TY - JOUR
T1 - Exposure to aggregatibacter actinomycetemcomitans before symptom onset and the risk of evolving to rheumatoid arthritis
AU - Gomez‐Bañuelos, Eduardo
AU - Johansson, Linda
AU - Konig, Maximilian F.
AU - Lundquist, Anders
AU - Paz, Merlin
AU - Buhlin, Kåre
AU - Johansson, Anders
AU - Rantapää‐Dahlqvist, Solbritt
AU - Andrade, Felipe
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/6/2
Y1 - 2020/6/2
N2 - Periodontal disease has been implicated in the pathogenesis of rheumatoid arthritis (RA), an autoimmune disease characterized by immune‐mediated synovial damage, and antibodies to citrullinated antigens. Here, we investigate the association between exposure to the periodontal pathogen Aggregatibacter actinomycetemcomitans (Aa) and the development of RA. IgM, IgG and IgA antibodies to Aa leukotoxin A (LtxA) were detected by ELISA in plasma from a cohort of Swedish adults at different stages of RA development, from before onset of symptoms to established disease. Patients with early and established RA had increased levels of anti‐LtxA IgM compared with matched non‐RA controls and periodontally healthy individuals. Logistic regression revealed that anti‐LtxA IgM levels were associated with RA during early disease (OR 1.012, 95%CI 1.007, 1.017), which was maintained after adjustment for smoking, anti‐CCP antibodies, rheumatoid factor, HLA‐ DRB1 shared epitope alleles and sex. We found no association between anti‐LtxA IgG/IgA antibodies and RA at any stage of disease development. The data support a temporal association between anti‐LtxA IgM antibodies and the development of RA, suggesting that a subset of RA patients may have been exposed to Aa around the time of transition from being asymptomatic to become a patient with RA.
AB - Periodontal disease has been implicated in the pathogenesis of rheumatoid arthritis (RA), an autoimmune disease characterized by immune‐mediated synovial damage, and antibodies to citrullinated antigens. Here, we investigate the association between exposure to the periodontal pathogen Aggregatibacter actinomycetemcomitans (Aa) and the development of RA. IgM, IgG and IgA antibodies to Aa leukotoxin A (LtxA) were detected by ELISA in plasma from a cohort of Swedish adults at different stages of RA development, from before onset of symptoms to established disease. Patients with early and established RA had increased levels of anti‐LtxA IgM compared with matched non‐RA controls and periodontally healthy individuals. Logistic regression revealed that anti‐LtxA IgM levels were associated with RA during early disease (OR 1.012, 95%CI 1.007, 1.017), which was maintained after adjustment for smoking, anti‐CCP antibodies, rheumatoid factor, HLA‐ DRB1 shared epitope alleles and sex. We found no association between anti‐LtxA IgG/IgA antibodies and RA at any stage of disease development. The data support a temporal association between anti‐LtxA IgM antibodies and the development of RA, suggesting that a subset of RA patients may have been exposed to Aa around the time of transition from being asymptomatic to become a patient with RA.
KW - Aggregatibacter actinomycetemcomitans
KW - Anti-citrullinated protein antibodies
KW - Leukotoxin A
KW - Rheumatoid arthritis
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U2 - 10.3390/jcm9061906
DO - 10.3390/jcm9061906
M3 - Article
C2 - 32570853
AN - SCOPUS:85114278889
SN - 2077-0383
VL - 9
SP - 1
EP - 11
JO - Journal of Clinical Medicine
JF - Journal of Clinical Medicine
IS - 6
M1 - 1906
ER -