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Bacterial epitopes involved in the induction of reactive arthritis
H Stieglitz1, S Fosmire, P E Lipsky
1University of Texas Southwestern Medical Center, Dallas 75235.
Abstract:
A panel of documented arthritogenic Shigella flexneri strains as well as an epidemic-associated non-arthritogenic Shigella sonnei control was used to identify a 2-megadalton plasmid specific to the arthritogenic strains. The plasmid, pHS-2, contains a DNA sequence that encodes a 22-amino acid polypeptide encompassing a pentapeptide homologous to part of the polymorphic region of the alpha-1 domain of HLA-B27. These results suggest that molecular mimicry between arthritogenic bacterial-encoded epitopes and the HLA-B27 molecule may play a role in the development of reactive arthritis.
Insights
Researchers found a plasmid in arthritogenic Shigella flexneri strains that may cause reactive arthritis. This plasmid contains a sequence mimicking the HLA-B27 molecule, suggesting molecular mimicry plays a role in disease development.
Area of Science:
- Microbiology
- Immunology
- Genetics
Background:
- Reactive arthritis is a condition linked to certain bacterial infections.
- The human leukocyte antigen B27 (HLA-B27) is strongly associated with reactive arthritis.
- The exact mechanisms linking bacterial infections to HLA-B27-associated arthritis remain unclear.
Purpose of the Study:
- To identify specific bacterial factors associated with arthritogenic Shigella strains.
- To investigate potential molecular mechanisms underlying reactive arthritis development.
Main Methods:
- Comparative analysis of arthritogenic Shigella flexneri strains and non-arthritogenic Shigella sonnei controls.
- Plasmid DNA isolation and characterization.
- DNA sequencing to identify relevant genes and encoded polypeptides.
- Bioinformatic analysis to assess sequence homology.
Main Results:
- A 2-megadalton plasmid, designated pHS-2, was identified exclusively in arthritogenic Shigella flexneri strains.
- The pHS-2 plasmid encodes a 22-amino acid polypeptide.
- This polypeptide contains a pentapeptide sequence homologous to a region of the HLA-B27 alpha-1 domain.
Conclusions:
- The pHS-2 plasmid may be a key factor in the arthritogenicity of specific Shigella strains.
- Molecular mimicry between bacterial epitopes encoded by pHS-2 and the HLA-B27 molecule is a potential mechanism for reactive arthritis.
- This finding provides insight into the pathogenesis of HLA-B27-associated reactive arthritis.