Table 4B.
Overview inflammatory biomarkers investigated in multiple studies and found to be associated with progression across the MS spectrum.
| Biomarker | Study | Quality | Cohort (n) | Age (y) | EDSS | Follow-up cohorts | Associated clinical outcome measure (follow-up time): statistical analysis | Result |
|---|---|---|---|---|---|---|---|---|
| κ-FLC | Voortman, 2017 | L | CIS (48) | NR | NR | Converters (23) Non-converters (25) |
BL CSF levels in Converters (57.6m) | Similar to Non-converters |
| Makshakov, 2015 | L | CIS (139) | 32.0 33.0 |
NR NR |
Converters (98) Non-converters (41) |
BL CSF levels in Converters (24m) | Higher than Non-converters | |
| κ-FLC index | Vecchio, 2020 | M | RIS+CIS (18) | 36.3 | NR | Converters (6) Non-converters (12) |
BL CSF levels in Converters (43.2m) | Higher than Non-converters |
| Risk of conversion (43.2m) | HR = 1.070 | |||||||
| Gaetani, 2020 | L | CIS (23) | 41.8 | 1.7 | Converters (12) Non-converters (7) |
Time to conversion (39.1m): κ-FLC index > 10.6 (n = 19) |
C-statistic = 0.630 | |
| κ-FLC / Λ-FLC ratio | Rathbone, 2018 | L | CIS (43) | 45.0 | NR | Converters (NR) Non-converters (NR) |
BL CSF levels in Converters (60m) (n = 29) |
Similar to Non-converters |
| Voortman, 2017 | L | CIS (48) | NR | NR | Converters (23) Non-converters (25) |
BL CSF levels in Converters (57.6m) | Lower than Non-converters | |
| Risk of conversion 57.6m): κ / Λ ratio ≤ 3.38 | HR = 2.890 | |||||||
| Likelihood of conversion (57.6m): κ / Λ ratio ≤ 3.38 | OR = 4.860 | |||||||
| Λ-FLC | Voortman, 2017 | L | CIS (48) | NR | NR | Converters (23) Non-converters (25) |
BL CSF levels in Converters (57.6m) | Similar to Non-converters |
| Makshakov, 2015 | L | CIS (139) | 32.0 33.0 |
NR NR |
Converters (98) Non-converters (41) |
BL CSF levels in Converters (24m) | Higher than Non-converters | |
| YKL-40 (CHI3L1) | De Fino, 2019 | L | CIS (25) | 37.4 | 1.3 | Converters (10) Non-converters (14) |
BL CSF levels in Converters (24m) (n = 24) |
Higher than Non-converters |
| ROC (24m): Converters vs. Non-converters (n = 24) |
AUC = 0.790 | |||||||
| Gil-Perotin, 2019 | M | RRMS (99) | 35.0 | 2.0 | Converters (14) Non-converters (85) |
Risk of conversion (52.8m): SPMS ° | HR = 18.040 | |
| Thouvenot, 2019 | L | RIS (71) | 38.0 | NR | Converters (20) Non-converters (51) |
BL CSF levels in Converters (16m) | Similar to Non-converters | |
| Risk of conversion (16m): YKL-40 > 154.6 mg/ml | HR = 2.130 | |||||||
| Risk of conversion (16m): YKL-40 > 154.6 mg/ml ° | HR = 1.560 | |||||||
| Borras, 2016 | L | CIS (50) | 33.0 38.0 |
NR NR |
Converters (25) Non-converters (25) |
BL CSF levels in Converters (49.2m) | Higher than Non-converters | |
| Comabella, 2010 | L | CIS (84) | 26.8 28.7 |
NR NR |
Converters (48) Non-converters (36) |
BL CSF levels in Converters (66m) | Higher than Non-converters | |
| Time to conversion (66m): YKL-40 > 287.9 mg/ml | Shorter than YKL-40 < 287.9 mg/ml | |||||||
| Risk of conversion (66m): YKL-40 > 287.9 mg/ml | HR = 2.500 | |||||||
| CIS (52) | 33.6 36.5 |
NR NR |
Converters (26) Non-converters (26) |
BL CSF levels in Converters (58.8m) | Higher than Non-converters | |||
| CXCL13 | Olesen, 2019 | L | ON (40) | 41.5 39.3 |
NR NR |
Converters (16) Non-converters (24) |
BL CSF levels in Converters (28.2m) | Higher than Non-converters |
| Likelihood of conversion (28.2m): CXCL13 > 37 pg/ml | OR = 1.050 | |||||||
| Ferraro, 2015 | L | CIS (110) | 35.0 | 2.0 | Converters (94) Non-converters (16) |
BL CSF levels in Converters (40m) | Higher than Non-converters | |
| Risk of conversion (40m): CXCL13 ≥ 15.4 pg/ml | HR = 2.900 | |||||||
| Risk of conversion (40m): CXCL13 ≥ 15.4 pg/ml ° | HR = NR | |||||||
| Brettschneider, 2010 | L | CIS (91) | 34.0 | 2.0 | Converters (45) Non-converters (46) |
BL CSF levels in Converters (24m) | Higher than Non-converters | |
| IgG index | Olesen, 2019 | L | ON (40) | 41.5 39.3 |
NR NR |
Converters (16) Non-converters (24) |
BL CSF levels in Converters (28.2m) | Higher than Non-converters |
| Likelihood of conversion (28.2m): IgG index > 0.64 | OR = 11.090 | |||||||
| Cinar, 2018 | L | CIS (41) | NR | NR | Converters (35) Non-converters (6) |
Risk of conversion (12.8m): IgG index > 0.7 | HR = 0.990 | |
| Time to conversion (12.8m): IgG index > 0.7 | Longer than IgG index < 0.7 | |||||||
| IgG oligoclonal bands (OCB) | Gaetani, 2020 | L | CIS (19) | 41.8 | 1.7 | Converters (12) Non-converters (7) |
Time to conversion (39.1m): OCB+ | Similar to OCB- |
| Kolcava, 2020 | L | CIS (64) | 36.5 | 2.0 | Converters (45) Non-converters (19) |
BL CSF levels in Converters (27m) | Higher than Non-converters | |
| Risk of conversion (27m): OCB+ | HR = 2.898 | |||||||
| Risk of conversion (27m): OCB+ ° | HR = 2.348 | |||||||
| Likelihood of conversion (27m): OCB+ | OR = 8.306 | |||||||
| Likelihood of conversion (27m): OCB+ ° | OR = 26.599 | |||||||
| Olesen, 2019 | L | ON (40) | 41.5 39.3 |
NR NR |
Converters (16) Non-converters (24) |
BL CSF levels in Converters (28.2m): | Higher than Non-converters | |
| Likelihood of conversion (28.2m): OCB+ | OR = 13.000 | |||||||
| Cinar, 2018 | L | CIS (41) | NR | NR | Converters (35) Non-converters (6) |
Time to conversion (12.8m): OCB+
(n = 26) |
Shorter than OCB- | |
| Risk of conversion (12.8m): OCB+
(n = 26) |
HR = 2.160 | |||||||
| Farina, 2017 | M | RRMS (90) | 42.5 | 1.5 | Converters (19) Non-converters (71) |
BL CSF levels in Converters (120m) | Higher than Non-converters | |
| Time to conversion (120m): OCB+ | Shorter than OCB- | |||||||
| Brettschneider, 2010 | L | CIS (91) | 34.0 | 2.0 | Converters (45) Non-converters (46) |
Truth table (24m): Converters vs. Non-converters | Sensitivity = 0.91 Specificity = 0.36 PPV = 0.59 NPV = 0.81 |
|
| Koch, 2007 | L | RRMS (78) | 34.0 | 2.0 | Converters (19) Non-converters (59) |
BL CSF levels in Converters (60M) | Similar to Non-converters | |
| Tumani, 1998 | L | ON (36) | 32.3 | NR | Converters (18) Non-converters (18) |
Truth table (48m): Converters vs. Non-converters | Sensitivity = 0.83 Specificity = 0.33 PPV = 0.56 NPV = 0.67 |
|
| OPN | De Fino, 2019 | L | CIS (24) | 37.4 | 1.3 | Converters (10) Non-converters (14) |
BL CSF levels in Converters (24m) | Similar to Non-converters |
| ROC (24m): Converters vs. Non-converters | AUC = 0.72 | |||||||
| Borras, 2016 | L | CIS (50) | 33.0 38.0 |
NR NR |
Converters (25) Non-converters (25) |
BL CSF levels in Converters (49.2m) | Similar to Non-converters | |
| Positive CSF$ | Thouvenot, 2019 | L | RIS (71) | 38.0 | NR | Converters (20) Non-converters (51) |
BL CSF levels in Converters (16m) | Higher than Non-converters |
| Risk of conversion (16m) (n = 70) |
HR = 2.900 | |||||||
| Risk of conversion (16m) ° (n = 65) |
HR = 1.220 | |||||||
| Cinar, 2018 | L | CIS (41) | NR | NR | Converters (35) Non-converters (6) |
BL CSF levels in Converters (12.8m) (n = 26) |
Higher than in Non-converters |
AUC, Area Under the Curve; BL, Baseline; CIS, Clinically Isolated Syndrome; Converters, ON/CIS/RIS subjects whom received MS diagnosis or RRMS subjects whom received SPMS diagnosis; CSF, Cerebrospinal fluid; H, High quality; HR, Hazard Ratio; L, Low quality; M, Moderate quality; MS, Multiple Sclerosis; NPV, Negative Predictive Value; Non-converters, stable ON/CIS/RIS/RRMS subjects; NR, Not reported; ON, Acute Optic Neuritis; OR, Odds Ratio; PPV, Positive Predictive Value; RIS, Radiologically Isolated Syndrome; ROC, Receiver Operator Characteristics; RRMS, Relapsing Remitting Multiple Sclerosis. Significant p-values are marked in bold. °Multivariate analyses; $ Defined as presence of OCB and/or IgG index > 0.7.