Porphyromonas gulae y los anticuerpos PPAD no están relacionados con la citrulinación en la artritis reumatoide

Introducción: Porphyromonas gulae posee la enzima PPAD, al igual que P. gingivalis, responsable de la citrulinación relacionada con la fisiopatología de la artritis reumatoide y la periodontitis; esto implica la presencia de dos especies de bacterias productoras de PPAD en la boca, así como la presencia de proteínas citrulinadas. No existen informes ni estudios previos que investiguen una asociación entre la PPAD de P. gulae en la artritis reumatoide (AR). Objetivo: Evaluar la presencia de P. gulae y anticuerpos antipéptido citrulinado de P. gulae PAD en pacientes con AR y su posible relación con marcadores de actividad clínica. Sujetos y métodos: Se incluyeron un total de 95 pacientes con AR y 95 controles. Se midieron la velocidad de eritrosedimentación (VSG), la proteína C reactiva, los anticuerpos antiproteínas citrulinadas (ACPA) y el factor reumatoide (FR). Índice de actividad-28 (DAS28) y SCDAI. Se estableció el diagnóstico periodontal. Presencia de P. gulae y P. gingivalis. Se utilizó un ELISA para determinar anticuerpos contra los péptidos citrulinados del PAD de P. gulae. Resultados: Se observó una frecuencia de P. gulae del 15,8% en el grupo AR y del 9,5% en el grupo control. Se encontraron mayores niveles de ACPA en los pacientes P. gulae-positivos del grupo AR, sin encontrar diferencias significativas, pero si en los pacientes positivos para P. gingivalis con significación estadística (p = 0,0001). La frecuencia de anticuerpos anti-VDK-cit y anti-LPQ-cit9 frente a PPAD de P. gulae fue mayor en el grupo AR que en el grupo control sin diferencia significativa. No se halló ninguna relación con las variables clínicas a pesar de la presencia de anticuerpos contra el péptido P. gulae y anticuerpos antipéptido citrulinado de la PPAD de P. gulae en pacientes con AR Conclusiones: No fue posible establecer una conexión con las variables clínicas en AR y P. gulae; como resultado, la presencia de P. gingivalis sigue contribuyendo significativamente al aumento de anticuerpos contra proteínas/péptidos citrulinados de fuentes exógenas de citrulinación en AR y periodontitisIntroduction: Porphyromonas gulae have the enzyme PPAD, as P. gingivalis, which is responsible for citrullination related to the pathophysiology of rheumatoid arthritis and periodontitis; this implies the presence of two species of PPAD-producing bacteria in the mouth as well as the presence of citrullinated proteins. There are no previous reports or studies investigating an association between P. gulae PPAD in rheumatoid arthritis (RA). Objective: To assess the presence of P. gulae and anti-citrullinated peptide antibodies of P. gulae PAD in patients with RA and their possible relationship with clinical activity markers. Subjects and methods: A total of 95 patients with RA and 95 controls were included. Erythrocyte sedimentation rate (ESR), C-reactive protein, anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) were measured. Activity index-28 (DAS28) and SCDAI. The periodontal diagnosis was established. Presence of P. gulae and P. gingivalis. An ELISA was used to determine antibodies against citrullinated peptides of P. gulae PAD. Results: A P. gulae frequency of 15.8% was observed in the RA group and 9.5% in the control group. Higher levels of ACPA were found in the P. gulae-positive patients of the RA group, finding no significant difference, but if in patients positive for P. gingivalis with statistical significance (p = 0.0001). The frequency of anti-VDK-cit and anti-LPQ-cit9 antibodies to PPAD of P. gulae was higher in the RA group than in the control group without significant difference. No relationship was found with the clinical variables despite the presence of P. gulae and anti-citrullinated peptide antibodies of P. gulae PPAD in patients with RA Conclusions: It was not possible to establish a connection with clinical variables in RA and P. gulae; as a result, the presence of P. gingivalis continues to contribute significantly to the increase in antibodies against citrullinated proteins/peptides from exogenous sources of citrullination in RA and periodontitis

Anti-carbamylated protein and peptide antibodies as potential inflammatory joint biomarkers in the relatives of rheumatoid arthritis patients

*Q3Objective: Antibodies against carbamylated proteins/peptide (CarP) have been associated with severity in rheumatoid arthritis (RA) patients. However, their role in risk groups, specific targets and relation with periodontal disease (PD) is uncertain yet. The aim of this study was evaluated the association between the levels of anti- CarP with clinical manifestation, human leukocyte antigen (HLA) alleles, periodontal activity markers, PD diagnosis, PD severity, and presence of Porphyromonas gingivalis (P gingivalis) in relatives of patients with RA. Methods: One hundred and twenty-four individuals with a family history of RA in first-degree relatives (FDR) and 124 healthy individuals gender- and age-matched, RA activity was assessed. Antibodies against carbamylated protein anti-FCS-Carp and 2 carbamylated peptides of fibrinogen were selected (anti-Ca-Fib2, anti-Ca-Fib3). Results: Anti-FCS-Carp-positive, anti-Ca-Fib2 and anti-Ca-Fib3 were more frequent in FDR than controls (25.0% vs 14.5%, 34.7% vs 15.3% and 33.1% vs 11.3%, respectively). Anti-FCS-CarP were associated with the HLA-DRB1-SE* 1402 allele (P = .035) and highly sensitive C-reactive protein levels (P = .016), the anti-Ca-Fib2 antibodies were associated with the HLA-DRB1-SE* 1501 allele (P = .03), with non-SE* 0901 allele (P = .01), the anti-Ca-Fib3 was associated with positive rheumatoid factor (P = .0012). The FDR condition was associated with the presence of anti-Ca-Fib3 (odds ratio [OR] =4.7; 95% CI = 1.8-11.7; P = .001) and painful joints (OR = 2.2; 95% CI = 1.01-4.68; P = .045); we also detected an important trend toward the presence of P gingivalis (OR = 1.9; 95% CI = 0.9-3.7; P = .062). Conclusion: The presence of anti-FCS-Carp, anti-Ca-Fib3 and anti-Ca-Fib2 antibodies may have a role for these antibodies as early biomarkers in the development of RA, probably including additional mechanisms related with other non-SE alleles; the anti-peptide antibodies proposed in the present study may represent a simpler way to identify antibodies directed to a specific target.N/

P050 Oral inflammatory changes associated with inflammatory bowel disease in spondyloarthritis associated with early endoscopic findings

BACKGROUND: Spondyloarthritis (SpA) is a heterogeneous group of chronic autoinflammatory disorders that can present extra-articular gastrointestinal manifestations. Among them is mainly inflammatory bowel disease (IBD). Although IBD mainly affects the intestinal tract, it can include early manifestations evident in the oral cavity. No comparative data on these oral manifestations in patients with SpA were found in the literature. OBJECTIVE: To identify oral clinical manifestations due to changes in the oral mucosa associated with IBD in patients with SpA without a diagnosis of IBD and associate them with endoscopic and histological findings. METHODS: 80 patients with SpA and 52 healthy controls were evaluated. They were assessed intra- and extra-orally, following the modified World Health Organization guideline. In addition, by clinical parameters of rheumatological, gastrointestinal and laboratory activity. Ileocolonoscopy was performed with digital chromoendoscopy with magnification and histological analysis. Comparative analyzes were performed by Chi square tests, Fisher's exact tests, confirmed by univariate regression and discriminant analysis of multiple correspondences. Institutional ethics committee approval cod-2017-023. RESULTS: The patients with SpA had 56% male gender, mean age of 42.8 years (SD ± 10.4) and a BMI in the range of 23.9 - 28.4. The healthy controls, 54% of the male gender with an average age of 41 years (SD ± 13.6) and a body mass index-BMI in the range of 22.9 - 27.6. The patients reported smoking only in 6.2%, however as a smoking history in 31% and passive smokers (15%), the majority employed (41%), married (56%) and professionals (49%). Of the healthy controls, they smoked (15%), with a history of smoking (31%), passive smokers (21%), the majority employed (77%), with their own home (67%), and professionals (54%). The patients with SpA reported a greater presence of some signs and symptoms of gastrointestinal origin 69%, while in the controls it was 7.7% (p = 0.001). Forty one of them were referred to colonoscopy with magnification being in 17.1 % changes in the mucosa of the rectum and in the same frequency changes in the mucosa of the sigmoid colon. Regarding the ileum, changes in the mucosa were evidenced in 41.5% of the cases. The presence of oral lesions was evident and predominated in them (63%) compared to controls p = 0.050. The main oral lesions associated with IBD were gingivitis (55%) (p = 0.001), followed by aphthous stomatitis (3.8%), angular cheilitis (2.6%) and perioral erythema with scaling (1.3%). 100% of the patients who presented alteration of the colonic mucosa presented oral lesions associated with IBD (p = 0039), which was also significantly associated with the presence of gingivitis/aphthous stomatitis (p = 0.029). CONCLUSION: Patients with SpA without a diagnosis of IBD have more oral signs and symptoms compared to healthy controls. Gingivitis is important given its association with early endoscopic and histological findings. Manifestations in the oral cavity can precede intestinal manifestations, therefore the clinical assessment by the oral pathologist in conjunction with gastroenterology and rheumatology allows a timely referral to gastroenterology and an endoscopic and histological evaluation, impacting the quality of life of patients

HLA-B Allele, Genotype, and Haplotype Frequencies in a Group of Healthy Individuals in Colombia

6 páginasBackground The sequencing of alleles of the HLA-B, a human leukocyte antigen (HLA) class I gene, was established as the most polymorphic of chromosome 6 and of the entire human genome. In this locus, the HLA-B*27 allele is highly polymorphic and has clinical relevance. Literature about the subtypes and singular frequency of these alleles in Colombia’s healthy population is scarce. Objective The aim of this study was to establish the HLA-B allele, genotype, and haplotype frequencies in a healthy Colombian population and analyze their association with the sex and geographical distribution of the individuals studied. Methods This is a nonexperimental and descriptive study. The data from whole-blood samples whose HLA genes were genotyped by protocol with the Luminex 100/200 xMAP technology were evaluated. HLA-B*27 positivity was confirmed by the new-generation sequencing technology. The associations between the HLA-B alleles and demographic variables were evaluated by χ2 and Fisher exact tests. Results Twenty-seven HLA-B genotypes were identified in 255 individuals, with the highest frequencies for HLA-B*35 (44.7%), B*40 (19.6%), and B*44 (16.8%). Additionally, 89 HLA-B alleles were found; the most common were HLA-B*35:01 (6.7%) and B*40:02 (6.5%). Nine individuals tested positive for the HLA-B*27 allele with genotype and allele frequencies of 3.5% and 1.8%, respectively; the HLA-B*27:05:02 subtype predominated. Conclusions Here, we report the most common HLA-B allele, genotype, and haplotype frequencies in a healthy Colombian population group and analyzed their association with the sex and geographical distribution of the individuals studied. Results for the HLA-B*27 allele confirm racial mixing in Colombia with a high degree of Caucasian influence, as well as the repopulation of Colombia's central region, attributed to the migration phenomena. Results agree with data published in Colombia that was obtained from cord blood samples

Adipokines and periodontal markers as risk indicators of early rheumatoid arthritis: a cross-sectional study

Objective: To establish the association between adipokine levels and markers of periodontal involvement as risk indicators of early stages of RA (eRA) and the interaction between the presence of markers of periodontal disease with adipokine in eRA individuals. Materials and methods: Fifty-one patients with a diagnosis of eRA and 51 healthy controls matched for age and sex were studied. Clinical joint condition, clinical and serological markers of disease activity, serum adipokine levels (leptin, adiponectin, resistin, adipsin, vaspin, and IL-6), periodontal diagnosis, presence of Porphyromonas gingivalis, and related IgG1 and IgG2 antibodies were evaluated. Comparisons were made between eRA and healthy controls for periodontal indicators and adipokines. A subgroup analysis was realized with a non-conditional logistic regression to establish the association between the levels of leptin in individuals with eRA and controls according to the periodontal condition, presence of P. gingivalis, or high titers of IgG antibodies against P. gingivalis. Results: The condition of overweight or obesity is associated with the diagnosis of eRA (p = 0.05), and these individuals also have higher levels of leptin (p = 0.001) and vaspin (p = 0.007). Higher frequency of P. gingivalis (p = 0.001) was found in the eRa group. Individuals with eRA with higher IgG2 titers against P. gingivalis had higher levels of leptin (OR: 1.66 (CI 95% 1.01–2.73)); however, individuals with periodontitis or P. gingivalis with eRA were associated with highest levels of leptin (OR: 1.86, CI 95% 1.19–24.3; and OR: 2.04, CI 95% 1.37–3 respectively). Conclusions: eRA individuals have high levels of leptin and vaspin. However, the presence of periodontitis and related-periodontal disease markers showed an effect only in leptin levels in eRA individuals. Clinical relevance: Emphasizing in personalized medicine, monitoring serum leptin levels and periodontitis markers can improve the early diagnosis of RA

HLA-B Allele, Genotype, and Haplotype Frequencies in a Group of Healthy Individuals in Colombia

6 páginasBackground The sequencing of alleles of the HLA-B, a human leukocyte antigen (HLA) class I gene, was established as the most polymorphic of chromosome 6 and of the entire human genome. In this locus, the HLA-B*27 allele is highly polymorphic and has clinical relevance. Literature about the subtypes and singular frequency of these alleles in Colombia’s healthy population is scarce. Objective The aim of this study was to establish the HLA-B allele, genotype, and haplotype frequencies in a healthy Colombian population and analyze their association with the sex and geographical distribution of the individuals studied. Methods This is a nonexperimental and descriptive study. The data from whole-blood samples whose HLA genes were genotyped by protocol with the Luminex 100/200 xMAP technology were evaluated. HLA-B*27 positivity was confirmed by the new-generation sequencing technology. The associations between the HLA-B alleles and demographic variables were evaluated by χ2 and Fisher exact tests. Results Twenty-seven HLA-B genotypes were identified in 255 individuals, with the highest frequencies for HLA-B*35 (44.7%), B*40 (19.6%), and B*44 (16.8%). Additionally, 89 HLA-B alleles were found; the most common were HLA-B*35:01 (6.7%) and B*40:02 (6.5%). Nine individuals tested positive for the HLA-B*27 allele with genotype and allele frequencies of 3.5% and 1.8%, respectively; the HLA-B*27:05:02 subtype predominated. Conclusions Here, we report the most common HLA-B allele, genotype, and haplotype frequencies in a healthy Colombian population group and analyzed their association with the sex and geographical distribution of the individuals studied. Results for the HLA-B*27 allele confirm racial mixing in Colombia with a high degree of Caucasian influence, as well as the repopulation of Colombia's central region, attributed to the migration phenomena. Results agree with data published in Colombia that was obtained from cord blood samples

Association of adipokines with rheumatic disease activity indexes and periodontal disease in patients with early rheumatoid arthritis and their first‐degree relatives

Objective To evaluate the adipokine levels in early rheumatoid arthritis (eRA) and first‐degree relatives (FDR) of patients with RA and establish their association with rheumatic disease activity and periodontal variables. Method A cross‐sectional study with eRA patients, FDR and a healthy population. Adipokine levels, clinical, joint radiological indexes and periodontal variables were evaluated. A descriptive, bivariate analysis was performed based on the adipokine levels by χ2, Fisher's test and Mann–Whitney U test. A logistic regression was made for associations. Results High leptin levels were associated with the diagnosis of eRA (odds ratio [OR] = 2.79; 95% CI 1.54‐5.07). Early rheumatoid arthritis with high adiponectin levels was less likely to have Multidimensional Health Assessment Questionnaire score >3, body mass index (BMI) >25 and Routine Assessment of Patient Index Data 3 score >12 (OR = 0.16; 95% CI 0.03‐0.72). Early rheumatoid arthritis was more likely to present high leptin and interleukin (IL)6 levels with low adiponectin simultaneously (OR = 5.03; 95% CI 1.05‐24.0). High leptin levels were associated with the FDR adjusted for IgG2 Porphyromonas gingivalis, swollen joints, P gingivalis and low IL6 (OR = 2.57; 95% CI 1.14‐5.95). Conclusion High adipokine levels in eRA may modulate the disease activity. Having more than 1 adipokine at high serum levels is associated with increased disability, disease activity and BMI, indicating that RA is controlled by adiponectin levels in the early stages of the disease. High leptin levels, presence of P gingivalis and swollen joints may be the factors associated with the development of RA in FDR

Frecuencia de HLA-B27 en una población colombiana con signos de espondiloartritis

12 páginasBackground: The strong association between HLA-B27 and spondyloarthritis (SpA) has demonstrated that typing the HLA-B27 antigen is a crucial step in diagnosis and aids in defining the progression and severity of disease. Objective: To describe the frequency of HLA-B27 in Colombian individuals with clinical manifestations associated with SpA. Materials and Methodology: We retrospectively analyzed 4109 HLA-B27 typing requests to the Hospital Militar Central and the Instituto de Referencia Andino from Colombian individuals with clinical signs suggestive of SpA between 2009 and 2012. We used basic digital cytometry followed by Polymerase Chain Reaction with sequence specific primers when confirmation was needed. We determined the frequency of HLA-B27 in the population and levels of association of HLA-B27 with SpA. Results: Our population included 1585 men (36.8%) and 2524 women (61.4%). The predominant age range was between 19 and 45 years (49.9%). The majority (95.4%) of the study population came from the Andean region and eastern plains. The most frequent clinical manifestations were peripheral. Only a small fraction (12.1%) of the 4109 subjects was HLA-B27 positive. Of those, 56.9% were male, and 54.7% were between 19 and 45 years old. In contrast, when rheumatologists referred the HLA B27, 64% were found to be positive. Conclusion: The frequency of the HLA-B27 allele in individuals with clinical signs suggestive of SpA was low, in accordance with the lower prevalence found in Colombian patients diagnosed with SpA compared to American and European population.Antecedentes: la fuerte asociación entre HLA-B27 y la espondiloartritis (SpA) ha demostrado que la tipificación del antígeno HLA-B27 es un paso crucial en el diagnóstico y ayuda a definir la progresión y la gravedad de la enfermedad. Objetivo: Describir la frecuencia de HLA-B27 en colombianos con manifestaciones clínicas asociadas a EspA. Materiales y Metodología: Analizamos retrospectivamente 4109 solicitudes de tipificación HLA-B27 al Hospital Militar Central y al Instituto de Referencia Andino de individuos colombianos con signos clínicos sugestivos de SpA entre 2009 y 2012. Utilizamos citometría digital básica seguida de Reacción en Cadena de la Polimerasa con secuencia cebadores específicos cuando se necesitaba confirmación. Determinamos la frecuencia de HLA-B27 en la población y los niveles de asociación de HLA-B27 con SpA. Resultados: Nuestra población estuvo compuesta por 1585 hombres (36,8%) y 2524 mujeres (61,4%). El rango de edad predominante fue entre 19 y 45 años (49,9%). La mayoría (95,4%) de la población de estudio provenía de la región andina y llanos orientales. Las manifestaciones clínicas más frecuentes fueron periféricas. Solo una pequeña fracción (12,1 %) de los 4109 sujetos fue HLA-B27 positivo. De ellos, el 56,9% eran hombres y el 54,7% tenían entre 19 y 45 años. En cambio, cuando los reumatólogos derivaron el HLA B27, el 64% resultó positivo. Conclusión: La frecuencia del alelo HLA-B27 en individuos con signos clínicos sugestivos de SpA fue baja, de acuerdo con la menor prevalencia encontrada en pacientes colombianos con diagnóstico de SpA en comparación con la población americana y europea

Could Increase Levels of Dickkopf-1 Protein be Considered As a Potential Biomarker for Bone Resorption in Joint and Periodontal Disease in Patients with Early Rheumatoid Arthritis?

Periodontitis and rheumatoid arthritis (RA) are chronic destructive inflammatory diseases with significant worldwide prevalence. They are characterized by inflammatory lesions adjacent to bone destruction involving connective tissue and bone. Dickkopf-1 (DKK-1) is a major regulator of bone mass; however, their involvement in local bone resorption is largely unknown. The aim of this study was to assess the utility of DKK-1 levels in gingival crevicular fluid (GCF) and serum as a potential predictor of bone loss in periodontal disease and/or early RA