Autoantibodies to the HLA-B27 sequence cross-react with the hypothetical peptide from the arthritis-associated Shigella plasmid.

Abstract

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 < 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. (J.

“Natural” Human Leukocyte Antigen Antibodies Found in Nonalloimmunized Healthy Males

“…Subsequently, many studies have extended the concept of cross reactivity with HLA and various other peptide fragments. As stated in the introduction, many publications now show cross reactivity of HLA with microbial antigens (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15).…”

“…The crystal structure of staphylococcal enterotoxin that forms a complex with class II molecules has been identified (10). There have been reports of HLA B27 cross reactivity with Klebsiella pneumoniae (11,12), with Shigella (13,14), and with Yersinia (15). Cross-reactions measured by inhibition of the cytotoxicity reaction is to some extent unreliable, since complement inhibition is also involved.…”

Antibodies to HLA-E in Nonalloimmunized Males: Pattern of HLA-Ia Reactivity of Anti–HLA-E–Positive Sera

“…A pattern in the allelic specificity of the natural Abs is observed (12). The allelic specificities in healthy males are attributed to the exogenous Ags of microbes or pathogens (13)(14)(15)(16)(17)(18)(19)(20)(21)(22) or to dietary meat proteins (12). Ag mimicry of several bacterial, fungal, or viral peptide sequences with HLA-Ia alleles (23) may explain single or a few allelic reactivities but not the entire pattern of the allelic specificities of the natural allo-HLA Abs.…”

MICA allele typing of HLA-B27 positive japanese patients with seronegative spondylarthropathies and healthy individuals: Differential linkage disequilibrium with HLA-B27 subtypes

“…A number of possibilities, including presentation of "arthritogenic" peptides by HLA-B27 ( 5 ) and molecular mimicry between HLA-B27 sequences and microorganisms (6), have been proposed. However, such hypotheses do not readily account for the tissue specificity of SPA, because HLA-B27 is expressed on most nucleated cells.…”