Aggregatibacter actinomycetemcomitans as the Aetiological Cause of Rheumatoid Arthritis: What Are the Unsolved Puzzles?

Leukotoxin A (LtxA) is the major virulence factor of an oral bacterium known as Aggregatibacter actinomycetemcomitans (Aa). LtxA is associated with elevated levels of anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients. LtxA targets leukocytes and triggers an influx of extracellular calcium into cytosol. The current proposed model of LtxA-mediated hypercitrullination involves the dysregulated activation of peptidylarginine deiminase (PAD) enzymes to citrullinate proteins, the release of hypercitrullinated proteins through cell death, and the production of autoantigens recognized by ACPA. Although model-based evidence is yet to be established, its interaction with the host's immune system sparked interest in the role of LtxA in RA. The first part of this review summarizes the current knowledge of Aa and LtxA. The next part highlights the findings of previous studies on the association of Aa or LtxA with RA aetiology. Finally, we discuss the unresolved aspects of the proposed link between LtxA of Aa and RA.

A retrospective study of the accuracy between clinical and autopsy cause of death in the University of Malaya Medical Centre.

It is well known that diagnostic accuracy of the clinical cause of death has not improved despite advances in diagnostic techniques. We aimed to investigate the accuracy of the clinical cause of death compared with the autopsy cause of death and to see if the Coroner's autopsy can play a role in clinical audit. Our study population consisted of all autopsies where the deceased was hospitalised or resuscitated at the Accident and Emergency Unit of the University of Malaya Medical Centre before death, performed during the period July 1998 to June 2000. The cases were subdivided according to natural and unnatural causes of deaths. Natural deaths were further subdivided in relation to the main organ systems involved while unnatural deaths were subcategorised into trauma, poisoning and burns. The rate of agreement between clinical and autopsy cause of death was further compared with duration of survival in the hospital. Of 132 autopsies included in this study, 115 were Coroner's autopsies. 78% of cases showed agreement between clinical and autopsy cause of death. The agreement rate in Coroner's cases was 80.0%. For natural and unnatural causes, the agreement rate was 56.7% and 84.3% respectively. There were 6 cases (4.5%) where an initial accurate diagnosis might have altered the prognosis of the deceased. In general, the rate of agreement increased with duration of survival of patients. However, this was no longer observed after a survival of more than 28 days. Our findings agree with other similar studies. The diagnostic accuracy of cause of death has not improved despite the modernisation in medical technology. The autopsy still plays an important role in clinical audit and medical education.