Ankylosing spondylitis and reactive arthritis are seronegative spondyl
oarthropathies, which are strongly associated with HLA-B27. Despite in
tensive investigation, the basis for this association is not clear. Ho
wever, in recent years one favored hypothesis to explain this linkage
has been that of molecular mimicry, i.e., sharing of linear or conform
ational epitopes common to microbial antigens and host structures. Dur
ing the past few years several examples of molecular mimicry between H
LA-B27 and microbial antigens have been described. Heat shock proteins
, among others, have been considered as target candidates for autoimmu
ne phenomena, because of the high degree of homology between bacterial
and mammalian species. Reactive arthritis triggered by Yersinia or Sa
lmonella provides a unique model for studying the pathogenetic mechani
sms underlying human inflammatory joint diseases in general, because t
he arthritogenic microbes are known and well-characterized. We have de
scribed two bacterial proteins that share amino acid homology with HLA
-B27, namely YadA (Yersinia adhesin) and OmpH, outer surface proteins
of Yersinia and Salmonella, respectively. Notably, the area of identit
y of these amino acid sequences is located in the same place on the HL
A-B27 molecule as a hexapeptide identical between Klebsiella nitrogena
se and HLA-B27, and a pentapeptide shared by a Shigella flexneri prote
in and HLA-B27. We have investigated immune responses to a panel of sy
nthetic peptides based on the HLA-B27-homologous portions of pathogen-
specific antigens in patients with reactive arthritis and ankylosing s
pondylitis. One third of the patients have antibodies to the synthetic
peptides. However, instead of recognizing the HLA-B27-homologous port
ion, the antibodies are directed against the flanking sequences of the
synthetic peptides. The concept of the role of molecular mimicry betw
een HLA-B27 and microbial antigens in the pathogenesis of spondyloarth
ropathies is discussed, with a conclusion that no convincing evidence
for its significance exists at the present.