Identification of a 2-Md plasmid from Shigella flexneri associated with reactive arthritis

The development of reactive arthritis, a sterile inflammatory polyarthropathy that primarily affects HLA-B27 positive individuals, has been associated with previous enteric infections caused by various gram-negative bacteria. The possibility that a common bacterial epitope triggers the disease was investigated by screening a panel of documented arthritogenic Shigella strains as well as 2 epidemic-associated nonarthritogenic Shigella controls. A 2-Md plasmid specific to the arthritogenic strains was identified and sequenced. The plasmid encodes a number of small peptides that could be related to the development of reactive arthritis. Within 1 of these is a stretch of 5 consecutive amino acids, inferred from the DNA sequence and contained within an open reading frame, that is homologous to amino acid residues 71-75 of the polymorphic region of the alpha 1 domain of HLA-B27. The data indicate that there is a bacterial plasmid common to arthritogenic Shigella strains that may play a role in triggering reactive arthritis. The finding that this plasmid encodes an epitope shared with HLA-B27 suggests that molecular mimicry may play a role in the induction of this disease.