Validation of kappa free light chains as a diagnostic biomarker in multiple sclerosis and clinically isolated syndrome: A multicenter study

Abstract

These findings further support the diagnostic value of intrathecal KFLC synthesis in CIS and MS patients and demonstrate a valid, easier and rater-independent alternative to OCB detection.

CSF Free Light Chains as a Marker of Intrathecal Immunoglobulin Synthesis in Multiple Sclerosis: A Blood-CSF Barrier Related Evaluation in a Large Cohort

“…In line with previous studies from others and us (17, 18, 26) the present study confirms elevated intrathecal KFLC and LFLC production in patients with MS leading to high diagnostic accuracy. To allow an assessment of the utility and strengths of different FLC measures, we determined not only CSF and serum levels of FLC but also compared various FLC measures including CSF-serum ratio (Q KFLC, Q LFLC), FLC index (KFLC index, LFLC index), and CSF KFLC to LFLC ratio within one large cohort for their diagnostic accuracy in MS.…”

CSF Free Light Chains as a Marker of Intrathecal Immunoglobulin Synthesis in Multiple Sclerosis: A Blood-CSF Barrier Related Evaluation in a Large Cohort

“…In line with previous studies from others and us (17, 18, 26) the present study confirms elevated intrathecal KFLC and LFLC production in patients with MS leading to high diagnostic accuracy. To allow an assessment of the utility and strengths of different FLC measures, we determined not only CSF and serum levels of FLC but also compared various FLC measures including CSF-serum ratio (Q KFLC, Q LFLC), FLC index (KFLC index, LFLC index), and CSF KFLC to LFLC ratio within one large cohort for their diagnostic accuracy in MS.…”

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

“…Conversely, no such a correlation was observed in cases with CSF-restricted o-fLC bands. This demonstrates that compared to the intrathecal fraction, the relative amount of serum-derived fLC fraction in the CSF becomes negligible, which is in line with the recent study of Presslauer et al [8] where fKLC intrathecal fraction was close to 100% in most MS patients. This probably accounts for the fact that simple CSF fLC concentration has similar diagnostic sensitivity and specificity as quotients and indices, although we still recommend the use of the latter because false positive results of CSF fLC may occur in cases of very high serum fLC concentrations (e.g.…”

KFLC-index distinguishes multiple sclerosis from anti-myelin oligodendrocyte glycoprotein and aquaporin 4 diseases in a Chinese cohort

“…The sensitivity of the KFLC-index for MS diagnosis in our cohort was 69%, which is lower than the 88%–96% reported in previous studies from Western countries. This finding aligns with the performance of OCBs, which showed a sensitivity of 80.0% in our study—comparable to the 76.4% reported in a multicentre study from China28—but still below the 82%–93% observed in Western populations 4 9 27 29. The relatively lower sensitivity of the KFLC-index may be influenced by the cut-off value, which is partially dependent on the composition of the control group.…”

CSF Free Light Chains as a Marker of Intrathecal Immunoglobulin Synthesis in Multiple Sclerosis: A Blood-CSF Barrier Related Evaluation in a Large Cohort

“…In line with previous studies from others and us (17, 18, 26) the present study confirms elevated intrathecal KFLC and LFLC production in patients with MS leading to high diagnostic accuracy. To allow an assessment of the utility and strengths of different FLC measures, we determined not only CSF and serum levels of FLC but also compared various FLC measures including CSF-serum ratio (Q KFLC, Q LFLC), FLC index (KFLC index, LFLC index), and CSF KFLC to LFLC ratio within one large cohort for their diagnostic accuracy in MS.…”

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

“…Conversely, no such a correlation was observed in cases with CSF-restricted o-fLC bands. This demonstrates that compared to the intrathecal fraction, the relative amount of serum-derived fLC fraction in the CSF becomes negligible, which is in line with the recent study of Presslauer et al [8] where fKLC intrathecal fraction was close to 100% in most MS patients. This probably accounts for the fact that simple CSF fLC concentration has similar diagnostic sensitivity and specificity as quotients and indices, although we still recommend the use of the latter because false positive results of CSF fLC may occur in cases of very high serum fLC concentrations (e.g.…”

KFLC-index distinguishes multiple sclerosis from anti-myelin oligodendrocyte glycoprotein and aquaporin 4 diseases in a Chinese cohort

“…The sensitivity of the KFLC-index for MS diagnosis in our cohort was 69%, which is lower than the 88%–96% reported in previous studies from Western countries. This finding aligns with the performance of OCBs, which showed a sensitivity of 80.0% in our study—comparable to the 76.4% reported in a multicentre study from China28—but still below the 82%–93% observed in Western populations 4 9 27 29. The relatively lower sensitivity of the KFLC-index may be influenced by the cut-off value, which is partially dependent on the composition of the control group.…”

CSF Free Light Chains as a Marker of Intrathecal Immunoglobulin Synthesis in Multiple Sclerosis: A Blood-CSF Barrier Related Evaluation in a Large Cohort

“…In line with previous studies from others and us (17, 18, 26) the present study confirms elevated intrathecal KFLC and LFLC production in patients with MS leading to high diagnostic accuracy. To allow an assessment of the utility and strengths of different FLC measures, we determined not only CSF and serum levels of FLC but also compared various FLC measures including CSF-serum ratio (Q KFLC, Q LFLC), FLC index (KFLC index, LFLC index), and CSF KFLC to LFLC ratio within one large cohort for their diagnostic accuracy in MS.…”

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

“…Conversely, no such a correlation was observed in cases with CSF-restricted o-fLC bands. This demonstrates that compared to the intrathecal fraction, the relative amount of serum-derived fLC fraction in the CSF becomes negligible, which is in line with the recent study of Presslauer et al [8] where fKLC intrathecal fraction was close to 100% in most MS patients. This probably accounts for the fact that simple CSF fLC concentration has similar diagnostic sensitivity and specificity as quotients and indices, although we still recommend the use of the latter because false positive results of CSF fLC may occur in cases of very high serum fLC concentrations (e.g.…”

KFLC-index distinguishes multiple sclerosis from anti-myelin oligodendrocyte glycoprotein and aquaporin 4 diseases in a Chinese cohort

“…The sensitivity of the KFLC-index for MS diagnosis in our cohort was 69%, which is lower than the 88%–96% reported in previous studies from Western countries. This finding aligns with the performance of OCBs, which showed a sensitivity of 80.0% in our study—comparable to the 76.4% reported in a multicentre study from China28—but still below the 82%–93% observed in Western populations 4 9 27 29. The relatively lower sensitivity of the KFLC-index may be influenced by the cut-off value, which is partially dependent on the composition of the control group.…”