Test Id : KCSF
Immunoglobulin Kappa Free Light Chain, Spinal Fluid
Useful For
Suggests clinical disorders or settings where the test may be helpful
Diagnosing multiple sclerosis and other demyelinating conditions
Evaluating patients who present with a clinically isolated syndrome in which the patient reports symptoms (headaches, optic neuritis, fatigue, and many others, depending on the disease location) characteristic of inflammation and demyelination of the central nervous system
Recommended in cases where the imaging findings are atypical and in populations in which multiple sclerosis is less common (eg, children, older individuals, or non-White populations)
The test is not useful when a clear diagnosis is already known because a positive result does not correlate with severity of the disease or disease outcomes.
Method Name
A short description of the method used to perform the test
Nephelometry
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Aliases
Lists additional common names for a test, as an aid in searching
Free Light Chain, cerebrospinal fluid
Free Light Chain, spinal fluid
Cerebrospinal fluid Free Light Chain
Spinal fluid Free Light Chain
Multiple Sclerosis (MS)
Oligoclonal Banding
Specimen Type
Describes the specimen type validated for testing
CSF
Ordering Guidance
For evaluation of multiple sclerosis. SFIG/ Cerebrospinal Fluid IgG Index Profile, Serum and Spinal Fluid in conjunction with OLIG / Oligoclonal Banding, Serum and Spinal Fluid are available as individually orderable tests.
In addition, a multiple sclerosis cascade (MSP3 / Multiple Sclerosis [MS] Cascade, Serum and Spinal Fluid) is available. This profile starts with immunoglobulin kappa free light chain testing. When that is borderline or elevated, additional testing for oligoclonal banding will be performed and results interpreted accordingly.
Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Specimen Type: Spinal fluid
Container/Tube: Sterile vial
Specimen Volume: 1 mL
Collection Instructions: Label specimen as spinal fluid.
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.
0.5 mL
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
| Gross hemolysis | 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 |
|---|---|---|---|
| CSF | Frozen (preferred) | 28 days | |
| Ambient | 24 hours | ||
| Refrigerated | 72 hours |
Useful For
Suggests clinical disorders or settings where the test may be helpful
Diagnosing multiple sclerosis and other demyelinating conditions
Evaluating patients who present with a clinically isolated syndrome in which the patient reports symptoms (headaches, optic neuritis, fatigue, and many others, depending on the disease location) characteristic of inflammation and demyelination of the central nervous system
Recommended in cases where the imaging findings are atypical and in populations in which multiple sclerosis is less common (eg, children, older individuals, or non-White populations)
The test is not useful when a clear diagnosis is already known because a positive result does not correlate with severity of the disease or disease outcomes.
Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS). The clinical diagnosis of MS is centered on each patient while applying diagnostic guidelines. Immunoglobulin free light chain (FLC) presence in cerebrospinal fluid (CSF) is an alternative for diagnosing MS using nephelometry. Light chains are produced in excess during antibody formation and secreted from plasma cells or plasmablasts. Quantitative FLC assays use antisera directed against epitopes that are exposed only when the light chains are free (unbound to heavy chain) in solution. FLC immunoassays can be used to specifically quantitate FLC even in the presence of large concentrations of polyclonal immunoglobulins.
Routine use of isoelectric focusing electrophoresis coupled with IgG-specific immunoblotting (IgG-IEF) identifies immunoglobulins specific to the CNS. This method is part of the diagnostic criteria used for MS, ie, oligoclonal banding (OLIG / Oligoclonal Banding, Serum and Spinal Fluid). However, oligoclonal banding is a labor-intensive technique that includes subjective interpretation of IgG bands from paired CSF and serum.
This 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 70.4% with a specificity of 86.8%. The differences between this test and the oligoclonal banding analysis are not statistically significant (p=0.20), and the 2 tests show comparable performance. However, this test does not require a paired serum specimen, offers a shorter turnaround-time for results, and an objective quantitative result.
This testing is most useful in patients presenting with a clinically isolated syndrome, which is a clinical episode where patient reports symptoms (headaches, optic neuritis, fatigue, and many others, depending on the disease location) characteristic of inflammation and demyelination of the CNS, and needs to be checked by a neurologist. This is when the likelihood of a diagnosis of MS is greater or most likely but not yet known or confirmed. CSF laboratory testing is also strongly recommended in cases where the imaging findings are atypical and in populations in which MS is less common (eg, children, older individuals, or non-White populations).
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.
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
Interpretation
Provides information to assist in interpretation of the test results
When a 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. 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). If clinically indicated, consider additional CSF testing such as oligoclonal banding by isoelectric focusing and CSF IgG index.
When result is greater than or equal to 0.1000 mg/dL, 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). If clinically indicated, consider additional CSF testing such as oligoclonal banding by isoelectric focusing and CSF IgG index.
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 92.5% clinical sensitivity in the diagnosis of multiple sclerosis.(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 the kappa level 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)
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Supportive Data
The revised 2017 McDonald criteria established detection of at least 2 cerebrospinal fluid (CSF)-specific oligoclonal bands as a substitute for dissemination in time.(3) Dissemination in time means the lesions observed of the central nervous system in imaging studies have to grow over time and that new lesions are expected and confirm disease progression. Before the 2017 revision, patients would wait up to 6 months for a confirmed diagnosis to fulfill the definitive diagnostic criteria for multiple sclerosis.
Based on a published Mayo Clinic study with 325 subjects, this test alone demonstrates comparable performance to OLIG / Oligoclonal Banding, Serum and Spinal Fluid along with increased sensitivity for demyelinating diseases.(1)
A second, larger cohort of over 1300 patient samples analyzed at Mayo Clinic, where 159 participants had demyelinating disease, was reviewed to validate the results of the first study with 325 subjects.
In this larger cohort, the Mayo Clinic OLIG / Oligoclonal Banding, Serum and Spinal Fluid test had a clinical sensitivity of 74% and clinical specificity of 88% when 2 unique CSF bands are used as a cutoff for positive. The 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 (p=0.20). The 2 tests show comparable performance without the need of a paired serum specimen, shorter turn-around-time for results, and an objective quantitative result.(2)
Clinical Reference
Recommendations for in-depth reading of a clinical nature
1. 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(7):1071-1080
2. 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
3. Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. The Lancet Neurology. 2018;17(2):162-173
4. Saadeh R, Pittock S, Bryant S, et al. CSF kappa free light chains as a potential quantitative alternative to oligoclonal bands in multiple sclerosis. American Academy of Neurology Annual Meeting. Philadelphia, PA. 2019
5. Awad A, Hemmer B, Hartung HP, Kieseier B, Bennett JL, Stuve O. Analyses of cerebrospinal fluid in the diagnosis and monitoring of multiple sclerosis. J Neuroimmunol. 2010;219(1-2):1-7
6. Hassan-Smith G, Durant L, Tsentemeidou A, et al. High sensitivity and specificity of elevated cerebrospinal fluid kappa free light chains in suspected multiple sclerosis. J Neuroimmunol. 2014;276(1-2):175-179
7. Presslauer S, Milosavljevic D, Brucke T, et al. Elevated levels of kappa free light chains in CSF support the diagnosis of multiple sclerosis. J Neurol. 2008;255(10):1508-1514
8. Presslauer S, Milosavljevic D, Brucke T, et al. Validation of kappa free light chains as a diagnostic biomarker in multiple sclerosis and clinically isolated syndrome: a multicenter study. Mult Scler. 2016;22(4):502-10
9. Presslauer S, Milosavljevic D, Hubl W, Parigger S, Schneider-Koch G, Bruecke T. Kappa free light chains: Diagnostic and prognostic relevance in MS and CIS. PLoS One. 2014;9(2):e89945
10. Makshakov G, Nazarov V, Kochetova O, Surkova E, Lapin S, Evdoshenko E. Diagnostic and prognostic value of the cerebrospinal fluid concentration of immunoglobulin free light chains in clinically isolated syndrome with conversion to multiple sclerosis. PLoS One. 2015;10(11):e0143375
Method Description
Describes how the test is performed and provides a method-specific reference
In this nephelometric method, the light scattered by the antigen-antibody complexes are 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 by 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)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
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.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
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.
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- 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.
CPT codes are provided by the performing laboratory.
83521
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 |
|---|---|---|
| KCSF | Kappa Free Light Chain, CSF | 48774-4 |
| 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.
|
|---|---|---|
| KCSF | Kappa Free Light Chain, CSF | 48774-4 |