A study of molecular mimicry and immunological cross-reactivity between hepatitis B surface antigen and myelin mimics.
On the basis of the reported association between hepatitis B vaccination (HBvacc) and autoimmune demyelinating complications such as multiple sclerosis (MS), we have looked for aminoacid similarities between the small hepatitis B virus surface antigen (SHBsAg), and the MS-autoantigens myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) that could serve as targets of immunological cross-reactivity. Twenty-mer peptides spanning 4 SHBsAg/MOG and 1 SHBsAg/MBP mimicking pairs, were constructed and tested by ELISA as targets of cross-reactive responses. A total of 147 samples from 58 adults were collected before HBvacc (58/58), and post-HBvacc (48/58 before the second and 41/58 before the third boost). Eighty-seven sera from anti-SHBsAg antibody negative patients with various diseases were tested as pathological controls. Reactivity to at least one of the SHBsAg peptides was found in 8 (14%) pre-HBvacc subjects; amongst the remaining 50, reactivity to at least one of the SHBsAg peptides appeared in 47 (94%) post-HBvacc. Reactivity to at least one of the MOG mimics was present in 4 (8%) pre-HBvacc and in 30 (60%) post-HBvacc (p < 0.001). Overall 30/50 (60%) vaccinees had SHBsAg/MOG double reactivity on at least one occasion compared to none before-vaccination and in 2 (2%) of the pathological controls (p < 0.001 for both). SHBsAg/MOG double reactivity was cross-reactive as confirmed by inhibition studies. At 6 months post-vaccination, 3 of the 4 anti-MOG reactive cases before vaccination and 7 of the 24 (29%) of the anti-MOG reactive cases at 3 months post-vaccination had lost their reactivity to MOG5-24. There was no reactivity to the SHBsAg/MBP mimics. None of the vaccinees reported symptoms of demyelinating disorders. In view of the observed SHBsAg/MOG cross-reactivity, the vaccine's possible role as an immunomodulator of viral/self cross-reactivity must be further investigated.
Bogdanos
Dimitrios-Petrou
DP
Institute of Liver Studies, London School Medicine at King's College Hospital, UK.
Smith
Heather
H
Ma
Yun
Y
Baum
Harold
H
Mieli-Vergani
Giorgina
G
Vergani
Diego
D
D000328:Adult; D000595:Amino Acid Sequence; D003429:Cross Reactions; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D017386:Sequence Homology, Amino Acid
D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; C571326:MOG protein, human; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein