Cerebrospinal fluid immunoglobulin kappa light chain in clinically isolated syndrome and multiple sclerosis
Makbule Senel1, Hayrettin Tumani1, Florian Lauda1
1Department of Neurology, University of Ulm, Ulm, Germany.
Insights
Measurement of immunoglobulin kappa free light chains (KFLC) in cerebrospinal fluid (CSF) shows promise for diagnosing multiple sclerosis (MS). While KFLC is a rapid, quantitative test, it is comparable, not superior, to oligoclonal bands (OCB) for early MS diagnosis.
Area of Science:
- Neurology
- Immunology
- Biochemistry
Background:
- Oligoclonal bands (OCB) are crucial for diagnosing multiple sclerosis (MS) and predicting conversion from clinically isolated syndrome (CIS) to MS.
- Current OCB tests are non-quantitative and difficult to standardize.
- Immunoglobulin kappa free light chains (KFLC) offer a potential quantitative and standardized alternative.
Purpose of the Study:
- To evaluate the diagnostic utility of CSF KFLC measurement in patients with MS and CIS.
- To compare the performance of KFLC testing with OCB in early MS diagnosis.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) was used to measure KFLC in CSF and serum of 211 patients.
- Patient groups included those with no inflammatory neurological disease (NIND), MS, viral CNS infections, neuroborreliosis, bacterial CNS infections, and CIS.
- CIS patients were further categorized into those who remained CIS (CIS-CIS) and those who developed MS (CIS-MS) over two years.
Main Results:
- The CSF-serum ratio of KFLC (Q KFLC) was elevated in all MS patients, 86.8% of CIS-MS patients, and 61.5% of CIS-CIS patients.
- Q KFLC was significantly elevated in CIS patients with OCB (p<0.001).
- Q KFLC correlated significantly with CSF leukocyte count, CXCL13 levels, and intrathecal IgG synthesis.
Conclusions:
- CSF KFLC measurement is a rapid, quantitative, and easily standardized diagnostic tool.
- KFLC testing demonstrates diagnostic sensitivity and specificity comparable to OCB for early MS detection.
- While promising, KFLC is not superior to OCB in diagnosing early MS.
Background:
Oligoclonal bands (OCB) are the most widely used CSF test to support the diagnosis of MS and to predict conversion of clinically isolated syndrome (CIS) to multiple sclerosis (MS). Since OCB tests are based on non-quantitative and difficult to standardise techniques, measurement of immunoglobulin kappa free light chains (KFLC) may represent an easier to use quantitative test.
Methods:
KFLC were measured in CSF and serum of 211 patients using ELISA. These include patients without any inflammatory central nervous system reaction (NIND, n = 77), MS (n = 20), viral CNS infections (V-CNS-I, n = 10), neuroborreliosis (NB, n = 17) and other bacterial CNS infections (B-CNS-I, n = 10). Furthermore a cohort of 77 patients with CIS, including 39 patients that remained CIS over follow-up of two years (CIS-CIS) and 38 patients that developed MS over the same follow-up time (CIS-MS).
Results:
CSF-serum ratio of KFLC (Q KFLC) was elevated in all patients with MS, 86.8% of patients with CIS-MS and 61.5% of patients with CIS-CIS. It was significantly elevated in CIS with presence of OCB (p<0.001). Q KFLC significantly correlated with other CSF variables such as CSF leukocyte count (p<0.001, R = 0.46), CSF CXCL13 levels (p<0.001, R = 0.64) and also intrathecal IgG synthesis (p<0.001, R = 0.74) as determined by nephelometry and quotient diagram. OCB were detected in 66.7% of CIS-CIS and in 92.1% of CIS-MS.
Conclusions:
Although the measurement of CSF KFLC is a rapid and quantitative easy to standardize tool, it is almost equal but not superior to OCB with regard to diagnostic sensitivity and specificity in patients with early MS.
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