Background Rheumatoid arthritis (RA) is a systemic autoimmune disease that increased bone resorption. Periodontal disease (PD) is an associated risk factor of RA. Studies suggest an association between bone markers such as the dickkopf-related protein 1 (DKK-1) and progression of radiological damage. We aimed to evaluate the marker DKK-1, its polymorphisms in patients with early rheumatoid arthritis (eRA), and its association with rheumatic, radiological, and periodontal variables. Methods This is a cross-sectional study. Samples were obtained from 63 patients with eRA. Radiographs of hands and feet were evaluated by Sharp–van der Heijde score (SHS) and Simple Erosion Narrowing Score (SENS). Serum DKK-1 levels and high-resolution fusion analysis was used for polymorphisms (rs1896368, rs1896367, rs1528873). Bivariate analyses were performed. Results Individuals heterozygous for rs1896367 had more frequent erosions (p = 0.026) and joint space narrowing (p = 0.005) in the feet, higher SHS (p = 0.016), and higher SENS (p ≤ 0.001). Patients homozygous for rs1896368 had less frequent joint space narrowing in hands and feet as assessed by SHS and less presence of erosions by SENS (odds ratio, 0.04; 95% confidence interval, 0.00–0.93; p < 0.05). The presence of PD was associated with the homozygous of rs1896367 (p = 0.009) and the heterozygous of rs1896368 (p = 0.033). Conclusions Polymorphism rs1896367 seems to be associated with greater radiological compromise; rs1896368 confers protection against bone damage in Colombian eRA patients.

BackgroundIgG antibodies against citrullinated peptides are one of the most specific biomarkers used in the classification of the disease. The relationship between RA and periodontal disease is based on the process of citrullination. The enzyme in the most important bacteria related with periodontitis (Porphyromonas gingivalis) the Peptidylarginine Deiminase (PPAD) modify arginine residues to citrullineObjectivesTo model in silico the binding of PPAD peptides with the hypervariable regions of IgGMethodsOne PPAD peptide with 15 residues was selected in silico by its recognition by B cells (Bcepred y ABCpred) and T lymphocytes (ProPred, MHCPred). The peptide arginines were changed in silico by citrulline (Cit) with the ACD/ChemSketch software, obtaining four different peptides, natural, Arg1 changed, Arg1-Arg8 changed and a random sequence. The 3D peptide modelling was obtained using PEP-FOLD Server and the 3D structure of variable domains of the heavy and light chain of lgG was obtained with the SwissModel. The amino acids of the hypervariable regions capable of interacting were defined using ConSurf Server. The peptides and variable domains were prepared using Openbabel. Docking models were performed by Patchdock and PyMOL tool was used to rendering the structural complexes obtainedResultsThe 3D structure of IgG variable domains had a QMEN6 z-score <1. Modelling of the topological disposition of the amino acids was obtained and the interaction scores between the four peptides and light and heavy chain hypervariable regions were high, although the better score was in the natural peptide and light chain interaction. The heavy chain showed also a high score during the in silico interaction with the Cit1-Cit8 modified peptide. The approximate interface area of the receptor-ligand complex and the contact atomic energy (ACE) between the ligand and the receptor revealed the energy required for the interaction allowing its stability. The PPAD-IgG complexes showed the atomic contact maps in which the heavy chain hypervariable region contacted seven amino acids in all four peptides while only six contacts occurred between light chain and the peptides. The model showed the interactions between light chain and natural peptide (Arg1 with Gly100, Arg8 with Glu1) and for Cit1-Cit8 peptide, Cit8 interact with Thr10 (Cit1 has no contact). Regarding the heavy chain, Arg1 of natural peptide interacted with Trp47 while for Cit1-Cit8 peptide were Cit1 with Lys43 and Cit8 with Pro40ConclusionsThe in silico model shows bacterial PPAD peptides with and without citrullination interact with the hypervariable regions of human IgG. The citrulline residues modify the 3D structure influencing the contact area with the heavy and light chain variable regions. Peptide with modifications of two arginine residues by citrulline presented a high interaction score indicating that may have an effective recognition for IgGDisclosure of InterestNone declared

BackgroundRheumatoid arthritis (RA) is an autoimmune disease that primarily affects the joints but also has extra-articular manifestations such as Periodontal Disease (PD). The Dickkopf-1 (DKK-1) may have an active role in the regulation of bone biology and patients with RA that carry genetic variants of DKK-1 have greater bone damageObjectivesTo investigate the polymorphisms of DKK-1 in patients with early RA (eRA) and its association with some rheumatic, radiological and periodontal variables.MethodsA cross-sectional study in 63 patients with eRA according to the ACR/EULAR 2010 criteria and PD based on the AAP/CDC and Prevention criteria. Serum markers rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C reactive protein (CRP) and anticitrullinated peptide antibodies (APCAs) were evaluated. Patients selected were over 18 and less than 65 years old and were on treatment with conventional disease modifying antirheumatic drugs. Rheumatic activity was assessed by scales disease activity score 28 and simplified disease activity index. Radiographs of hands and feet were evaluated using the Sharp-van der Heijde (SvH) and Simple Erosion Narrowing Scores (SENS). DKK-1 polymorphisms as rs1896368, rs1896367 and rs1528873 were determined using the High resolution Melting technique (Bio-Rad). A bivariate analysis was performed to determine the variables associated between polymorphism to the presence of radiological and activity scores, diagnosis and severity of PD. A regression model was performed to confirm these associations.ResultsThe mean age was 48.57±11.35 years, and 76.7% were female. 11.7% had a body mass index >30 kg/m2. 35% had an ESR >20 mm/h, and 56,7% had elevated CRP. RF >20 was observed in 61,7% of patients as were ACPAs>20 in 43,3% of them. 30%, 42% and 1.6% of patients were homozygous for polymorphism rs1896367, rs1896368 and rs1528873 respectively. Individuals heterozygous for polymorphism rs1896367 had more frequent erosions (p=0.026) and joint space narrowing (JSN) (p=0.005) in the feet, and consequently higher SHS scores (p=0.016). These patients also had higher SENS scores (p=0.001) and more frequent erosions (p=0.02). In contrast, patients homozygous for polymorphism rs 1896368 had less frequent JSN in hands and feet as assessed by SHS, as well as less presence of erosions based on the SENS scale. These findings were validated in the regression model (OR: 0.04, 95% CI:0.00–0.93;p<0.05). Finally, the presence of PD was associated with the homozygous expression of polymorphism rs 1896367 (p=0.009) and the heterozygous expression of polymorphism rs1696368 (p=0.033).ConclusionsDKK-1 polymorphisms can be associated with the presence of bone damage in patients with eRA and it could affect periodontal outcomes. While polymorphism rs1696367 seems to be associated with greater radiological compromise, polymorphism rs1696368 confers protection against bone damage in Colombian eRA patients.Reference[1] De Rooy D, et al. Ann Rheum Dis. 2013;72:769–75.Disclosure of InterestNone declared