The goal of the project is to obtain information about host-microbe interactions in vivo and in vitro in order to understand the mechanisms determining the development of reactive arthritis in some HLA-B27 positive persons, eg. after Salmonella and Yersinia infections. There is evidence that elimination of causative bacteria is not effective in HLA-B27 positive persons developing reactive arthritis, but these bacteria/bacterial antigens persist in the patients for long times, even for years. Elimination of these bacteria is impaired also in vitro, in HLA-B27-transfected monocytic cells and in monocytes/macrophages from HLA-B27 positive persons with reactive arthritis in the past. Both in vivo and in vitro, activation of HLA-B27 positive cells is different compared to HLA-B27 negative cells when infected with causative bacteria or stimulated with bacterial antigens. Knowledge about the exact mechanisms leading to impaired elimination of causative bacteria can help to find effective treatments and prevention of these diseases in HLA-B27 positive persons.

• Mechanisms leading to the persistence of reactive arthritis-triggering bacteria in HLA-B27 positive patients with reactive arthritis
• Possible role of bacterial infections/bacterial antigens in the pathogenesis of ankylosing spondylitis
• Mechanisms leading to impaired elimination of Salmonella and Yersinia in HLA-B27-transfected monocytic cells
• Intracellular survival of Salmonella and Yersinia in monocytes/macrophages from HLA-B27 positive and negative persons in vitro
• Activation of HLA-B27 positive and negative monocytes during Salmonella infection, and during stimulation with Salmonella LPS
• Modification of Salmonella virulence genes by HLA-B27 positive host cells

• Penttinen, M.A., Holmberg, C.I., Sistonen, L. & Granfors, K. HLA-B27 modulates nuclear factor kB activation in human monocytic cells exposed to lipopolysaccharide. Arthritis Rheum 46: 2172-2180, 2002.
  
  PubMed - abstract

• Saarinen, M., Ekman, P., Ikeda, M., Virtala, M., Grönberg, A., Yu, D.T.Y., Arvilommi, H. & Granfors, K. Invasion of Salmonella into human intestinal epithelial cells is modulated by HLA-B27. Rheumatology 41: 651-657, 2002.
  
  PubMed - abstract

• Granfors, K., Märker-Hermann, E., de Keyser, F., Khan, M.A., Veys, E.M. & Yu, D.T.Y. The cutting edge of spondyloarthropathy research in the millenium. Arthritis Rheum 46: 606 -613, 2002.
  
  PubMed - abstract

• Ekman, P., Saarinen, M., He, Q., Gripenberg-Lerche, C., Grönberg, A., Arvilommi, H. & Granfors, K. HLA-B27-transfected (Salmonella-permissive) and HLA-A2-transfected (Salmonella-nonpermissive) human monocytic U937 cells differ in their production of cytokines. Infect Immun 70: 1609-1614, 2002.
  
  PubMed - abstract

• Ekman, P., Kirveskari, J. & Granfors, K. Modification of disease outcome in Salmonella patients by HLA-B27. Arthritis Rheum 43:1527-1534, 2000.
  
  PubMed - abstract

• Kirveskari, J., He, Q., Holmström, T., Leirisalo-Repo, M., Wuorela, M., Mertsola, J. & Granfors, K. Modulation of peripheral blood mononuclear cell activation status during Salmonella-triggered reactive arthritis. Arthritis Rheum 42:2045-2054, 1999.
  
  PubMed - abstract

• Gaston, J. S. H., Cox, C. & Granfors, K. Clinical and experimental evidence for persistent Yersinia infection in reactive arthritis. Arthritis Rheum 42:2239-2242, 1999.
  
  PubMed - abstract

• Kirveskari, J., He, Q., Leirisalo-Repo, M., Mäki-Ikola, O., Wuorela, M., Putto-Laurila, A. & Granfors, K. Enterobacterial infection modulates major histocompatibility complex class I expression on mononuclear cells. Immunology 97:420-428, 1999.
  
  PubMed - abstract

• Wuorela, M., Tohka, S., Granfors, K. & Jalkanen, S. Monocytes that have ingested Yersinia acquire enhanced capacity to bind to non-stimulated vascular endothelium via P-selectin. Infect Immun 67:726-732, 1999.
  
  PubMed - abstract

• Kirveskari, J., Jalkanen, S., Mäki-Ikola, O. & Granfors, K. Increased synovial endothelium binding and transendothelial migration of mononuclear cells during Salmonella infection. Arthritis Rheum 41:1054-1063, 1998.
  
  PubMed - abstract

• Granfors, K., Merilahti-Palo, R., Luukkainen, R., Möttönen, T., Lahesmaa, R., Probst, P., Märker-Hermann, E. & Toivanen, P. Persistence of Yersinia antigens in peripheral-blood cells from patients with Yersinia enterocolitica O3 infection with or without reactive arthritis. Arthritis Rheum 41:855-862, 1998.
  
  PubMed - abstract

• Laitio, P., Virtala, M., Salmi, M., Pelliniemi, L. J., Yu, D.T.Y. & Granfors, K. HLA-B27 modulates intracellular survival of Salmonella enteritidis in human monocytic cells. Eur J Immunol 27:1331-1338, 1997.
  
  PubMed - abstract

Doctoral Theses

• Mononuclear phagocytes and the pathogenesis of Yersinia-triggered reactive arthritis. Maarit Wuorela, 1996.
• Salmonella-triggered reactive arthritis. Mononuclear cells and pathogenesis. Juha Kirveskari, 1998.
• Host-microbe interaction in intestinal epithelium: A special reference to arthritogenic bacteria and nitric oxide. Marja Saarinen, 1999.
• Host-microbe interactions in Salmonella-triggered reactive arthritis. With special reference to HLA-B27. Päivi Ekman, 2000.