Introduction
Kappa free light chains in the CSF as an emerging biomarker
History of FLC detection
Elevated κ-FLC in the CSF of patients with MS
Reference | Type of controlsa | No. of control subjects | No. of MS patients | McDonald criteria | Laboratory method | κ‑FLC index cut-off | Elevated κ‑FLC index in MS, n | Sensitivity, % | Normal κ‑FLC index in controls, n | Specificity, % | OCB positive in MS, n | Sensitivity, % | OCB negative in controls, n | Specificity, % |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
[25] | NIND/IND/PIND | 1149 | 75 | 2010 | Ne/N Latex | 9.58 | 69 | 92 | 1115 | 97 | 71 | 95 | 1072 | 93 |
[26] | 299 | 146 | 2010/2017 | Tu/Freelite | 5.8 | 76 | 52 | 282 | 94 | 54 | 37 | 299 | 100 | |
[28] | 197 | 45 | 2017 | 6.6 | 42 | 93 | 172 | 87 | 40 | 89 | 179 | 91 | ||
[29] | NIND/IND | 105 | 71 | Not specified | Ne/N Latex | 12.3 | 68 | 96 | 105 | 100 | 65 | 92 | 99 | 94 |
[30] | 85 | 37 | Not specified | Ne/Freelite | 5.9 | 28 | 76 | 77 | 91 | 33 | 89 | 69 | 81 | |
[31] | 253 | 67 | 2010 | 10.463 | 58 | 87 | 193 | 76 | 63 | 94 | 187 | 74 | ||
[33] | 83 | 59 | Not specified | Tu/Freelite | 12.45 | 46 | 78 | 64 | 77 | 46 | 78 | 66 | 80 | |
[32] | 258 | 127 | 2017 | Ne/N Latex | 5.0 | 122 | 96 | 208 | 81 | 123 | 97 | 214 | 83 | |
[24] | 219 | 284 | 2005/2010 | Tu/Freelite | 6.6 | 264 | 93 | 181 | 83 | 245 | 86 | 202 | 92 | |
[34] | 42 | 34 | 2017 | 9.4 | 32 | 94 | 29 | 68 | 34 | 100 | 38 | 90 | ||
[35] | 240 | 133 | 2017 | Ne/N Latex | 5.0 | 124 | 93 | 205 | 85 | 127 | 96 | 204 | 85 | |
[27] | 456 | 84 | 2017 | Tu/Freelite | 6.2 | 75 | 89 | 383 | 85 | 71 | 85 | 405 | 89 | |
[36] | NIND | 368 | 41 | 2001/2005 | Ne/Freelite | 5.9 | 40 | 98 | 318 | 86 | 39 | 95 | 338 | 92 |
[23] | 60 | 60 | 2005 | 5.9 | 56 | 93 | 57 | 95 | 56 | 93 | 59 | 98 | ||
[37] | 97 | 96 | 2010 | T/Freelite | 7.5 | 87 | 91 | 88 | 91 | 79 | 82 | 91 | 94 | |
[40] | 30 | 68 | 2017 | N/Freelite | 3.09 | 49 | 72 | 30 | 100 | 38 | 56 | 30 | 100 | |
[38] | 50 | 80 | 2010 | N/N Latex | 5.3 | 77 | 96 | 48 | 96 | 73 | 91 | 49 | 98 | |
[39] | HC/SC | 60 | 62 | 2010 | 7.15 | 56 | 90 | 60 | 100 | 54 | 87 | 60 | 100 |
κ-FLC index associated with early MS disease activity
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 |