Cross-reactivity between related sequences found in Acinetobacter sp., Pseudomonas aeruginosa, myelin basic protein and myelin oligodendrocyte glycoprotein in multiple sclerosis.
To investigate the possible role of molecular mimicry to bacterial components in multiple sclerosis (MS) pathogenesis we examined antibody responses to mimicry peptide sequences of Acinetobacter, Pseudomonas aeruginosa and myelin components. Antibodies to mimicry peptides from Acinetobacter (p<0.001), P. aeruginosa (p<0.001), myelin basic protein (MBP) (p<0.001) and myelin oligodendrocyte glycoprotein (MOG) (p<0.001) were significantly elevated in MS patients compared to controls. Antisera against MBP (residues 110-124) reacted with both Acinetobacter and Pseudomonas peptides from 4- and gamma-carboxymuconolactone decarboxylase, respectively. MOG (residues 43-57) antisera reacted with Acinetobacter peptide from 3-oxo-adipate-CoA-transferase subunit A. The role of these bacteria in MS is unclear but demonstrates that molecular mimicry is not restricted to viruses suggesting bacterial infections could play a role in MS pathogenesis. Further work is required to evaluate the relevance of these cross-reactive antibodies to the neuropathology of MS.
Division of Infection, Immunity and Inflammatory Diseases, King's College London, Waterloo Campus, London, SE1 9NN, UK.
L E
LE
Hughes
P A
PA
Smith
S
S
Bonell
R S
RS
Natt
C
C
Wilson
T
T
Rashid
S
S
Amor
E J
EJ
Thompson
J
J
Croker
A
A
Ebringer
D000150:Acinetobacter / Q000201:enzymology / Q000276:immunology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism*; D002262:Carboxy-Lyases / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D015256:Coenzyme A-Transferases / Q000276:immunology / Q000378:metabolism; D003429:Cross Reactions; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000382:microbiology; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000378:metabolism; D008297:Male; D051379:Mice; D038602:Mice, Biozzi; D008875:Middle Aged; D018716:Molecular Mimicry / Q000276:immunology; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology* / Q000382:microbiology; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000201:enzymology / Q000276:immunology*; D017386:Sequence Homology, Amino Acid
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007106:Immune Sera; C571326:MOG protein, human; C571327:Mog protein, mouse; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D015256:Coenzyme A-Transferases; C028573:3-oxoadipate CoA-transferase; D002262:Carboxy-Lyases; C019832:4-carboxymuconolactone decarboxylase