ab1901

The modulation of chlamydial replication by HLA-B27 depends on the cytoplasmic domain of HLA-B27

J.G. Kuipers, A. Bialowons, P. Dollmann, M.C. Jendro, L. Koehler, M. Ikeda¹, D.T.Y. Yu¹, H. Zeidler

Division of Rheumatology, Department of Internal Medicine, Hannover Medical School, Hannover, Germany; ¹Division of Rheumatology, University of California Los Angeles, California, USA.

ABSTRACT
Objective
The intracellular persistence of viable Chlamydia trachomatis (CT) within the joint is thought to initiate and maintain the inflammatory process in CT-induced arthritis. CT-induced arthritis is associated with HLA-B27. Recently it was shown that HLA-B27, besides being a T-cell restriction element, can directly influence the invasion and/or replication of enterobacteriae and alters salmonella-induced signal transduction. It was the aim of this study to analyze the effect of HLA-B27 on CT-invasion and replication in human host cells.

Methods
Human Hela cells and Hela cells transfected with either HLA-B27 cDNA or controls (HLA-A1 cDNA; HLA-B27 mutant = HLA-B27 without cytoplasmic tail; B27Q10 = HLA-B27 Exon 1-4 linked to Exon 5 of murine Q10) were infected with CT. By direct immunofluorescence chlamydial invasion was determined 4 hours post infection (p.i.), chlamydial replication 2 days and 4 days p.i. The number of infective CT in the different cell lines was determined by titration of the cell lysates on Hep-2 cells with subsequent immunoperoxidase staining.

Results
Invasion was not affected by HLA-B27. However, formation of chlamydial inclusion bodies and replication was suppressed by HLA-B27. Genetically engineered mutants of HLA-B27 (HLA-B27 mutant, B27Q10) lacking the cytoplasmic tail of HLA-B27 did not affect replication.

Conclusion
The reduction of chlamydial replication by HLA-B27 depends on the cytoplasmic domain of HLA-B27, thus providing a new hypothesis for chlamydial persistence in HLA-B27 positive reactive arthritis.

Key words
Chlamydia trachomatis, HLA-B27, reactive arthritis.

This study was supported by the Deutsche Forschungsgemeinschaft, grant number KU 1182/1-1 and 1-3.
Please address correspondence and reprint requests to: Jens Kuipers, MD, Division of Rheumatology, Hannover Medical School, 30623 Hannover, Germany.
E-mail: KUIPERS.JENS@MH-Hannover.DE