Introduction
Methods
Study participant inclusion and exclusion criteria
Clinical management, data, and sample acquisition
Sample acquisition
Genotyping
Proteomic analysis
Statistical analysis
Variable | TBI cohort (matched samples) n = 90 | Control cohort n = 15 | TBI validation cohort (non-matched samples) n = 96 | Unit/metric |
---|---|---|---|---|
Age | 57 (41–62) | 25 (22–29) | 54 (36.5–63) | Years |
Male | 67 (74) | 7 (47) | 72 (75) | count (%) |
GCS admission | 7 (3–9) | 6 (3–11) | Scale 1–15 | |
GCS motor admission | 4 (1–5) | 4 (1–5) | Scale 1–6 | |
Pupils | Bilaterally responsive: 67 (74) | Bilaterally responsive: 69 (72) | Count (%) | |
Unilaterally unresponsive: 11 (12) | Unilaterally unresponsive: 9 (9.4) | |||
Bilaterally unresponsive: 9 (10) | Bilaterally unresponsive: 16 (17) | |||
Missing: 3 (3.3) | Missing: 2 (2.1) | |||
Head AIS | 1 (minor): 0 (0) | 1 (minor): 0 (0) | Score 1–6 | |
2 (moderate): 0 (0) | 2 (moderate): 1 (1.0) | |||
3 (serious): 10 (11) | 3 (serious): 10 (10.4) | |||
4 (severe): 30 (33) | 4 (severe): 25 (26) | |||
5 (critical): 43 (48) | 5 (critical): 57 (59) | |||
6 (maximum): 0 (0) | 6 (maximum): 0 (0) | |||
Missing: 7 (7.8) | Missing: 3 (3.1) | |||
ISS | 25 (19–29) | 25 (17–29) | Scale | |
Missing: 7 (7.78) | Missing: 3 (3.1) | |||
Multitrauma | 29 (32) | 26 (27) | Count (%) | |
Hypotension at SoA | 2 (2.2) | 1 (1.0) | Count (%) | |
Missing: 24 (27) | Missing: 26 (27) | |||
Hypoxia at SoA | 15 (17) | 18 (19) | Count (%) | |
Missing: 4 (4.4) | Missing: 4 (4.2) | |||
Stockholm CT score | 2.5 (2–3.3) | 2.5 (1.9–3.3) | Scale | |
QA | 0.0041 (0.0018–0.011) | 0.0040 (0.0035–0.0060) | 0.009 (0.003–0.027) | Quotient |
Missing: 19 (21.1) | Missing: 71 (74) | |||
APOE allele status | No allele: 57 (63) | No allele: 64 (67) | Count (%) | |
Heterozygote: 16 (18) | Heterozygote: 17 (18) | |||
Homozygote: 2 (2) | Homozygote: 3 (3.1) | |||
Missing: 15 (17) | Missing: 12 (12.5) | |||
Evacuation aSDH | 33 (38) | 50 (61) | ||
Evacuation EDH | 6 (6.8) | 14 (17) | ||
Evacuation tICH | 24 (27) | 13 (16) | ||
ICP monitora | 38 (43) | 60 (73) | ||
Other intracranial monitorationb | 55 (63) | 39 (48) | ||
GOS | GOS 1 (death): 12 (13) | GOS 1 (death): 10 (10.4) | Score 1–5 | |
GOS 2 (vegetative): 0 (0) | GOS 2 (vegetative): 1 (1.0) | |||
GOS 3 (severe disability): 34 (38) | GOS 3 (severe disability): 30 (31) | |||
GOS 4 (moderate disability): 28 (31) | GOS 4 (moderate disability): 29 (30) | |||
GOS 5 (good recovery): 16 (18) | GOS 5 (good recovery): 26 (27) | |||
Unfavorable GOS | GOS 1–3: 46 (51) | GOS 1–2: 41 (43) | count (%) |
Protein characterization
Parallel assessments in CSF, serum, and relationship with BBB disruption
Pathway and outcome analysis
Results
Patient demographics
Protein characterization
TBI alters CSF and serum protein levels and upregulates neuroinflammatory pathways
BBB disruption yields a protein signature in CSF and is predictive of outcome
Protein, antibody | Specific function | Protein size [kDa] | τ | adjusted p value |
---|---|---|---|---|
C1QB HPA052116 | Innate immunity/complement system | 26.7 | 0.67 | < 0.001 |
CFB HPA001817 | Innate immunity/complement system | 85.5 | 0.66 | < 0.001 |
C9 HPA029577 | Innate immunity/complement system | 63.2 | 0.65 | < 0.001 |
C9 HPA070709 | Innate immunity/complement system | 63.2 | 0.65 | < 0.001 |
C1QA HPA002350 | Innate immunity/complement system | 26 | 0.64 | < 0.001 |
MASP2 HPA029314 | Innate immunity/complement system | 75.7 | 0.58 | < 0.001 |
VCAM1 HPA069867 | Cell cell communication | 81.3 | 0.54 | < 0.001 |
FCN3 HPA071173 | Innate immunity/complement system | 31.7–32.9a | 0.54 | < 0.001 |
MASP2 HPA029313 | Innate immunity/complement system | 75.7 | 0.52 | < 0.001 |
C5 HPA075945 | Innate immunity/complement system | 188.3 | 0.52 | < 0.001 |
Proteins associated with BBB disruption are outcome predictors following TBI
Protein, antibody | Compartment | Highest tissue enrichment | Protein size [kDa] | Coefficient | ΔR2 | adjusted p value | QA subgroup analysis |
---|---|---|---|---|---|---|---|
STMN4 HPA078407 | CSF | cns | 19.4–30.4a | − 0.00505 | 0.121 | 0.04548 | No |
C5 HPA075945 | CSF | Liver/gallbladder | 188.3 | − 0.00095 | 0.106 | 0.04548 | No |
GPR26 HPA062736 | CSF | cns | 37.6 | − 0.00684 | 0.099 | 0.04548 | No |
CFB HPA001817 | Serum | Liver/gallbladder | 85.5 | 0.00098 | 0.092 | 0.04548 | Yes |
FCN1 HPA001295 | Serum | Blood | 35.1 | 0.00303 | 0.082 | 0.04548 | Yes |
C9 HPA070709 | CSF | Liver/gallbladder | 63.2 | − 0.00123 | 0.074 | 0.04548 | Yes |
IL6 HPA064428 | Serum | Adipose/soft tissue | 13.9–23.7a | 0.00185 | 0.071 | 0.04548 | Yes |