Laboratory Screening.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Monoclonal proteins are markers of plasma cell proliferative disorders. The International Myeloma Working Group guidelines state that to adequately screen for a monoclonal protein, serum protein electrophoresis (SPE), immunofixation electrophoresis, and a serum free light chain (FLC) analysis should all be used. If amyloidosis is suspected, a 24-hour urine monoclonal protein study should be performed.

 

The detection of M-proteins by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) has shown to be more analytically and clinically sensitive than immunofixation. In addition, the MALDI-TOF method can detect glycosylated light chains that have been demonstrated to be a risk factor for amyloidosis.

 

This expanded monoclonal protein testing panel provides the highest diagnostic sensitivity for the monoclonal light chain diseases such as primary amyloidosis and light chain deposition disease; disorders that often do not have serum monoclonal proteins in high enough concentration to be detected and quantitated by SPE. The FLC assay is specific for free kappa and lambda light chains and does not recognize light chains bound to intact immunoglobulin.

 

Monoclonal gammopathies may be present in a wide spectrum of diseases that include malignancies of plasma cells or B lymphocytes (multiple myeloma: MM, macroglobulinemia, plasmacytoma, B-cell lymphoma), disorders of monoclonal protein structure (primary amyloid, light chain deposition disease, cryoglobulinemia), and apparently benign, premalignant conditions (monoclonal gammopathy of undetermined significance: MGUS, smoldering MM). While the identification of the monoclonal gammopathy is a laboratory diagnosis, the specific clinical diagnosis is dependent on a number of other laboratory and clinical assessments.

 

If a monoclonal protein pattern is detected by MALDI-TOF MS, immunofixation electrophoresis (IFE), or FLC, a diagnosis of a monoclonal gammopathy is established. Once a monoclonal gammopathy has been diagnosed, the size of the clonal abnormality can be monitored by SPE or FLC and, in some instances, by quantitative immunoglobulins. In addition, if the patient is asymptomatic and has a diagnosis of MGUS, the monoclonal gammopathy screen provides the information (size of M-spike, monoclonal protein isotype, FLC kappa/lambda ratio) needed for a MGUS progression risk assessment (see Interpretation).

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.

TOTAL PROTEIN:

> or =1 year: 6.3-7.9 g/dL

Reference values have not been established for patients that are <12 months of age.

 

PROTEIN ELECTROPHORESIS

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.

 

M-PROTEIN ISOTYPE MALDI-TOF MS

No monoclonal protein detected

 

M-protein Isotype MALDI-TOF MS Flag

Negative

 

KAPPA-FREE LIGHT CHAIN

0.33-1.94 mg/dL

 

LAMBDA-FREE LIGHT CHAIN

0.57-2.63 mg/dL

 

KAPPA/LAMBDA-FREE LIGHT-CHAIN RATIO

0.26-1.65

Interpretation
Provides information to assist in interpretation of the test results

Monoclonal Gammopathies:

-A characteristic monoclonal band (M-spike) is often found on serum protein electrophoresis (SPE) 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 SPE pattern is suggestive of a possible monoclonal protein. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) is performed to identify any immunoglobulin heavy and light chains present.

-A monoclonal IgG or IgA of greater than 3 g/dL is consistent with multiple myeloma (MM).

-A monoclonal IgG or IgA of less than 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 of greater than 3 g/dL is consistent with macroglobulinemia.

-An abnormal serum free light chain (FLC) kappa/lambda (K/L) ratio in the presence of a normal MALDI-TOF MS suggests a monoclonal light chain process and should be followed by MPSU / Monoclonal Protein Study, 24 Hour, Urine.

-The initial identification of a serum M-spike greater than 1.5 g/dL on SPE should be followed by MPSU / Monoclonal Protein Study, 24 Hour, Urine.

-The initial identification of an IgM, IgA, or IgG M-spike greater than 4 g/dL, greater than 5 g/dL, and greater than 6 g/dL, respectively, a VISCS / Viscosity, Serum should be tested to rule out hyperviscosity syndrome.

 

After the initial identification of a monoclonal band, quantitation of the M-spike on follow-up SPE 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 a more useful tool to follow the monoclonal protein level than SPE. A decrease or increase of the M-spike that is greater than 0.5 g/dL is considered a significant change.

 

Patients with monoclonal light chain diseases who have no serum or urine M-spike may be monitored with the serum FLC value.

 

Patients suspected of having a monoclonal gammopathy may have normal serum SPE patterns. Approximately 11% of patients with MM have a completely normal serum SPE, with the monoclonal protein only identified by MALDI-TOF MS. Approximately 8% of MM patients have hypogammaglobulinemia without a quantifiable M-spike on SPE but identified by MALDI-TOF MS or FLC. Accordingly, a normal serum SPE does not rule out the disease and SPE alone should not be used to screen for the disorder if the clinical suspicion is high.

 

MGUS Prognosis:

-Low-risk MGUS patients are defined as having an M-spike of less than 1.5 g/dL, IgG monoclonal protein, and a normal FLC K/L ratio (0.25-1.65), and these patients have a lifetime risk of progression to MM of less than 5%.

-High-risk MGUS patients (M-spike >1.5, IgA or IgM, abnormal FLC ratio) have a lifetime risk of progression to MM of 60%.

 

Other Abnormal SPE 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 (>1.1 g/dL), and decreased gamma fraction (<1 g/dL) is consistent with nephrotic 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

Serum protein electrophoresis (SPE) alone is not considered an adequate screen for monoclonal gammopathies.

 

Very large IgG M-spikes (>4 g/dL) may saturate the protein stain. In these situations, quantitative IgG assays more accurately determine M-spike concentrations for monitoring disease progression or response to therapy.

 

Although the SPE M-spike is the recommended method of monitoring monoclonal gammopathies, IgA and IgM proteins that are contained in the beta fraction may be more accurately monitored by quantitative immunoglobulins.

 

Fibrinogen will migrate as a distinct band in the beta-gamma fraction but will be negative on immunofixation electrophoresis.

 

Hemolysis may augment the beta fraction.

 

Penicillin may split the albumin band.

 

Radiographic agents may produce an uninterpretable pattern.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Rajkumar SV, Kyle RA, Therneau TM, et al: Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood. 2005;106:812-817

2. Katzmann JA, Dispenzieri A, Kyle RA, et al: Elimination of the need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assays. Mayo Clin Proc. 2006;81(12):1575-1578

3. Mills JR, Kohlhagen MC, Dasari S, et al: Comprehensive assessment of M-proteins using nanobody enrichment coupled to MALDI-TOF mass spectrometry. Clin Chem. 2016;62(10):1334-1344

4. Milani P, Murray DL, Barnidge DR, et al: The utility of MASS-FIX to detect and monitor monoclonal proteins in the clinic. Am J Hematol. 2017;92(8):772-779 doi: 10.1002/ajh.24772

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Total Protein:

Divalent copper reacts in alkaline solution with protein peptide bonds to form the characteristic purple-colored biuret complex. Sodium potassium tartrate prevents the precipitation of copper hydroxide and potassium iodide prevents autoreduction of copper. The color intensity is directly proportional to the protein concentration which can be determined photometrically.(Package insert: TP2 cobas. Roche Diagnostics; V 12.0, 11/2019)

 

Electrophoresis:

Serum proteins are separated in an electric field according to their size, shape, and electric charge. The separation is performed on agarose gels. The proteins are visualized by staining with acid blue and the intensity of staining is quantitated by densitometry. Multiplying by the serum total protein converts the percentage of protein in each fraction into serum concentration.(Instruction manual: Helena SPIFE Touch. Helena Laboratories, Corp; 11/2016; package insert: Helena SPIFE Touch SPE Pro 277. Helena Laboratories, Corp; 06/2018)

 

M-protein isotype:

M-protein isotype by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) is performed with immunoaffinity purification followed by MALDI-TOF MS analysis. For the immunoaffinity purification, patient serum is applied to 5 separate immunoaffinity resins (CaptureSelect, Life Sciences) specific to immunoglobulin G, A, M, K, and L. Unbound protein is washed away and the isolated immunoglobulins are broken down in to their reduced to separate the heavy and light chains subunits to be analyzed via MALDI-TOF mass spectrometry. The 5 separate spectra from each patient immunopurification are overlaid and investigated for the overabundance of an immunoglobulin and/or immunoglobulin light chain.(Kohlhagen M, Dasari S, Willrich M, et al: Automation and validation of a MALDI-TOF MS (Mass-Fix) replacement of immunofixation electrophoresis in the clinical lab. Clin Chem Lab Med. 2020 Aug 3;59(1):155-163.  doi: 10.1515/cclm-2020-0581)

 

Free Light Chains:

The determination of the soluble antigen concentration by turbidimetric methods involves the reaction with specific antiserum to form insoluble complexes. When light is passed through the suspension formed a portion of the light is transmitted and focused onto a photodiode by an optical lens system. The amount of transmitted light is indirectly proportional to the specific protein concentration in the test sample. Concentrations are automatically calculated by reference to a calibrations curve stored within the instrument.(Package inserts: Optilite Freelite Kappa Free Kit. The Binding Site Group, Ltd; 06/2015; Optilite Freelite Lambda Free Kit. The Binding Site Group, Ltd; 06/2015)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

2 to 5 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

14 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

83521 x 2

84155

84165

0077U

86334 (if appropriate)

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
DMOGA Monoclonal Gammopathy Diagnostic, S 90992-9
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
TPE Total Protein 2885-2
602837 Albumin 2862-1
602838 Alpha-1 Globulin 2865-4
602839 Alpha-2 Globulin 2868-8
602840 Beta-Globulin 2871-2
602841 Gamma-Globulin 2874-6
602842 A/G Ratio 44429-9
602843 M spike 51435-6
602844 M spike 35559-4
602836 Impression 49296-7
65198 M-protein Isotype MALDI-TOF MS 90990-3
606976 Flag, M-protein Isotype 94400-9
LFLCS Lambda Free Light Chain, S 33944-0
KLRS Kappa/Lambda FLC Ratio 48378-4
TMAB Therapeutic Antibody Administered? 98855-0
KFLCS Kappa Free Light Chain, S 36916-5

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports