Recently, a number of studies have pointed to a potential relationship between periodontitis (PO) and RA and vice versa. Both diseases are characterized by chronic inflammation, osseous destruction, damage of the supporting soft tissues, similar cellular immune responses and common immunogenetic findings. Although a definite, methodological report associating these diseases is missing from the literature, it is possible that both diseases share a common aetiopathogenic background. This background includes the post-translation modification citrullination, which guides the conversion of the amino acid arginine to citrulline in certain self-proteins, generating neo-epitope structures. This results in reduced self-tolerance, development of autoimmunity and the production of ACPAs. The current hypothesis suggests that certain oral bacteria induce the citrullination of proteins under the action of the enzyme peptidyl arginine deiminase (PAD), which exists in both Porphyromonas gingivalis and inflammatory cells. Antibodies against citrullinated proteins and peptides constitute a common serological finding in both RA and PO. The aim of this review is to map the immunological and serological profiles of PO, and to unveil the parameters that connect PO with the appearance of RA at clinical, prognostic and pathogenetic levels. Until now, there have been no reports sufficiently mapping the immunological profile of PO and defining its aetiopathogenic connection with RA, although a similarity between the immunological profile of PO and RA is highly expected.

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SummaryAnti-citrullinated peptide antibodies (ACPA) are highly specific for rheumatoid arthritis (RA). However, the predominant B cell epitopes have not yet been defined. The aim of this study was to examine the reactivity of ACPA against different peptides derived from citrullinated proteins and to investigate whether or not these antibodies constitute a homogeneous population. For this purpose, sera from patients with RA (n = 141), systemic lupus erythematosus (SLE) (n = 60), Sjögren's syndrome (SS) (n = 54) and healthy controls (n = 100) were tested for their reactivity against six citrullinated peptides derived from peptidyl arginine deiminase (PAD), vimentin (vim), alpha-enolase (enol), fibrin, type II collagen (col-II) and filaggrin, respectively. A non-citrullinated control peptide derived from PAD was used as control (ctrlPAD 621-40 ). Antibody reactivity against each individual peptide was evaluated by enzyme-linked immunosorbent assay (ELISA). Specificity and cross-reactivity of ACPA were tested by using two prototype sera with homologous and cross-inhibition assays. Specificity of ACPA from two prototype sera was confirmed by purification of anti-peptide antibodies and homologous-inhibition experiments. We found that sera from patients with RA reacted diversely with the six citrullinated peptides. More specifically, PAD 211-30 displayed 29·08% sensitivity, vim 60-75 29·08%, enol 5-21 37·59%, fibrin 617-31 31·21%, col-II 358-75 29·97% and filaggrin 306-24 28·37%, while control ctrlPAD 621-40 showed no reactivity. All reactive peptides were found to be highly specific for RA. A notable cross-reaction (>70%) was found mainly between filaggrin and the majority of anti-citrullinated peptide antibodies. We concluded that ACPA in RA constitute a heterogeneous population with limited cross-reactivity and without a predominant epitope.