Table 3B.
Overview inflammatory biomarkers associated with longitudinal clinical measures in MS publications.
| Biomarker | Study | Quality | Cohort (n) | Age (y) | EDSS | Associated clinical outcome measure (follow-up time): statistical analysis | Result statistical analysis |
|---|---|---|---|---|---|---|---|
| κ-FLC | Voortman, 2017 | L | CIS+RRMS (61) | 28.8 | 2.0 | δEDSS (57.6m) | R = NR |
| Makshakov, 2015 | L | Converters (98) | 32.0 | NR | EDSS (24m) | R = 0.418 | |
| κ-FLC / Λ -FLC ratio | Rathbone, 2018 | L | CIS (43) RRMS (50) |
45.0 40.5 |
NR NR |
EDSS (60m) (n = 29) |
R = -0.370 |
| Voortman, 2017 | L | CIS+RRMS (61) | 28.8 | 2.0 | δEDSS (57.6my) | R = NR | |
| Adiponectin (Adp) | Signoriello, 2021 | M | MS (66) | 43.9 | 2.0 | EDSS (55.2m): Adp > 9.91 μg/ml | Higher than Adp < 9.91 |
| EDSS increase (55.2m): Adp > 9.91 μg/ml ° | OR = 0.62 | ||||||
| MSSS (55.2m): Adp > 9.91 μg/ml | Higher than Adp < 9.91 | ||||||
| MSSS increase (55.2m): Adp > 9.91 μg/ml ° | OR = 1.72* | ||||||
| PI (55.2m): Adp > 9.91 μg/ml | Higher than Adp < 9.91 | ||||||
| AF | Decker, 2016 | M | MS (30) | 31.2 | NR | Annual δEDSS (>12m) | R = 0.810 |
| BDNF | Sarchielli, 2002 | L | SPMS (15) | 38.4 | 3.7 | EDSS increase (24m) (n = 8) |
Lower BDNF values |
| CCL3 | Puthenparempil, 2020 | L | RRMS (30) | 35.7 | NR | Disease reactivation$(36.4m): CCL3 > 0.736 pg/mL | OR = 4.9 |
| YKL-40 (CHI3L1) | Gil-Perotin, 2018 | M | RRMS (25) | 35.0 | 2.0 | EDSS increase: predictor * | β = 1.097 |
| HR = 2.996 | |||||||
| Comabella, 2010 | L | Converters (48) | 26.8 | NR | EDSS (12m) (n = 44) |
R = 0.340 | |
| EDSS (24m) (n = 39) |
R = 0.400 | ||||||
| EDSS (36m) (n = 41) |
R = 0.470 | ||||||
| EDSS (48m) (n = 37) |
R = 0.380 | ||||||
| EDSS (60m) (n = 29) |
R = 0.290 | ||||||
| CXCL8 (IL-8) | Stampanoni-Bassi, 2018 | L | RRMS (150) | NR | NR | EDSS (12m) | R = NR |
| EDSS (36m) | R = 0.242 | ||||||
| PI (36m) | R = 0.246 | ||||||
| CXCL12 | Farina, 2017 | M | MS (90) | 42.5 | 1.5 | EDSS (120m post onset) (n = 21) |
R = 0.679 |
| GFAP | Norgren, 2004 | M | RRMS (58) SPMS (21) PPMS (15) PRMS (5) |
34 42 44 31 |
1.5 3.5 3 6 |
EDSS (48m) (RR + SP + PP + PR) |
R = 0.210 |
| PI (48m) (RR + SP + PP + PR) |
R = 0.240 | ||||||
| GM-CSF | Farina, 2017 | M | MS (90) | 42.5 | 1.5 | EDSS (120m post onset) (n = 21) |
R = 0.626 |
| IgG oligoclonal bands (OCB) | Giedraitiene, 2021 | M | RRMS (49) | 47.3 | 2.8 | EDSS (60m): OCB+ | Similar to OCB- |
| δSDMT(60m) = -3.1 – 1.0x(δRNFL_T) + 3.3xOCB | R² = 0.599 | ||||||
| δSDMT(60m) = -8.8 – 1.1x(δRNFL_PMB) + 4.4xOCB | R² = 0.480 | ||||||
| Karrenbauer, 2021 | L | MS OCB+ (6494) MS OCB- (828) |
38.1 40.8 |
NR NR |
Reach EDSS 3.0 (NR): OCB+ | Similar to OCB- | |
| Risk EDSS 3.0 (NR): OCB+
(n = 5055) |
HR = 1.29 | ||||||
| Reach EDSS 4.0 (NR): OCB+ | Similar to OCB- | ||||||
| Risk EDSS 4.0 (NR): OCB+
(n = 5802) |
HR = 1.38 | ||||||
| Reach EDSS 6.0 (NR): OCB+ | Similar to OCB- | ||||||
| Risk EDSS 6.0 (NR): OCB+
(n = 6398) |
HR = 1.20 | ||||||
| Oechtering, 2021 | L | MS+CIS (530) | 35.7 | NR | MSSS (61.2m): OCB+ vs. OCB- (n = 529) | β = 0.860 | |
| MSSS (61.2m): OCB+IgG-IgM- (n = 114) vs. OCB-IgG-IgM- (n = 46) | β = 0.940 | ||||||
| MSSS (61.2m): OCB+IgG-IgM- vs. OCB-IgG-IgM- ° | β = 0.730 | ||||||
| MSSS (61.2m): OCB+IgG+IgM- (n = 228) vs. OCB-IgG-IgM- | β = 0.730 | ||||||
| MSSS (61.2m): OCB+IgG+IgM- vs. OCB-IgG-IgM- ° | β = 0.860 | ||||||
| MSSS (61.2m): OCB+IgG+IgM+ (n = 111) vs. OCB-IgG-IgM- | β = 1.030 | ||||||
| MSSS (61.2m): OCB+IgG+IgM+ vs. OCB-IgG-IgM- ° | β = 1.110 | ||||||
| Farina, 2017 | M | MS (90) | 42.5 | 1.5 | EDSS (120m post onset): OCB+
(n = 21) |
Higher than OCB- | |
| BRB (120m post onset): OCB+ test failed (n = 21) |
Higher than OCB- | ||||||
| Koch, 2007 | L | MS (143) | 39.0 | 3.0 | EDSS increase vs. stable (60m) | Similar OCB+ / OCB- ratio | |
| Similar OCB count | |||||||
| PPMS (50) | 45.5 | 4.0 | EDSS increase vs. stable (60m) | Similar OCB+ / OCB- ratio | |||
| Similar OCB count | |||||||
| IgM oligoclonal bands (OCMB) | Capuano, 2021 | M | RRMS (78) | 32.9 | 2.0 | Reach EDSS > 3.0 (115.2m) (n = 20) |
HR = 4.39 |
| Reach EDSS > 3.0 (115.2m)° (n = 20) |
HR = 2.93 | ||||||
| Reach EDSS > 4.0 (115.2m) (n = 8) |
HR = 5.39 | ||||||
| IL-1β | Farina, 2017 | M | MS (90) | 42.5 | 1.5 | EDSS (120m post onset) (n = 21) |
R = 0.625 |
| Rossi, 2014 | L | RRMS (170) | 36.3 | 2.2 | EDSS (60m): IL-1β+ | Higher than IL-1β- | |
| EDSS increase (60m): %RRMS IL-1β+ | Higher than IL-1β- | ||||||
| Reach EDSS 3.0 (60m): IL-1β+ | OR = 4.34 | ||||||
| Reach EDSS > 3.0 (60m): IL-1β+ | OR = 3.38 | ||||||
| Reach EDSS 4.0 (60m): IL-1β+ | OR = 4.12 | ||||||
| Reach EDSS > 4.0 (60m): IL-1β+ | OR = 3.32 | ||||||
| MSSS (60m): IL-1β+ | Higher than IL-1β- | ||||||
| MSFC worsening (60m): %RRMS IL-1β+ | Higher than IL-1β- | ||||||
| Disability progression based on MSFC (60M): IL-1β+ | OR = 2.13 | ||||||
| MSFC worsening (60M): IL-1β+ | OR = 2.21 | ||||||
| PI increase (60m): IL-1β+ | Higher than IL-1β- | ||||||
| BREMS (60m): IL-1β+ | OR = 26.61 | ||||||
| Rossi, 2014 | L | RRMS (170) | 36.3 | 2.2 | MSSS (48m): IL-1β+ | Higher than IL-1β- | |
| PI (48m): IL-1β+ | Higher than IL-1β- | ||||||
| IL-6 | Stampanoni-Bassi, 2018 | L | RRMS (150) | NR | NR | EDSS (12m) | R = NR |
| EDSS (24m) | R = 0.194 | ||||||
| EDSS (36m) | R = 0.274 | ||||||
| PI (36m) | R = 0.311 | ||||||
| IL-9 | Ruocco, 2015 | M | RRMS High-IL9 (50) RRMS Low IL9 (57) |
32.2 31.8 |
1.3 2.0 |
EDSS (48m): IL-9 > 100 pg/ml | Lower than IL-9 < 100 |
| Reach EDSS 4.0 (48m): IL-9 > 100 pg/ml | OR = 0.24 | ||||||
| MSSS (48m): IL-9 > 100 pg/ml | Lower than IL-9 < 100 | ||||||
| PI (48m): IL-9 > 100 pg/ml | Lower than IL-9 < 100 | ||||||
| IL-17 | Ruocco, 2015 | M | RRMS Low IL9 (57) | 31.8 | 2.0 | Increased PI (48m): IL-17+ | Higher than IL17- |
| miR-142-3p | Mandolesi, 2017 | L | Active RRMS (18) Nonactive RRMS (12) |
32.1 43.2 |
1.8 1.7 |
PI (24-60m) (n = 21) |
R = 0.500 |
| Quotient κ-FLC | Makshakov, 2015 | L | Converters (98) | 32.0 | NR | EDSS (24m) | R = 0.410 |
| TNF-α | Sharief, 1991 | L | PMS (17) | 37.4 | 3.7 | EDSS (24m) | R = 0.873 |
| PI (24m) | R = 0.851 |
β, regression coefficient; BREMS, Bayesian Risk Estimate for Multiple Sclerosis; CIS, Clinically Isolated Syndrome; Converters, CIS patients whom received a MS diagnosis; EDSS, Expanded Disability Status Scale; H, High quality; HR, Hazard ratio; L, Low quality; m, months; M, Moderate quality; MS, Multiple Sclerosis; MSFC, Multiple Sclerosis Functional Composite; MSSS, Multiple Sclerosis Severity Score; NR, Not reported; OR, Odds ratio; PI, Progression Index; P(MS), Progressive Multiple Sclerosis; PP(MS), Primary Progressive Multiple Sclerosis; PR(MS), Progressive Relapsing Multiple Sclerosis; RNFL_PMB, Papillomacular bundle retinal nerve fibre layer thickness; R, Spearman or Pearson correlation coefficient; RNFL_T, Temporal segment retinal nerve fiber layer thickness; RR(MS), Relapsing-Remitting Multiple Sclerosis; SDMT, Symbol Digit Modalities Test; SP(MS), Secondary Progressive Multiple Sclerosis. Significant p-values are marked in bold; *Multivariable analyses; °Multivariate analyses; $ Not specified whether clinical or radiological disease reactivation.