Application of κ free light chains in cerebrospinal fluid as a biomarker in multiple sclerosis diagnosis: development
Estefania Valencia-Vera1, Ana Martinez-Escribano Garcia-Ripoll2, Alfredo Enguix2
1Hospital Universitario Virgen de la Victoria, Laboratorio Clinico, Distrito Universitario Teatinos, Campus Teatinos s/n, Málaga 29010, Spain.
Insights
Measuring kappa free light chains (KFLC) in cerebrospinal fluid (CSF) is a viable alternative to oligoclonal bands (OCB) for diagnosing multiple sclerosis (MS). This method can help screen patients and reduce the need for manual OCB testing.
Area of Science:
- Neurology
- Immunology
- Clinical Chemistry
Background:
- Intrathecal synthesis of immunoglobulin is crucial in diagnosing multiple sclerosis (MS) and other demyelinating diseases.
- Current methods like immunoglobulin G oligoclonal bands (OCB) are used to evaluate this synthesis.
- Kappa free light chains (KFLC) in cerebrospinal fluid (CSF) offer a potential alternative diagnostic marker.
Purpose of the Study:
- To assess the diagnostic value of CSF KFLC measurement.
- To evaluate the utility of KFLC in an algorithm alongside OCB interpretation for MS diagnosis.
- To determine the optimal cutoff for KFLC index in identifying MS.
Main Methods:
- A cross-sectional study included 123 patients with CSF OCB requests.
- OCB were detected using isoelectric focusing and immunofixation.
- KFLC were analyzed by nephelometry, and the KFLC index was calculated using CSF/serum quotients. Receiver operating characteristic (ROC) curves and the Youden method were used to find the optimal cutoff.
Main Results:
- CSF KFLC median was significantly higher in the MS group (1.66 mg/L) compared to other CNS diseases (0.10 mg/L).
- The KFLC index showed a significant difference between groups, with ROC analysis yielding 93.94% accuracy.
- An optimal KFLC index cutoff of 2.91 demonstrated 83.78% sensitivity and 85.88% specificity for MS diagnosis. The proposed algorithm achieved 89.19% sensitivity and 84.71% specificity.
Conclusions:
- KFLC determination is a rapid, automated method for evaluating intrathecal immunoglobulin synthesis.
- While not superior in sensitivity or specificity to OCB for MS diagnosis, KFLC serves as an effective screening tool.
- Implementing KFLC testing can potentially reduce the number of manual OCB tests required.
Background:
The determination of κ free light chains (KFLC) in cerebrospinal fluid (CSF) by nephelometry is a feasible alternative to immunoglobulin G oligoclonal bands (OCB) in the evaluation of intrathecal synthesis of immunoglobulin in multiple sclerosis (MS) and other demyelinating diseases. The aim of this study was to assess the diagnostic value of KFLC and its inclusion in a procedure algorithm along with OCB interpretation.
Methods:
A cross-sectional study, which included 123 patients with a CSF OCB request, was carried out. Isoelectric focusing followed by immunofixation was used to detect OCB, and nephelometry was used to analyze KFLC. The KFLC index was calculated using CSF/serum quotient of KFLC and albumin. The KFLC index was compared with MS diagnosis to find the optimal cutoff. It was obtained from the receiver operating characteristic (ROC) curves and the Youden method.
Results:
The CSF KFLC median was 1.66 mg/L in the MS group, whereas in other central nervous system diseases, KFLC showed generally no or only moderate increase in CSF (median 0.10 mg/L). KFLC index showed a significant difference between groups. ROC analysis for CSF KFLC concentration, and KFLC indexes were 91.88% and 93.94%, respectively. The best cutoff for the KFLC index was 2.91 for MS diagnosis (sensitivity: 83.78%; specificity: 85.88%). The proposed algorithm showed high sensitivity (89.19%) and specificity (84.71%).
Conclusions:
KFLC determination is rapid and automatized, but it has no higher sensitivity and specificity than OCB in MS diagnosis. Nevertheless, when used in screening, it could reduce the number of manual OCB tests.
