Test Catalog

Test Id : MSP3

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Multiple Sclerosis (MS) Profile, Serum and Spinal Fluid

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Overview

Test Catalog

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

Diagnosing multiple sclerosis, especially helpful in patients with equivocal clinical or radiological findings

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
KCSFP Kappa Free Light Chain, CSF Yes, (KCSF) Yes
XSRM Additional sample for reflex OLIGS No 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
OLIGS Serum Bands Yes, (Order OLIG, submit CSF and Serum) No
OLIGC CSF Bands Yes, (Order OLIG, submit CSF and Serum) No

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

Kappa free light-chain testing will be performed by nephelometry on cerebral spinal fluid (CSF) samples. When kappa free light-chain testing indicates either borderline or positive results (> or =0.0600 mg/dL), the oligoclonal banding tests will be performed at an additional charge. If the time of testing exceeds the specimen stability for oligoclonal banding tests, only kappa free light-chain testing will be performed. Kappa free light-chain testing will only be performed up to specimen stability.

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

KCSFP: Nephelometry

OLIGC, OLIGS: Isoelectric Focusing (IEF) with IgG Immunoblot Detection

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

Multiple Sclerosis Profile

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

Cerebrospinal fluid Free Light Chain

Free Light Chain, cerebrospinal fluid

Free Light Chain, spinal fluid

Multiple Sclerosis (MS)

Oligoclonal Banding

Spinal fluid Free Light Chain

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

Kappa free light-chain testing will be performed by nephelometry on cerebral spinal fluid (CSF) samples. When kappa free light-chain testing indicates either borderline or positive results (> or =0.0600 mg/dL), the oligoclonal banding tests will be performed at an additional charge. If the time of testing exceeds the specimen stability for oligoclonal banding tests, only kappa free light-chain testing will be performed. Kappa free light-chain testing will only be performed up to specimen stability.

Specimen Type
Describes the specimen type validated for testing

CSF

Serum

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

Both serum and spinal fluid are required. Spinal fluid must be obtained within 1 week of serum collection.

 

Specimen Type: Spinal fluid

Container/Tube: Sterile vial

Specimen Volume: 1 mL

Collection Instructions: Label specimen as spinal fluid.

 

Specimen Type: Serum

Collection Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL

Collection Instructions:

1. Centrifuge and aliquot serum into a plastic vial within 2 hours of collection.

2. Label specimen as serum.

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

Forms

If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.

Serum, Spinal fluid: 0.5 mL

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

Gross hemolysis Reject
Gross lipemia OK
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
CSF Frozen (preferred) 14 days
Refrigerated 72 hours
Ambient 24 hours
Serum Frozen (preferred) 14 days
Ambient 14 days
Refrigerated 14 days

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

Diagnosing multiple sclerosis, especially helpful in patients with equivocal clinical or radiological findings

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

Kappa free light-chain testing will be performed by nephelometry on cerebral spinal fluid (CSF) samples. When kappa free light-chain testing indicates either borderline or positive results (> or =0.0600 mg/dL), the oligoclonal banding tests will be performed at an additional charge. If the time of testing exceeds the specimen stability for oligoclonal banding tests, only kappa free light-chain testing will be performed. Kappa free light-chain testing will only be performed up to specimen stability.

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

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease characterized by visual, motor, and sensory disturbances. The diagnosis of MS is dependent on clinical, radiological, and laboratory findings. The detection of increased intrathecal immunoglobulin synthesis is the basis for current diagnostic laboratory tests for MS. These tests include the kappa free light chain detection in cerebrospinal fluid (CSF) and CSF oligoclonal band detection.

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.

KAPPA FREE LIGHT CHAIN

Medical decision point: 0.1000 mg/dL

Positive: > or =0.1000 mg/dL

Borderline: 0.0600 mg/dL-0.0999 mg/dL

Negative <0.0600 mg/dL

 

OLIGOCLONAL BANDS:

<2 bands

Interpretation
Provides information to assist in interpretation of the test results

When result is less than 0.0600 mg/dL, the kappa free light-chain concentration measured in cerebrospinal fluid (CSF) is lower than the threshold associated with demyelinating disease. This is a negative result. Testing for oligoclonal banding is not performed. Clinical correlation is recommended.

 

When result is between 0.0600 and 0.0999 mg/dL, this is a borderline result. These findings are not specific for multiple sclerosis (MS) because CSF-specific immunoglobulin synthesis may also be detected in patients with other neurologic diseases (infectious, inflammatory, cerebrovascular, autoimmune, and paraneoplastic). Clinical correlation is recommended. Automatic reflexing to oligoclonal bands will occur.

 

When result is 0.1000 mg/dL or more, the kappa free light chain concentration measured in CSF is at or greater than the threshold associated with demyelinating disease. This is a positive result. These findings, however, are not specific for MS because CSF-specific immunoglobulin synthesis may also be detected in patients with other neurologic diseases (infectious, inflammatory, cerebrovascular, autoimmune, and paraneoplastic). Clinical correlation is recommended. Automatic reflexing to oligoclonal bands will occur.

 

A Mayo Clinic study published in 2018 with 325 patients suggested that a kappa free light-chain concentration in CSF greater than or equal to 0.06 mg/dL has 92% clinical sensitivity for the diagnosis of MS.(1)

 

A second, larger Mayo Clinic study with 1355 patients published in 2021 showed that a kappa CSF concentration greater than or equal to 0.06 mg/dL had approximately 89% sensitivity. When kappa value was greater than or equal to 0.1 mg/dL, it had similar sensitivity (87%) to the finding of two unique CSF oligoclonal bands (89%).(2)

 

Given the difference in thresholds based on these studies and highest sensitivity at the threshold of 0.06 mg/dL, any CSF kappa free light-chain result greater than or equal to 0.06 mg/dL will reflex to oligoclonal banding when the multiple sclerosis profile test is ordered.

 

When the oligoclonal band assay detects 2 or more unique IgG bands in the CSF, the result is positive.

 

CSF is used in the diagnosis of MS by identifying increased intrathecal IgG synthesis qualitatively (oligoclonal bands). The presence of 2 or more unique CSF oligoclonal bands was reintroduced as one of the diagnostic criteria for MS in the 2017 revised McDonald criteria. These findings, however, are not specific for MS as CSF-specific IgG synthesis may also be found in patients with other neurologic diseases including infectious, inflammatory, cerebrovascular, and paraneoplastic disorders. Clinical correlation is recommended.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Increased intrathecal immunoglobulin synthesis may occur in other inflammatory central nervous system diseases, and therefore, these assays are not specific for multiple sclerosis.

Supportive Data

In a cohort of 1307 patients, where 159 had demyelinating disease, the Mayo Clinic oligoclonal banding test had a clinical sensitivity of 74% and clinical specificity of 89%, area under the ROC curve of 0.813, when 2 or more unique cerebrospinal fluid (CSF) bands are used as a cutoff for positive. This kappa free light chain test, when considered positive at a concentration greater than or equal to 0.1000 mg/dL as a medical decision point, has a sensitivity of 70% with a specificity of 87%. The differences between the 2 tests are not statistically significant and the 2 tests show comparable performance with shorter turn-around-time for results and an objective quantitative result.

 

This panel combines the ease of use and interpretation of the quantitative measurement of kappa free light chains in CSF and allies it to the traditional interpretation of oligoclonal bands for optimized efficiency in laboratory testing for demyelinating diseases and improved test utilization.

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

1. McGinley MP, Goldschmidt CH, Rae-Grant AD: Diagnosis and treatment of multiple sclerosis: A review. JAMA. 2021;325(8):765-779. doi: 10.1001/jama.2020.26858

2. Hegen H, Walde J, Milosavljevic D, et al: Free light chains in the cerebrospinal fluid. Comparison of different methods to determine intrathecal synthesis. Clin Chem Lab Med. 2019;57(10):1574-1586. doi: 10.1515/cclm-2018-1300

3. Thompson AJ, Banwell BL, Barkhof F, et al: Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162-173

4. Gurtner KM, Shosha E, Bryant SC, et al: CSF free light chain identification of demyelinating disease: comparison with oligoclonal banding and other CSF indexes. Clin Chem Lab Med. 2018;56:1071-1080

5. Saadeh RS, Bryant SC, McKeon A, et al: CSF kappa free light chains: cutoff validation for diagnosing multiple sclerosis. Mayo Clin Proc. 2022;97(4):738-751. doi: 10.1016/j.mayocp.2021.09.014

6. Hegen H, Zinganell A, Auer M, Deisenhammer F: The clinical significance of single or double bands in cerebrospinal fluid isoelectric focusing. A retrospective study and systematic review. PLoS One. 2019;14(4):e0215410. doi: 10.1371/journal.pone.0215410

7. Deisenhammer F, Zetterberg H, Fitzner B, Zettl UK: The Cerebrospinal fluid in multiple sclerosis. Front Immunol. 2019;10:726. doi: 10.3389/fimmu.2019.00726

8. Susse M, Hannich M, Petersmann A, et al: Kappa free light chains in cerebrospinal fluid to identify patients with oligoclonal bands. Eur J Neurol. 2018;25(9):1134-1139. doi: 10.1111/ene.13667

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

Kappa Free Light Chain:

Kappa free light chain is measured by nephelometric method in which the light scattered onto the antigen-antibody complexes is measured. The intensity of the measured scattered light is proportional to the amount of antigen-antibody complexes in the sample under certain conditions.

 

Antigen-antibody complexes are formed when a sample containing antigen and the corresponding antiserum are put into a cuvette. A light beam is generated with a light emitting diode , which is transmitted through the cuvette. The light is scattered onto the immuno-complexes that are present. An antigen-antibody complex is formed in the final measurement.

 

The result is calculated by subtracting the value of the final measurement from the initial measurement. The distribution of intensity of the scattered light depends on the ratio of the particle size of the antigen-antibody complexes to the radiated wavelength.(Instruction manual: Siemens Nephelometer II. Siemens, Inc; Version 2.3, 2008; Addendum to the Instruction Manual 2.3, 08/2017)

 

Oligoclonal Banding:

The oligoclonal banding  assay requires paired cerebrospinal fluid (CSF) and serum samples. Unconcentrated CSF and diluted serum are electrophoresed by isoelectric focusing. The separated IgG bands are visualized by an IgG immunoblot, and oligoclonal bands that are present in the CSF and not in the serum are reported. The assay uses reagents from Helena Laboratories.( Saadeh RS, Ramos PA, Algeciras-Schimnich A, Flanagan EP, Pittock SJ, Willrich MA. An Update on Laboratory-Based Diagnostic Biomarkers for Multiple Sclerosis and Beyond. Clin Chem. 2022;68(9):1134-1150. doi:10.1093/clinchem/hvac061)

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.

3 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 account representative. 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 has been modified from the manufacturer's instructions. Its performance characteristics were 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

83916 x2 (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
MSP3 Multiple Sclerosis Profile 100757-4
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.
KCSFP Kappa Free Light Chain, CSF 48774-4
XSRM Additional sample for Reflex OLIGS No LOINC Needed

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

Test Update Resources

Change Type Effective Date
Test Changes - Title 2024-12-19