ab2002

Mononuclear cell response to enterobacteria and Gram-positive cell walls of normal intestinal microbiota in early rheumatoid arthritis and other inflammatory arthritides

T. Chen¹, M. Rimpiläinen¹, R. Luukkainen², T. Möttönen³, U. Yli-Kerttula⁴, R. Saario⁵, P. Toivanen¹

¹Department of Medical Microbiology, Turku Immunology Center, Turku University, Turku; ²Department of Rheumatology, Satalinna Hospital, Harjavalta; ³Division of Rheumatology, Department of Medicine, Turku University Central Hospital, Paimio; ⁴Division of Rheumatology, Department of Medicine, Tampere University Hospital, Tampere; ⁵Department of Medicine, Turku University Central Hospital, Turku, Finland.

ABSTRACT
Objective
To study whether enterobacteria and Gram-positive bacterial cell walls (BCW) derived from normal intestinal microbiota are involved in the etiopathogenesis of early rheumatoid arthritis (RA).

Methods
Peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) were isolated from patients with early RA (the average duration of 5 months) and the controls (other types of inflammatory arthritis). The mononuclear cell proliferation and tumor necrosis factor-alpha (TNF-a) responses to heat-killed Salmonella enteritidis (SE), Yersinia enterocolitica (YE), and Escherichia coli (EC), and to Gram-positive BCW derived from four common intestinal indigenous bacteria, Eubacterium aerofaciens (EA), Eubacterium limosum (EL), Lactobacillus casei (LC), and Lactobacillus fermentum (LF), and a BCW derived from a pathogen, Streptococcus pyogenes (SP) were investigated.

Results
39% or 56% of patients with early RA showed significant proliferation responses by PBMC or SFMC against enterobacteria, respectively. In other types of arthritis, corresponding figures were 59% or 66%. When BCW were used as antigens, 8.1% or 23% of patients with early RA showed proliferation responses by PBMC or SFMC, respectively. In other types of arthritis the corresponding figures were 7.5% or 35%, respectively. However, TNF-a production by SFMC stimulated by EA BCW, SE, YE or EC, was significantly higher in early RA than in other types of arthritis.

Conclusion
These results suggest that SFMC reacting with enterobacteria or BCW exist in some patients with early RA, but also in other types of inflammatory arthritis. Intestinal bacterial agents may play a role in the etiopathogenesis of RA, but the effect appears to be non-specific.

Key words
Bacterial cell wall, early rheumatoid arthritis, immune response, synovial fluid.

This work was supported by EVO of Turku University Central Hospital.
Please address correspondence to: Dr. T. Chen, Department of Medical Microbiology, Turku Immunology Center, Kiinamyllynkatu 13, Turku University, FIN-20520, Turku, Finland.
E-mail: tonche@utu.fi