Affiliations 

  • 1 Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Kuala Lumpur 56000, Malaysia
  • 2 Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway 47500, Malaysia
  • 3 Sunway Medical Centre, Bandar Sunway 47500, Malaysia
  • 4 Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway 47500, Malaysia
Toxins (Basel), 2022 01 11;14(1).
PMID: 35051027 DOI: 10.3390/toxins14010050

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.