Test Catalog

Test ID: KCSF    
Immunoglobulin Kappa Free Light Chain, Spinal Fluid

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

Diagnosis of multiple sclerosis and other demyelinating conditions

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 individual patient, while applying diagnostic guidelines. Immunoglobulin free light chain (FLC) presence in cerebrospinal fluid (CSF) is an alternative for diagnosis of MS using nephelometry. Light chains are produced in excess during antibody formation and secreted from the plasma-cells or plasma-blasts. 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 in cases of MS, i.e., oligoclonal banding (OLIG). However, OLIG / Oligoclonal Banding, Serum and Spinal Fluid is a labor-intensive technique that includes subjective interpretation of IgG bands from paired CSF and serum. This test (KCSF), when considered positive at a concentration greater than or equal to 0.1000 mg/dL as a medical decision point, has a sensitivity of 67% with a specificity of 86%. The differences between this test (KCSF) and the OLIG analysis are not statistically significant (p=0.083) 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.

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

Interpretation Provides information to assist in interpretation of the test results

When result is less than 0.1000 mg/dL, the kappa free light chain concentration measured in CSF is lower than the threshold associated with demyelinating disease. This is a negative result. Clinical correlation recommended.        

 

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 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 recommended.

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

No significant cautionary statements

Supportive Data

Mayo Clinic currently uses a cutoff of 4 unique bands in cerebrospinal fluid (CSF) for a positive oligoclonal banding (OLIG) test. In the original validation data, 20 patients with definite multiple sclerosis (MS) were compared to 51 non-MS cases. The 4 band cutoff provided a clinical sensitivity of 90% and clinical specificity of 94%.(2) The McDonald revised criteria states that diagnosis of demyelinating disease can be assumed when 2 unique bands are found in CSF using the OLIG test.(1)

 

In a retrospective cohort of 683 patients analyzed in 2018, where 88 had demyelinating disease, the Mayo Clinic OLIG test had a clinical sensitivity of 74% and clinical specificity of 88%, ROC AUC of 0.806, when 2 unique CSF bands are used as a cutoff for positive. 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 67% with a specificity of 86%. The differences between the 2 tests are not statistically significant (p=0.083) and the 2 tests show comparable performance without the need of a paired serum specimen for KCSF, shorter turn-around-time for results, and an objective quantitative result.

 

Based on a published Mayo Clinic study with 325 subjects, this test (KCSF) alone demonstrates comparable performance to OLIG along with increased sensitivity for demyelinating diseases.(3) Replacing an OLIG test with this KCSF test would alleviate the need for serum and CSF IgG and albumin, and calculated conversions.

 

After this initial study, a second larger cohort was used to validate KCSF with a larger number of samples.(4) This study found that in comparison to the current standards of detecting 2 unique CSF OLIG, KCSF at a value greater than or equal to 0.1000 mg/dL showed comparable sensitivity and specificity to OLIG to support diagnosis of MS. KCSF offers a standardized quantitative measure with a single CSF sample without the need of paired serum, with comparable sensitivity and specificity.

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

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

2. Fortini AS, Sanders EL, Weinshenker BG, Katzmann JA: Cerebrospinal fluid oligoclonal bands in the diagnosis of multiple sclerosis. Isoelectric focusing with IgG immunoblotting compared with high-resolution agarose gel electrophoresis and cerebrospinal fluid IgG index. Am J Clin Pathol 2003;120:672-675

3. 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

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, et al: Analyses of cerebrospinal fluid in the diagnosis and monitoring of multiple sclerosis. J Neuroimmunol 2010;219:1-7

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;276:175-179

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;255:1508-1514

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. MSJ 2016;22(4):502-510

9. Presslauer S, Milosavljevic D, Hubl W, et al: Kappa Free Light Chains: Diagnostic and Prognostic Relevance in MS and CIS. PLoS ONE 2014;9(2):e89945

10. Presslauer S, Milosavljevic D, Hubl W, et al: Kappa Free Light Chains: Diagnostic and Prognostic Relevance in MS and CIS. PLoS ONE 2014;9(2):e89945

11. Makshakov G, Nazarov V, Kochetova O, et al: 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