I. Myelin: |
Reference |
MS/CIS |
Controls |
Serum |
CSF |
Antigen/technology |
Primary results |
Lisak et al. [63] |
41 |
5 ALS; 16 OND (GBS, SSPE);
22 HC |
IgG |
ND |
IMF of myelin in monkey or guinea pig spinal cord. |
All groups reacted with higher titers than HC. ALS showed greatest immunoreactivity. |
Panitch et al. [64] |
48 |
30 SSPE; 12 OND |
ND |
IgG |
MBP. Solid phase RIA. |
SSPE>MS>OND |
Gorny et al. [65] |
18 |
13 SSPE; 22 OND;
7 neurotic |
ND |
IgG |
MBP. RIA. |
SSPE (61%) > MS (44%) > OND (31%) |
Wajgt and Gorny, [66] |
40 |
40 neurotic |
ND |
IgG |
MBP, MAG. RIA. |
MS positive: MBP (35%), MAG (70%), both (33%). Neurotic (0%) |
Xiao et al. [67] |
30 |
30 OND; 30 HA |
ND |
IgG |
MOG. ELISA. |
MS (23%); OND (10%), HA (3%) |
Reindl et al. [68] |
130 |
32 OIND; 30 ONND; 10 RA |
IgG |
IgG |
MBP. MOG. WB, ELISA. |
No differences between groups by ELISA. WB highest in OIND; differences between groups not in favor of MS. |
Karni et al. [69] |
33 sera 31 CSF |
Sera: 31OND; 28 HC. CSF: 28 OND; 31 HC |
IgG, IgM, IgA |
IgG, IgM, IgA |
MBP, MOG. ELISA. |
CSF: Abs to MOG, MBP elevated in MS & OND vs. HC. Frequency higher to MOG in MS & OND (not to MBP). Sera: titers elevated in MS vs. ONDs & HC, but frequency similar between groups. |
Berger et al. [70] |
103 CIS OCB (+) |
None |
IgM |
ND |
MBP, MOG. WB. |
MOG/MBP: +/+ (21%); -/- (38%); +/- (41%). 95% of MOG/MBP +/+ had relapse & predicted RRMS (≈100%) |
Lampasona et al. [73] |
87 |
12 EC, 47 HC |
IgG, IgM |
ND |
MOG. WB, RBD. |
No difference between groups. |
Mantegazza et al. [74] |
262 (175 RR; 44 SP; 43 PP) |
131 OND 307 HC |
IgG |
IgG |
MOG (extracellular domain). ELISA. WB. |
CSF: no differences. Sera: MS (14%); OND (14%); HC (6%). Not specific for MS. CPMS: titer correlates with severity |
Lim et al. [78] |
47 CIS |
None |
IgG, IgM |
ND |
MBP. MOG. WB. |
Abs to MBP/MOG did not predict CDMS |
Lalive et al. [80] |
92 (35 RR; 33 SP;
24 PP). 36 CIS |
37 HC |
IgG |
ND |
MOG (native in transfected human cells) |
Significant differences between CIS, RR, SP vs. HC, but not PP. |
Rauer et al. [75] |
45 CIS |
56 HC |
IgM |
ND |
MBP, MOG. WB. |
No increase risk for CDMS. Ab (+) patients developed earlier relapses. |
Khalil et al. [77] |
28 |
20 HC |
IgG, IgM, IgA |
ND |
MOG. ELISA. |
IgM not significant. IgG and IgA significant. High degree of value overlaps between groups. |
Kuhle et al. [79] |
462 CIS |
None |
IgG, IgM |
ND |
MBP, MOG. WB. |
Risk of CDMS not influenced by any combination of positive Abs. |
Menge et al. [81] |
37 (17 RR;10 SP;
10 PP) |
13 HC |
IgG |
ND |
rhMOG ELISA |
No differences |
Greeve et al. [71] |
31 CIS |
None |
IgM |
ND |
MBP, MOG. WB. |
MOG/MBP: +/+ & +/- greater risk of CDMS than -/- |
Tomassini et al. [72] |
51 CIS |
None |
IgG, IgM |
ND |
MBP, MOG. WB. |
Any positive Ab predicted CDMS by Poser criteria, not McDonald criteria. |
Pittock et al. [82] |
72 (12 pI; 43 pII,
17 pIII) |
None |
IgG, IgM |
ND |
MOG ELISA. WB. |
No association with CDMS. |
Wang et al. [76] |
126 |
252 HC |
IgG, IgM |
ND |
MOG. EBNA. ELISA. |
2X increase of MS, but no association after adjustment for EBNA Abs. |
Belogurov et al. [83] |
26 |
22 OND, 11 HC |
IgG |
ND |
MBP. MOG. ELISA. |
MOG & MBP: Significant differences vs. HC, not OND. Only Abs to MBP 43-68, 146-170 distinguished MS from OND. |
Hedegaard et al. [84] |
17 |
17 HC |
IgG |
ND |
MBP microsphere. |
No differences. |
Chan et al. [85] |
25 patients prior to CIS |
21 HC |
IgG, IgM |
ND |
Linear MBP. Linear and native MOG. |
No association with CIS development. |
Tewarie, et al. [86] |
77 (37 RR; 27 SP,
13 PP) |
26 OND; 9 OIND |
IgG |
IgG |
Myelin |
No differences |
II. Non-myelin: |
Rawes et al. [88] |
20 |
17 OND, 13 HC |
IgG |
IgG |
Axolemma enriched fraction (AEF). ELISA |
Serum & CSF: significant differences in mean absorbance in MS compared to OND, HC. No correlation with myelin Ag |
Sadatipour et al. [89] |
70 (33 RR; 21 SP,
16 PP) |
41 OND, 38 HC |
Poly-valent Ig |
ND |
Gangliosides GM1, GM3, GD1a, GD1b, GD3 |
Significant differences in GM3: PP, SP compared to RRMS, OND, and HC |
Silber et al. [56] |
67 (39 RR;18 SP;
10 PP) |
40 OND; 21 OIND; 12 HC |
IgG |
IgG |
NF-L, NF-H, tubulin |
Anti-NF-L antibodies significantly elevated in PPMS and SPMS compared to controls; correlated with EDSS |
Eikelenblom et al. [57] |
51 MS: 21 RR;
20 SP; 10 PP |
None |
ND |
IgG |
NF-L, NF-H |
Anti-NF-L IgG index correlated with parenchymal fraction, T2 lesion load, T1 lesion load & ventricular fraction |
Lily et al. [94] |
58 (35 RR (9 benign); 23 SP |
12 HC 16 OND |
IgG, IgM |
ND |
SK-N-SH neurons Oligodendrocyte precursor cell lines |
Only SK-N-SH cells showed differential response between SP (75%) and RR (25%). No differences in OPCs. |
Mathey et al. [58] |
26 (13 RR;
4 possible, 9 CPMS) |
17 OIND 21 HC blood donors |
IgG |
ND |
Neurofascin NF186 (axonal) NF155 (oligodendrocyte) |
Highest titers: CPMS vs OIND to NF 155, which cross-reacts with NF 186. |
Lee et al. [7] |
37 (18 RR; 10 SP;
9 PP) |
8 HC, 5 AD |
IgG |
IgG |
hnRNP A1–M9 (AA 293-304) WB. |
Sera: MS (100% (+)); HC (0%); AD (0%). Single positive MS OCB in CSF. |
Srivastava et al. [59] |
397 |
329 OND; 59 HC |
IgG |
ND |
KIR4.1 ELISA |
KIR4.1 (AA 83-120): MS (47%); OND (0.9%), HC (0%). |
III. Myelin & non-myelin: |
Kanter et al. [128] |
16 (8 RR; 8 SP) |
11 OND |
ND |
IgG, IgM |
Lipid microarray |
MS vs OND: sulfatide. 3β-hydroxy-5α-cholestan-15-one, oxidized phosphatidylcholine, phosphatidyl ethanolmine, lysophosphatidyl ethanolamine, sphingo-myelin, lipopolysaccharide, asialo-GM-1. SPMS vs OND: GM1, asialo-GM1. |
Ousman et al.[54] |
12 RR |
12 OND |
ND |
IgG, IgM |
‘Myelin’ antigen array |
αB crystallin 21-40; golli-MBP iso J37; MBP; PLP, HSP, amyloid beta 1-12 |
Quintana et al. [130] |
14 RR vs 10 HC. 13 PP vs 12 HC. 37 RR vs 30 SP. |
See MS/CIS column (left) |
IgG, IgM |
ND |
Tripartite antigen array of CNS, HSP and lipid antigens |
RR vs HC: CNS & myelin Ags, GFAP, lactocerebroside, beta amyloid. PP vs HC: myelin Ags, beta amyloid, NF-68, superoxide dismutase. PP, SP vs. RR: lower titers to HSP. |
Derfuss et al. [55] |
sera: 56. CSF: 24 (16 CDMS, 8 probable MS) |
sera: 45 OIND;
12 OND;40 HCCSF: 25 OIND; 35 OND |
IgG |
IgG |
Contactin-2 (human)/TAG-1 (rat) |
Sera: no differences between groups. CSF: significance between MS & OIND but not OND. T-cells to TAG-1 with anti-MOG abs required to induce disease. |
AA: Aminoacid; Abs: Antibodies; Ag: Antigen; AD: Alzheimer ’s disease; ALS: Amyotrophic lateral sclerosis; CIS: Clinically isolated syndrome; CDMS: Clinically definite
multiple sclerosis; CNS: Central nervous system; CPMS: Chronic progressive multiple sclerosis; CSF: Cerebrospinal fluid; EBNA: Epstein Barr nuclear antigen; EC:
Encephalitis; ELISA: Enzyme-linked immunosorbent assay; GFAP: Glial fibrillary acidic protein; GBS: Guillain Barre Syndrome; HA: Headache; HC: Healthy controls;
hnRNP A1: Heterogeneous nuclear ribonuclear protein A1; HSP: Heat shock proteins; IMF: immunofluorescence; iso: isoform; MAG: Myelin associated glycoprotein; MBP:
Myelin basic protein; MOG: Myelin oligodendrocyte glycoprotein; MS: Multiple sclerosis; ND: Not done; NF-L: Neurofilament light chain; NF-H: Neurofilament heavy chain;
NF-68: Neurofilament 68; NF 155: Neurofascin 155 kDa; NF 186: Neurofascin 186 kDa; OCB: Oligoclonal bands; OIND: Other inflammatory neurologic disease; OND:
Other neurologic disease; ONND: Other non-inflammatory neurologic disease; p: pattern; PP: Primary progressive MS; RA: Rheumatoid arthritis; RBD: Radio-binding
assay; rh – recombinant, human; RIA: Radioimmunoassay; RRMS: Relapsing remitting multiple sclerosis; SP: Secondary progressive MS; SSPE: Subacute sclerosing
panencephalitis; TAG-1: Transiently expressed axonal glycoprotein 1; WB: Western blot