Oligoclonal free light chains in cerebrospinal fluid as markers of intrathecal inflammation. Comparison with oligoclonal IgG

Abstract

Aims.To compare the sensitivity and specificity of CSF-restricted oligoclonal IgG and free light chains as markers of multiple sclerosis and other inflammatory neurological diseases. Methods. 196 paired CSF and serum samples were examined for oligoclonal IgG and oligoclonal free light chains. The sensitivity and specificity of the tests were calculated and optimal cut-offs for the number of CSF-restricted oligoclonal bands were then determined by analysis of receiver operating characteristic curves. Results. Optimal cut-off values were ≥5 IgG bands for multiple sclerosis, ≥4 IgG bands for inflammatory neurological disease, ≥6 free κ, and ≥2 free λ bands for both purposes. Using these cut-off values, sensitivities and specificities for multiple sclerosis were 83.8% and 91.3% for IgG, 83.8% and 81.0% for free κ , and 67.6% and 75.4% for free λ. For inflammatory neurological disease, sensitivities and specificities were 60.8% and 95.7% for IgG, 69.6% and 92.6% for free κ, and 64.8% and 86.2% for free λ. Conclusions. Although exact cut-off values may vary according to method, reporting borderline results as positive, may compromise the specificity of the test and should be avoided.. The detection of intrathecal free light chain synthesis may be of value especially when the oligoclonal IgG test is negative or borderline, even though its specificity is slightly lower.

Quantitation of free light chains in the cerebrospinal fluid reliably predicts their intrathecal synthesis

“…5 Nevertheless, we proved that CSF fLC quantitation can predict intrathecal fLC synthesis. Although we did not aim at diagnosis-related analysis, it is of note that two patients with CNS inflammation proved positive for both o-fLC, while negative for o-IgG; 19/20 patients with MS or CIS (95%) were both o-IgG and o-fKLC positive and 17 (85%) were also o-fLLC positive.…”

“…5 Samples were then kept frozen at À30 C until quantitative fLC measurements. CSF and serum fKLC and fLLC concentrations were determined on the SPA Plus turbidimetric analyser using dedicated Freelite TM kits (The Binding Site Ltd.) CE marked for CSF analysis (Ref.…”

Assessment of Intrathecal Free Light Chain Synthesis: Comparison of Different Quantitative Methods with the Detection of Oligoclonal Free Light Chains by Isoelectric Focusing and Affinity-Mediated Immunoblotting

“…For oligoclonal fLC detection, an aliquot was kept at +2 to +8°C for up to 20 days. We have previously reported that oligoclonal fLC patterns remain stable during this period [37]. …”

“…After we had succesfully introduced oligoclonal fLC detection [36, 37], we looked for a quantitative method for comparison and possibly monitoring purposes. Our sandwich ELISA, which was developed during several years, is based on the same principle as the o-fLC test [38].…”

Chemiluminescent detection of oligoclonal immunoglobulins after isoelectric focusing and affinity-mediated immunoblotting

“…5,6 ), IgD (ref. 7 ) and free light chains [8][9][10] detection was reported to provide useful additional information. The concentration of IgG in CSF lies between 10 -100 mg/L and IgG can be easily detected by means of chromogenic detection method.…”