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SP0015 The detection of microbial dna in the joint
  1. J Gaston
  1. Rheumatology, University of Cambridge, Cambridge, UK

Abstract

Lyme disease, Whipple’s disease and reactive arthritis are clear examples of forms of arthritis caused by bacterial infection, but the idea that infection might be involved in diseases like rheumatoid arthritis (RA) has a long history. Although joints in all of these conditions are usually “sterile” (i.e. no bacteria can be cultured from the joint), molecular methods of detection have demonstrated the presence of bacterial nucleic acids. The fact that ribosomal RNA (rRNA) genes from all bacteria have highly conserved sequences interspersed with species-specific sequences makes it possible to use polymerase chain reaction (PCR) techniques to detect any bacteria present in synovium and synovial fluid by amplification using “universal” primers which identify the conserved sequences, and then sequencing the products to determine the bacteria from which they arises. When this technique has been applied to synovium from RA patients, multiple species of bacteria have been identified, both by PCR (showing the presence of bacterial DNA) and RT-PCR; the latter implies the presence of live bacteria since bacterial rRNA is unstable, unlike DNA. These results cannot be accounted for by artefactual contamination, and suggest that resident bacteria such as gut and skin-derived organisms can find their way to the joint, most probably within phagocytes which have previously engulfed them and then been recruited to the inflamed joint. The same results were obtained when synovial fluid from reactive arthritis patients was tested. However in reactive arthritis, by using species-specific primers, it was also possible to detect the arthritis-triggering organism (Chlamydia, Yersinia) in a proportion of cases. The specific organism was not detected simply by sequencing the product obtained using universal primers, which suggests that the specific organism is a minor component of the total bacterial colonisation of the joint.

Bacterial products such as DNA, LPS and protein antigens may contribute to joint inflammation both as targets of specific immune responses and as adjuvants. Nevertheless, reactive arthritis and RA differ in that the former usually resolves spontaneously; thus the presence of bacteria is not sufficient to cause chronic inflammation and other mechanisms which engender chronicity must be important in RA. Against a background of commensal bacteria it may be difficult to detect specific disease-associated organisms in RA, since specific organisms are in a minority in the joint even in diseases such as reactive arthritis in which they are clearly important in pathogenesis.

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