Journal
TOXINS
Volume 14, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/toxins14010050
Keywords
Aggregatibacter actinomycetemcomitans; leukotoxin A; hypercitrullination; rheumatoid arthritis; anti-citrullinated protein antibodies
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Funding
- Sunway Medical Centre [SRB/F/20/005]
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Leukotoxin A (LtxA) is a major virulence factor of the oral bacterium Aggregatibacter actinomycetemcomitans (Aa) and has been found to be 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, leading to hypercitrullination. Although the model-based evidence is yet to be established, the interaction of LtxA with the host immune system has sparked interest in its role in RA.
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.
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