Background
Methods
Study design
Sex: F/M | 70/30 |
---|---|
Age, years: mean ± SD | 37.3 ± 10.6 |
Disease duration, months: mean ± SD | 30.5 ± 46.6 |
Disease severity, EDSS: mean ± SD | 2.0 ± 1.3 |
CA MS: n/total (%) | 77/100 (77%) |
CS MS: n/total (%) | 23/100 (23%) |
Gd+ MS: n/total (%) | 37/100 (37%) |
Gd- MS: n/total (%) | 63/100 (63%) |
Blood-CSF-barrier dysfunction, QAlb: positive/total (%) | 18/100 (18%) |
Intrathecal IgG synthesis, IgG Index: positive/total (%) | 71/100 (71%) |
CSF-restricted oligoclonal IgG bands: positive/total (%) | 84/100 (84%) |
Patients | n | Sex | Age (years) | Type of disease | |
---|---|---|---|---|---|
F | M | ||||
OIND | 100 | 70 | 30 | 37.5 ± 10.7 | |
29 | Chronic inflammatory demyelinating polyneuropathy | ||||
18 | Viral encephalomyelitis | ||||
18 | Acute inflammatory demyelinating polyneuropathy | ||||
11 | Bacterial meningitis | ||||
10 | Optic neuritis | ||||
6 | HIV encephalopathy | ||||
3 | Neurolupus | ||||
3 | NeuroSjogren | ||||
3 | NeuroBechet | ||||
NIND | 100 | 70 | 30 | 38.1 ± 11.1 | |
14 | Transient ischemic attack | ||||
13 | Epilepsy | ||||
12 | Headache | ||||
10 | Cervical spondylosis | ||||
10 | Hereditary ataxia | ||||
9 | Vascular dementia | ||||
9 | Migraine | ||||
8 | Amyotrophic lateral sclerosis | ||||
7 | Compression neuropathy | ||||
4 | Paresthesias | ||||
4 | Alzheimer disease |
Cerebrospinal fluid and serum sampling
Magnetic resonance imaging analysis
Serum and cerebrospinal fluid levels and intrathecal synthesis of anti-Epstein-Barr virus antibodies
Calculation of Epstein-Barr nuclear antigen and anti-viral capsid antigen IgG -specific antibody index
Antigen-specific immunoblotting
Determination of affinity distributions of Epstein-Barr virus-specific antibodies
Determination of Epstein-Barr virus-specific IgG oligoclonal band affinity
Statistics
Results
Cerebrospinal fluid and serum levels and intrathecal synthesis of anti-Epstein Barr virus IgG in relapsing-remitting multiple sclerosis patients and controls
Anti-EBNA-1 IgG | Anti-VCA IgG | |||
---|---|---|---|---|
CSF | Serum | CSF | Serum | |
RRMS (n = 100) | 96/100 (96%)a
| 99/100 (99%) | 65/100 (65%) | 90/100 (90%) |
OIND (n = 100) | 91/100 (91%) | 96/100 (96%) | 86/100 (86%)b
| 94/100 (94%) |
NIND (n = 100) | 86/100 (86%) | 94/100 (94%) | 74/100 (74%) | 90/100 (90%) |
Anti-EBNA-1 IgG | Anti-VCA IgG | |||||
---|---|---|---|---|---|---|
CSF levels (AU) | Serum levels (AU) | AI >1.5 | CSF levels (AU) | Serum levels (AU) | AI >1.5 | |
Median; IQR | Median; IQR | n/total (%) | Median; IQR | Median; IQR | n/total (%) | |
Total RRMS (n = 100) | 79.4; 37.5 to 174.3a
| 52,056; 23,274 to 94,815c, d
| 6/100 (6%) | 36.4; 0.0 to 74.2 | 18962; 10659 to 46669 | 2/100 (2%) |
CA RRMS (n = 77) | 74.8; 38.2 to 167.7 | 41,783; 21,479 to 83,254 | 4/77 (5.2%) | 41.9; 0.0 to 83.1 | 22546; 12433 to 51763 | 0/77 (0%) |
CS RRMS (n = 23) | 100.4; 51.0 to 272.7 | 59833; 36072 to 261044 | 2/23 (8.7%) | 21.1; 0.0 to 59.9 | 14240; 6632 to 32515 | 2/23 (8.7%) |
Gd + RRMS (n = 37) | 90.4; 36.7 to 238.7 | 39325; 21479 to 105629 | 3/37 (8.1%) | 23.7; 0.0 to 60.9 | 16836; 12476 to 37484 | 0/37 (0%) |
Gd- RRMS (n = 63) | 79.4; 43.3 to 139.0 | 53092; 27500 to 84551 | 3/63 (4.8%) | 38.9; 0.0 to 85.1 | 21335; 10036 to 47672 | 2/63 (3.4%) |
OIND (n = 100) | 73.1; 31.0 to 151.6b
| 23503; 10386 to 44089 | 6/100 (6%) | 82.7; 30.3 to 294.1e, f
| 29938; 8846 to 65475 | 5/100 (5%) |
NIND (n = 100) | 49.7; 15.9 to 118.9 | 24383; 7252 to 54754 | 2/100 (2%) | 39.1; 0.0 to 130.8 | 28056; 12281 to 53124 | 1/100 (1%) |
EDSS | Disease duration (months) | |
---|---|---|
CSF anti-EBNA-1 IgG levels (AU) | r = -0.1642 | r = 0.1181 |
CSF anti-VCA IgG levels (AU) | r = 0.2294 | r = 0.1184 |
Serum anti-EBNA-1 IgG levels (AU) | r = -0.336* | r = 0.0963 |
Serum anti-VCA IgG levels (AU) | r = 0.1901 | r = 0.1443 |
Epstein Barr virus-specific IgG oligoclonal bands in relapsing-remitting multiple sclerosis patients
ASI positive RRMS | ASI negative RRMS | |
---|---|---|
(n = 24) | (n = 76) | |
Sex: F/M | 17/7 | 53/23 |
Age, years: mean ± SD | 36.7 ±9.1 | 37.5 ±11.1 |
Disease duration, months: mean ± SD | 28.7 ±40.2 | 30.8 ±48.5 |
Disease severity, EDSS: mean ± SD | 2.2 ±1.5 | 2.0 ±1.2 |
CA MS: n/total (%) | 20/24 (83.3%) | 57/76 (75.0%) |
CA MS: n/total (%) | 4/24 (16.7%) | 19/76 (25.0%) |
Gd+ MS: n/total (%) | 13/24 (54.2%) | 24/76 (31.6%) |
Gd- MS: n/total (%) | 11/24 (45.8%) | 52/76 (68.4%) |
CSF anti-EBNA-1 IgG (AU): mean ± SD | 193.0 ±266.0 | 155.2 ±232.1 |
CSF anti-VCA IgG (AU): mean ± SD | 41.6 ±56.9 | 81.5 ±243.4 |
Serum anti-EBNA-1 IgG (AU): mean ± SD | 126502 ±205623 | 132114 ±198699 |
Serum anti-VCA IgG (AU): mean ± SD | 21572 ±24497 | 50122 ±75151a
|
EBNA-1 AI >1.5: n/total (%) | 3/21 (12.5%) | 3/76 (4.0%) |
VCA AI >1.5: n/total (%) | 1/21 (4.2%) | 1/76 (1.3%) |
Affinity distributions of anti-Epstein Barr nuclear antigen and anti-viral capsid antigen IgG in relapsing-remitting multiple sclerosis patients and controls
RRMS | OIND | NIND | |
---|---|---|---|
(n = 50) | (n = 50) | (n = 50) | |
CSF anti-EBNA-1 IgG: RA4 >2.5, n/total (%) | 48/50 (96%)a
| 45/50 (90%) | 40/50 (80%) |
CSF anti-VCA IgG: RA4 >2.5, n/total (%) | 48/50 (96%)b
| 47/50 (94%)c
| 40/50 (80%) |
Serum anti-EBNA-1 IgG: RA4 >2.5, n/total (%) | 47/50 (94%) | 47/50 (94%) | 48/50 (96%) |
Serum anti-VCA IgG: RA4 >2.5, n/total (%) | 44/50 (88%)d
| 40/50 (80%) | 32/50 (64%) |