Molecular mimicry in the pathogenesis of spondyloarthropathies. A critical appraisal of cross-reactivity between microbial antigens and HLA-B27.
We describe an amino acid homology between a virulence plasmid encoded outer membrane protein of Yersinia, YadA (previously called Yop1) and HLA-B27. This tetrapeptide is also included in the hexapeptide, earlier found to be identical between Klebsiella nitrogenase and HLA-B27. The synthetic peptide based on the HLA-B27 homologous portion of the YadA does not stimulate lymphocytes obtained from HLA-B27+ patients with Yersinia-triggered reactive arthritis or from controls. One-third of the yersiniosis patients have antibodies against the synthetic peptide. Instead of recognizing the HLA-B27 homologous portion, the antibodies are directed against the left flanking sequence of the synthetic peptide. Similar results were obtained regarding antibody response to Klebsiella nitrogenase derived synthetic peptide included in the panel of controls; the response was not restricted to patients with reactive arthritis nor was it specifically directed against the sequence shared by HLA-B27 and Klebsiella pneumoniae nitrogenase. The present results do not support the role of molecular mimicry or cross-reactive antibodies in the pathogenesis of spondyloarthropathies.
Lahesmaa
R
R
Department of Medical Microbiology, Turku University, Finland.
Skurnik
M
M
Granfors
K
K
Möttönen
T
T
Saario
R
R
Toivanen
A
A
Toivanen
P
P
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000917:Antibody Formation; D000942:Antigens, Bacterial / Q000276:immunology*; D016918:Arthritis, Reactive / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D003429:Cross Reactions; D005260:Female; D005802:Genes, MHC Class II; D015796:HLA-B27 Antigen / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012689:Sequence Homology, Nucleic Acid; D013167:Spondylitis, Ankylosing / Q000209:etiology* / Q000276:immunology; D015007:Yersinia; D015009:Yersinia Infections / Q000276:immunology
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D015796:HLA-B27 Antigen