Analysis of periodontal parameters, subgingival bacteria and levels of LL-37 in periodontitis subjects with rheumatoid arthritis / Cheah Chia Wei
Associations between rheumatoid arthritis (RA), a chronic inflammatory autoimmune disease of the joints, and periodontitis (PD), a chronic inflammatory disease affecting tooth supporting tissues have been reported. Antimicrobial peptide cathelicidin LL-37 besides being antibacterial, is also i...
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| Format: | Thesis |
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2021
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| Online Access: | http://studentsrepo.um.edu.my/13261/ http://studentsrepo.um.edu.my/13261/4/chia_wei.pdf |
| Summary: | Associations between rheumatoid arthritis (RA), a chronic inflammatory autoimmune
disease of the joints, and periodontitis (PD), a chronic inflammatory disease affecting
tooth supporting tissues have been reported. Antimicrobial peptide cathelicidin LL-37
besides being antibacterial, is also involved in inflammatory process. It has been
suggested as a possible mechanistic link for these diseases. This study aimed to
investigate the subgingival microbial profile of RA subjects and its correlation with levels
of salivary and serum LL-37. A total of 104 subjects were allocated into RA (n=49) or
non-RA (NRA) (n=55) groups. Three subgroups, PD, gingivitis (G) and periodontal
health (H) were further established. Demographic, periodontal parameters and
rheumatology data were collected. Subgingival plaque, saliva and serum was sampled.
Extracted plaque DNA was amplified and sequenced on MiSeq platform targeting the 16s
rRNA V3-V4 region. Sequenced data was processed and analysed in CLC Genomic
Workbench (Qiagen) to study characteristics of bacterial communities. Correlations
between bacteria were explored using network analysis and differentially abundant
bacteria were investigated. Serum and salivary LL-37 levels were measured using
enzyme-linked immunosorbent assay (ELISA). The associations between bacteria genera
with disease parameters and LL-37 were explored. Bacterial communities were highly
diverse in all groups while the samples clustered together according to PD conditions.
Phyla Firmicutes, Fusobacteria, Bacteroidetes, Actinobacteria, Proteobacteria,
Patescibacteria and Epsilonbacteraeota were 99% of the total abundance. In the PD
groups, there were higher abundance in phyla Spirochaetes and Synergistetes and
reduction in phyla Actinobacteria and Proteobateria. Highly dense inter-generic
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networks were noted between the genera in the RA-PD group compared to NRA-PD, RA?H or NRA-H. More periodontal disease-associated bacteria genera were observed in RA?PD group. For levels of salivary and serum LL-37, RA-PD showed statistically higher
salivary level compared to all groups. All RA groups and NRA-PD showed statistically
higher serum LL-37 levels compared to NRA-G and NRA-H, but not across the four
groups. Salivary LL-37 positively correlated with ESR and negatively correlated with
CAL in RA-H. Serum LL-37 negatively correlated with number of teeth in NRA-PD; RA
disease duration in RA-H; positively correlated with ESR in RA-G and CRP in RA-H.
Periodontal disease-associated genus positively correlated with periodontal parameters in
NRA-H groups. However, in the rest of the groups, both health- and disease-associated
genera correlated positively with disease parameters. For correlations with salivary and
serum LL-37 similar presentations were exhibited. In conclusion, subgingival microbial
profile was influenced by PD condition. The aberrant immune system in RA-PD
presented as dense network of subgingival microbiota. Severe periodontitis denoted by
fewer number of teeth in NRA-PD showed positive association with serum LL-37.
Positive correlations for serum LL-37 with inflammation were based on associations with
ESR and CRP in RA groups. A dysbiotic oral microbial community was associated with
the inflammatory conditions present in RA and PD. These inflamed conditions increased
the levels of circulating inflammatory cytokines such as LL-37 that may further
dysregulate the host immune balance. The mechanism of subgingival microbial dysbiosis
on LL-37 and the development of RA needs to be further studied.
Keywords: subgingival microbiota, rheumatoid arthritis, periodontitis, LL-37 |
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