Autoantibodies to the HLA-B27 sequence cross-react with the hypothetical peptide from the arthritis-associated Shigella plasmid.
We previously reported elevated serum antibody levels to a peptide representing the HLA-B27 polymorphic region (B27 peptide) in HLA-B27(+) ankylosing spondylitis (AS) patients. A plasmid (pHS-2) isolated from arthritogenic Shigella flexneri strains had been shown to encode an amino acid sequence homologous to HLA-B27. Rabbit antibody to this sequence (pHS-2 peptide) strongly cross-reacted with B27 peptide and, to a much lesser extent, with Klebsiella nitrogenase peptide. Serum antibody levels to pHS-2 peptide were studied in 160 spondylarthropathy patients. 12 of 115 (10.4%) AS patients, 2 of 45 (4.4%) patients with Reiter's syndrome or reactive arthritis as well as 6 of 147 (4.1%) normal controls were shown to have elevated anti-pHS-2 peptide antibodies. Antibody levels to B27 and pHS-2 peptides were significantly correlated in 134 HLA-B27(+) patients (r = 0.333, P less than 0.001). 13 of 15 affinity-purified anti-B27 peptide antibodies from patients strongly cross-reacted with pHS-2 peptide, whereas only 3 weakly cross-reacted to nitrogenase peptide. Leucine appeared to be a critical residue for this cross-reaction. AS patients' anti-B27 peptide antibodies reacted with HLA-B27 transfected L cells. These results may suggest that pHS-2 peptide more efficiently "mimics" B27 peptide than does nitrogenase peptide. Involvement of pHS-2 in pathogenesis of spondylarthropathy through molecular mimicry mechanisms requires further study.
Department of Medicine, University of Florida, Gainesville 32610.
N
N
Tsuchiya
G
G
Husby
R C
RC
Williams
H
H
Stieglitz
P E
PE
Lipsky
R D
RD
Inman
D000595:Amino Acid Sequence; D000818:Animals; D001170:Arthritis, Infectious / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis* / Q000276:immunology; D003429:Cross Reactions; D005260:Female; D015796:HLA-B27 Antigen / Q000276:immunology*; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010957:Plasmids; D011817:Rabbits; D012763:Shigella flexneri / Q000235:genetics*; D013167:Spondylitis, Ankylosing / Q000209:etiology
D001323:Autoantibodies; D015796:HLA-B27 Antigen