Table 2.
Prognostic value of κ‑free light chain index in patients with multiple sclerosis
| Ref | Age (years) mean ±SD |
Fem. (%) |
McDonald criteria |
OCB (%) |
FU (months) median |
End- point |
Patients reaching endpoint | Patients not reaching endpoint | Assay | Cut-off κ‑FLC index |
Statistical analyses | Main findings | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No. | κ‑FLC index | OCB | No. | κ‑FLC index | OCB | |||||||||||||||
| Positive N | Sensitivity % | Positive N | Sensitivity % | Negative N | Specificity % | Negative N | Specificity % | |||||||||||||
| [51] | NA | NA | 2001 | NA |
55 (mean) |
Conv. to CDMS | 24 | 10 | 42 | NA | NA | 0 | – | – | – | – | Ne/Freelite | > 50 |
Mann Whitney U |
Time to CDMS did not differ between patients with high (> 50) and low (< 50) κ‑FLC index |
| [48] |
35 (min 15–max 62) |
88 | NA | 62 | >24 | Conv. to CDMS | 38 | 35 | 92 | NA | NA | 39 | 25 | 64 | NA | NA | Ne/Freelite | > 10.62 |
Cox regression |
κ‑FLC index predicted time to CDMS (HR 5.3) |
| [50] | 34 ± 11 | 64 | 2017 | 92 |
47 (mean) |
MSSS | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
Ne/ N latex |
NA |
Linear regression |
κ‑FLC index predicted MSSS |
| [47] | 42 ± 11 | 78 | 2010 | NA | 39 | Conv. to MSa | 12 | 12 | 100 | NA | NA | 11 | 3 | 27 | NA | NA | Ne/Freelite | ≥10.6 |
Cox regression |
κ‑FLC index predicted time to MS (50% of patients with κ‑index ≥ 10.6 converting in 21 months) |
| [49] | 30 ± 9 | 86 | 2017 | 82 | 79 | EDSS progressionb | 18 | NA | NA | 17 | 94 | 10 | NA | NA | 4 | 40 | Ne/Freelite | NA |
Spearman correlation |
κ‑FLC index correlated with shorter time to EDSS progression (r = −0.55) |
| Conv. to CDMS | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | κ‑FLC index correlated with shorter time to CDMS (r = −0.59) | |||||||||
| [52] | 33 ± 10 | 68 | 2017 | 90 | 47 | Conv. to CDMS | 38 | 13 | 34 | – | – | 50 | 44 | 88 | – | – |
Ne/ N latex |
> 100 |
Cox regression |
κ‑FLC index predicted time to CDMS (11 vs. 36 months in patients with high [>100] vs. low [≤ 100] κ‑FLC index) Predictive value of κ‑FLC index was superior to that of OCB |
| 36 | 95 | 36 | 95 | 10 | 20 | 7 | 14 | ≥ 6.6 | ||||||||||||
| EDSS ≥ 3 | 8 | 2 | 25 | – | – | 78 | 61 | 78 | – | – | > 100 |
Mann Whitney U |
κ‑FLC index did not differ between patients reaching EDSS ≥ 3 or not at the end of follow-up | |||||||
| 7 | 88 | 8 | 100 | 11 | 14 | 9 | 12 | ≥ 6.6 | ||||||||||||
A search of the electronic database PubMed was performed on November 17, 2021 using the terms “multiple sclerosis” AND “free light chains” AND “prognosis”, “predict” or “conversion” limited to the time period between January 1, 2005 and November 17, 2021. Titles and abstracts of identified articles written in English were screened and the full text of potentially relevant articles were assessed for inclusion criteria. Studies were included if they were original articles investigating the prognostic value of κ‑FLC index in patients with clinically isolated syndrome in terms of various endpoints (e.g., conversion to MS) and used nephelometry/turbidimetry for κ‑FLC measurement. Following original articles were included: [51] Presslauer 2014, [48] Menéndez-Valladares 2015, [50] Vecchio 2019, [47] Gaetani 2020, [49] Salavisa 2020 and [52] Berek 2021
CDMS clinically definite multiple sclerosis, Conv. conversion, EDSS Expanded Disability Status Scale, Fem. females, FLC free light chain, FU follow-up, HR hazard ratio, MSSS Multiple Sclerosis Severity Score, MS multiple sclerosis, N nephelometry, NA not available, No. number, OCB oligoclonal bands, ref reference, SD standard deviation
aConversion to MS was defined by clinical or radiological means
bEDSS progression was defined as an increase in EDSS score of ⩾ 1.5 points from a baseline EDSS score of 0, ⩾ 1.0 point from a baseline EDSS score of 1.0–5.5, or ⩾ 0.5 point from a baseline EDSS score ⩾ 6.0, confirmed after 6 months of follow-up