[HLA genotypes associated with gastrointestinal symptoms in patients with spondyloarthritis without inflammatory bowel disease]. / Genotipos HLA asociados a síntomas gastrointestinales en pacientes con espondiloartritis sin enfermedad inflamatoria intestinal.

OBJECTIVE: This study aimed to establish the association between HLA-A, B, DR genotypes and gastrointestinal variables in patients with SpA without inflammatory bowel disease (IBD). METHODS: Retrospective study of 91 patients with SpA and 401 healthy controls, with typing by Illumina Sequencing/PacBio and LIFECODES HLA-PCR/SSO multiplex sequencing technology. The presence of gastrointestinal symptoms was evaluated by administering a survey, and those who presented 2 or more symptoms were taken for clinical evaluation by rheumatology and gastroenterology, colonoscopy and histopathological study. (Ethics committee approval). RESULTS: The 59,3% of the patients were men, with a mean age of 43,9±11.4 years; 80,2% were classified as ankylosing spondylitis. 14, 28 and 19 genotypes for the HLA-A*, HLA-B* and HLA-DR* loci were identified in both groups, of which a relationship with gastrointestinal symptoms was identified: A*26, A*29 and B*27 were associated to abdominal pain, DRB1*11 and DRB1*16 with abdominal distention, A*30, B*38, DRB1*13 and DRB1*14 with weight loss, B*40 with diarrhea >4 weeks, and presence of mucus in the stools with A*02 and DRB1*11 (p<0.05). Furthermore, the presence of B*15 had a statistical relationship with intolerance to some food, highlighting the B*27 genotype in relation to grains and dairy products, A*23 with grains, vegetables and meats, and B*49 with vegetables and dairy (p<0.05). Regarding the endoscopic variables, macroscopic changes were found in the ileum mucosa related to A*02, B*48, DRB1*14 and the relationship between B*27 and ulcers at this level should be highlighted. Macroscopic changes in the sigmoid colon with B*48 and the rectum with A*30. In microscopic changes, inflammatory alterations of the ileum are mentioned with genotypes DRB1*07, DRB1*13 and DRB1*14, a genotype that is related to changes in the ileum both endoscopically and histologically (p<0.05). CONCLUSIONS: These findings indicate a potential genetic predisposition related to HLA genotypes that may increase the likelihood of food intolerance, gastrointestinal symptoms, and even visible and microscopic changes, specifically in the ileal tissue. The study highlights the presence of B*27 and other noteworthy HLA class I and class II genes (such as DRB1*14) in the diverse Colombian population.

OBJETIVO: Establecer la asociación entre genotipos HLA-A, B, DR y variables gastrointestinales en pacientes con EspA, sin enfermedad inflamatoria intestinal (EII). MÉTODOS: Estudio retrospectivo de 91 pacientes con EspA y 401 controles sanos, con tipificación por tecnología de secuenciación Illumina Sequencing/PacBio, y LIFECODES HLA-PCR/SSO multiplex. Se evaluó la presencia de síntomas gastrointestinales por aplicación de una encuesta, y, aquellos que presentaran dos o más síntomas, fueron llevados a valoración clínica por reumatología y gastroenterología, colonoscopia y estudio histopatológico. (Aprobación del Comité de Ética, HMC, 2022 - 2020). RESULTADOS: El 59,3% de los pacientes fueron hombres, con edad media de 43,9 ± 11,4 años. El 80,2% se clasificó como espondilitis anquilosante. Se identificaron en ambos grupos 14, 28 y 19 genotipos para los loci HLA-A*, HLA-B* y HLA-DR*, de los cuales se identificó relación con síntomas gastrointestinales: A*26, A*29 y B*27, con dolor abdominal; DRB1*11 y DRB1*16, con distensión abdominal; A*30, B*38, DRB1*13 y DRB1*14, con pérdida de peso; B*40, con diarrea >4 semanas y presencia de moco en las deposiciones con A*2 y DRB1*11 (p<0,05). Además, la presencia de B*15, tuvo relación estadística con intolerancia a algún tipo de alimento, a resaltar el genotipo B*27, en relación con granos y lácteos; A*23 con granos, verduras y carnes; y el B*49, con verduras y lácteos (p<0,05). Frente a las variables endoscópicas, se encontraron cambios macroscópicos en la mucosa de íleon relacionados con A*02, B*48, DRB1*14 y, a destacar, la relación B*27 con úlceras a este nivel. Cambios macroscópicos en colon sigmoides con B*48 y en recto con A*30. En cambios microscópicos, se mencionan alteraciones inflamatorias de íleon con genotipos DRB1*07, DRB1*13 y DRB1*14, genotipos que se relaciona a cambios en íleon tanto endoscópica e histológicamente (p<0,05). CONCLUSIONES: Estos resultados sugieren una posible susceptibilidad genética asociada al HLA, con genotipos que pueden predisponer a intolerancia alimentaria, síntomas gastrointestinales, e incluso, a cambios macroscópicos e histológicos, particularmente en tejido de íleon, entre los cuales está presente el B*27, pero resaltan otros interesantes en HLA clase I, como clase II (DRB1*14), en una población de alto mestizaje como la colombiana.

Gene variants for the WNT pathway are associated with severity in periodontal disease.

OBJECTIVE: Studies of Wnt variants-related to bone resorption in periodontitis are limited. The aim of this study was to establish the genotype and allele frequency of gene variants associated with the Wnt pathway in systemically healthy individuals with and without periodontitis (PD). MATERIALS AND METHODS: One hundred fifty-seven systemically healthy individuals were evaluated, 90 with PD and 67 without PD. Periodontal clinical indexes, serological and clinical indices of inflammation, and the following variants associated with the Wnt pathway: DKK, SOST, LRP5, and KREMEN were analyzed by high resolution melting and confirmed by Sanger sequencing. RESULTS: In the PD-free group, 67.2% of the individuals presented the variant for DKKrs1896367 (p = 0.008) and 82.6% had the variant for KREMEN rs132274 (p = 0.016). The heterozygous variant for the DKK rs1896367 polymorphism was associated with the absence of PD and lower severity OR: 0.33 (CI95% 0.15-0.70) and OR: 0.24 (CI95% 0.11-0.53), respectively. Similarly, KREMEN rs132274 was the homozygous variant associated with the absence of PD (OR: 0.33 (CI95% 0.13-0.88)). On the contrary, 85.6% of individuals with PD presented a variant for DKK rs1896368 (p = 0.042), all suffering severe forms of periodontitis. CONCLUSION: The presence of DKKrs1896367 and KREMENrs132274 variants in individuals without PD suggests that these single nucleotide polymorphisms could be protective factors for bone loss in PD. A very interesting finding is that the DKKrs1896368 variant was found in a high percentage of severe cases, suggesting that the presence of this variant may be related to the severe bone loss observed in PD.

Porphyromonas gulae and PPAD antibodies are not related to citrullination in rheumatoid arthritis.

INTRODUCTION: 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.

High Levels of Leptin and Adipsin Are Associated with Clinical Activity in Early Rheumatoid Arthritis Patients with Overweight and Periodontal Infection.

Adipokines are associated with the pathogenesis of rheumatoid arthritis (RA) and are potential biomarkers of disease activity, periodontitis, and obesity. The aim of this was to establish the association between adipokine profile, RA disease activity, body mass index, and periodontal infection. This study evaluated 51 patients with early-RA and 51 controls including serum rheumatological markers, adipokine levels, detection of Porphyromonas gingivalis and serum anti-Porphyromonas gingivalis antibodies, clinical and periodontal measurements. Statistical analyses were run with SPSS® V26, with a logistic regression model to confirm associations. The results show high levels of leptin were more frequent in patients (p = 0.001) who simultaneously showed a higher frequency of Porphyromonas gingivalis (p = 0.004). Patients with concomitant presence of Porphyromonas gingivalis, high clinical activity score, and overweight were correlated with high levels of leptin (OR, 7.20; 95% CI, 2.68-19.33; p = 0.0001) and adipsin (OR, 2.69; 95% CI, 1.00-7.28; p = 0.005). The conclusion is that high levels of leptin and adipsin are associated with greater clinical activity in early-RA patients with overweight and periodontal infection, whereby overweight and Porphyromonas gingivalis may enhance RA activity. This may represent a pathological mechanism between these conditions, where adipokines seem to have a key role.

Adipokine Profile on Joint and Periodontal Conditions in First-degree Relatives of Patients with Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by joint inflammation and destruction. OBJECTIVE: Establish the association between Porphyromonas gingivalis (P. gingivalis) infection, body mass index (BMI), joint involvement, and serum adipokines in first-degree relatives (FDR) of patients with rheumatoid arthritis (RA). METHODS: The cross-sectional study evaluated 124 FDR and 124 healthy controls (HC). The clinical examination included joint and radiographic evaluation and calculation of BMI. Serum adipokine levels were measured (leptin, vaspin, adiponectin, resistin, and adipsin), as were the erythrocyte sedimentation rate, C-reactive protein, and anti-citrullinated protein antibodies. Investigations were performed to detect P. gingivalis, and anti-P. gingivalis antibodies. Statistical analyses were performed to confirm associations. RESULTS: Leptin levels in FDR were associated with BMI >25 (OR, 2.64; 95%CI, 1.17-5.97; P=0.019), radiographic damage (Simple Erosion Narrowing Score [SENS])/hands, total SENS, and joint space narrowing in feet (P=0.037, 0.026, 0.020, respectively). FDR had more tender joints (P=0.018); this finding was associated with high levels of leptin and resistin and low levels of adipsin (P=0.040, 0.040, and 0.019, respectively). The presence of P. gingivalis was related to FDR, low levels of adipsin, resistin, adiponectin, and a trend toward higher levels of leptin (P=0.002, 0.001, 0.003, and 0.060, respectively), whereas anti-P. gingivalis antibodies were related to low levels of adipsin (P=0.001). CONCLUSION: In FDR, serum adipokine levels were associated with overweight and the presence of P. gingivalis. Adipokine levels were also associated with joint involvement. Hence, adipokines may be involved in the pathogenesis of RA in FDR and warrant further investigation.

Implementation of screening criteria for inflammatory bowel disease in patients with spondyloarthritis and its association with disease and endoscopic activity.

There is little literature on the implementation of screening criteria for inflammatory bowel disease (IBD) in patients with spondyloarthritis (SpA). This study aimed to apply IBD screening criteria in a group of patients with SpA without IBD diagnosis and correlate them to endoscopic findings and disease activity. A total of 82 patients with SpA were included. The IBD screening test and ileocolonoscopy with digital chromoendoscopy with magnification and histological analysis were performed. The data were analysed with Chi-square test/Fisher's exact test and multiple correspondence analysis. The major screening criteria found in 48.7% of the patients were associated with a history of infection (p = 0.037). Rectal bleeding was associated with the diagnosis of ankylosing spondylitis, acute inflammation, enthesitis and tissue architecture alteration in the ileum (p < 0.050). Diarrhoea was associated with a higher disease activity score (p = 0.02). Minor screening criteria were associated with painful inflammatory joint (p = 0.05), high disease activity score (p = 0.001) and high calprotectin levels (p = 0.050). Abdominal pain (36.9%) was associated with axial/peripheral compromise (p = 0.017), inflammatory back pain (p = 0.01), enthesitis (p = 0.021), higher disease activity score (p = 0.023) and acute ileum inflammation (p = 0.046). Diarrhoea of 4 weeks and abdominal pain were the most prevalent major and minor screening criteria, respectively, being related to early manifestations of inflammatory bowel compromise and higher disease activity score. This screening test grants a chance of opportune referral of SpA patients from rheumatology to gastroenterology.

Oral manifestations associated with inflammatory bowel disease and early endoscopic findings in patients with spondyloarthritis.

BACKGROUND AND AIMS: Spondyloarthritis (SpA) is a group of autoinflammatory disorders, of which the primary extra-articular manifestation is inflammatory bowel disease (IBD). The oral cavity being a part of gastrointestinal tract, is significantly compromised in IBD, and in many cases, it is the first site of clinical manifestations of IBD. This study aimed to identify changes in the oral mucosa associated with the onset of IBD and their association with endoscopic/histological findings. MATERIALS AND METHODS: The study assessed 80 patients with SpA and 52 healthy controls. Oral, rheumatological, and gastroenterological assessments were performed. The ileocolonoscopy was performed via digital magnification chromoendoscopy. The statistical analysis consisted of Chi-square, Fisher's exact, and multiple correspondence discriminant analysis tests. RESULTS: From the disease cohort, 63.0% patients showed oral lesions (p = 0.050). These manifestations ranged from gingivitis (55.0%, p = 0.001), aphthous stomatitis (3.8%, p = 0.091), angular cheilitis (2.6%, p = 0.200), and perioral erythema with scaling (1.3%, p = 0.300). All patients who presented with alterations in colonic mucosa also had oral lesions associated with IBD (p = 0.039), specifically gingivitis/aphthous stomatitis (p = 0.029). CONCLUSION: The patients with SpA without IBD present significant oral signs and symptoms. Gingivitis seems to be the most relevant because of its associations with early endoscopic and histological findings. CLINICAL RELEVANCE: An integral approach to the diagnostic tests that includes evaluations of oral, rheumatological and gastroenterological tissues may favor timely attention and improve patients' quality of life.

Association of Serum and Crevicular Fluid Dickkopf-1 Levels with Disease Activity and Periodontitis in Patients with Early Rheumatoid Arthritis.

BACKGROUND: The aim of this study was to assess DKK-1 levels, in Gingival Crevicular Fluid (GCF) and serum, as a biomarker for bone loss and disease activity in periodontitis and early RA (eRA). METHODS: In this cross-sectional study, we obtained serum and GCF from 10 interproximal sites (Distal Buccal I/S, Mesio Buccal I/S, Distal Palatal/Lingual, Mesio Palatal/Lingual) according to the highest degree of inflammation by a patient for 240 sites from eRA patients. Patients received a periodontal assessment, a radiographic evaluation, tomography of interproximal sites, and DKK1 levels were determined by ELISA. Comparisons were performed by the Mann-Whitney U test and analysis by Chi2 test, and a logistic regression model was applied. RESULTS: The mean age was 46.33 ± 12.0 years, the Disease Activity Score (DAS-28-ESR) was 4.08 ± 1.4. Periodontitis was present in 65.2% of the patients, and 59.6% of these patients had bone loss in interproximal sites. DISCUSSION: Higher GCF-DKK1 levels were associated with serum-DKK1 (OR:2.41 IC95% 1.14-5.09, p=0.021) and were related with DAS28-ESR (p=0.001), Routine Assessment of Patient Index Data 3 (RAPID 3) (p=0.001), and tender joints (p=0.040). Foot bone erosion and juxta-articular osteopenia were associated with high levels of serum-DKK1 (p=0.009 and 0.001, respectively). Serum-DKK1 were associated with SDAI (OR: 2.38 IC95% 1.03-5.52, p=0.043), RAPID 3 (p=0.001), and rheumatoid factor (p=0.018). The GCF-DKK1 levels were associated with periodontal bone loss (p=0.011), periodontitis (p=0.070) and its severity (OR: 2.58 IC95% 2.28-7.28, p=0.001). Bone loss was more frequent in buccal sites (73.5%) and was associated with increased levels of DKK1 (p=0.033). CONCLUSION: In the early stages of the eRA disease, serum and GCF-DKK1 could be a biomarker for clinical disease activity and periodontal and articular bone erosion.

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

BACKGROUND: 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.

Panorama mundial de las diferentes plataformas de vacunas contra el COVID-19: revisión y reflexión de la literatura actual / Worldwide Overview of the Different COVID-19 Vaccine Platforms: A Review and Reflection on the Current Evidence

RESUMEN Las vacunas son productos biológicos que contienen antígenos que buscan generar protección contra a la exposición real de un agente patógeno. En cuanto a su importancia, hacen parte de las intervenciones más costo-efectivas en salud pública, siendo superadas únicamente por el agua potable. A grandes rasgos, podemos dividir las vacunas en vivas atenuadas e inactivadas; no obstante, el nuevo coronavirus ha producido la emergencia de plataformas innovadoras que utilizan mecanismos intracelulares y moleculares con el mismo objetivo de generar inmunidad. Se realizó una búsqueda sistemática de la literatura utilizando las bases de datos electrónicas Pubmed, Scopus y Web of Science. Todos los tipos de diseño de estudio fueron considerados, sin embargo, se prefierieron aquellos redactados en idioma inglés o español. Se hace una revisión de la literatura presente sobre las plataformas existentes para generar inmunidad frente al coronavirus SARS-CoV-2 y se desarrolla cada una según su ruta y forma de acción en aquellas basadas en subunidades proteicas, vector viral recombinante, ácidos nucleicos, virus inactivados, partículas virales y virus vivos atenuados. Los mecanismos por los cuales dichas vacunas generan inmunogenicidad son diferentes, no obstante, la constante inserción de mutaciones por parte del virus sigue siendo un objeto de interés y preocupación por los investigadores.

ABSTRACT Vaccines are biological products containing antigens that aim to generate protection against real exposure to an infectious pathogen. They constitute the most cost-effective interventions in public health, being surpassed only by drinking water. Generally speaking, we can divide the vaccines into live attenuated and inactive; However, the new coronavirus has produced innovative platforms that use intracellular and molecular mechanisms with the same objective of generating immunity. A systematic literature search was carried out using the PUBMED, SCOPUS, and Web of Science electronic databases. All types of study design were selected, those written in English or Spanish were prioritized. We reviewed the existing platforms to generate immunity against the SARS-CoV-2 coronavirus. Each one is developed according to its route and form of action, and can be classified as protein subunits, recombinant viral vector, nucleic acids, inactivated viruses, viral particles, and live attenuated viruses. The mechanisms by which these vaccines generate immunogenicity are different; however, the constant insertion of mutations by the virus remains an object of interest and concern for researchers.

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.

P060 Screening Criteria of Inflammatory Bowel Disease: Application in Colombian Patients With Spondyloarthritis.

BACKGROUND: The Spondyloarthritis (SpA) is a group of chronic inflammatory rheumatic diseases, in which 5-10% of extra-articular manifestations are gastrointestinal such as the inflammatory bowel disease. Objective: To apply the clinical criteria for the screening of inflammatory bowel disease (IBD) in patients with SpA with gastrointestinal symptoms and its association with disease activity and function. METHODS: A Cross-sectional study included 82 patients with SpA, according to ASAS classification criteria without diagnosis of IBD. We applied the Screening criteria for IBD developed by Sanz et al, in the SpA patients. Clinical evaluation by rheumatologist and in patients with ≥ 2 gastrointestinal symptoms clinical evaluation by gastroenterologist and IBD screening criteria were performed. Digital chromoendoscopy, magnification colonoscopy, and histological analysis were performed. Lab tests included, C-reactive protein, sedimentation rate, serum levels of transferrin, ferritin and vitamin B12. The association between clinical variables and colonoscopy and histological variables were evaluated using the Chi-square or Fisher's exact test (Ethical / Cod. 2017-023). RESULTS: Of the 82 individuals evaluated, 58 of them were referred to gastroenterology with a direction to perform colonoscopy with chromeondospia, and 41 of them were able to intervene to whom the IBD screening criteria were applied. 53.7% are men, 7.3% actively smoke. 100% of the population presented some gastrointestinal symptoms, the most frequent being diarrhea of more than 4 weeks in 61%. 68.3% had at least one of the three major criteria. Rectorrhagia was associated with BASFI>4, p=0.050, axial compromise p = 0.043, diagnosis of PsA p = 0.090 and alterations in the architecture of the ileum p=0.034. Diarrhea was associated with ESR> 20, p = 0.050, BASFI>4 p = 0.012. In addition, 70.75 of the patients had at least one of the minor screening criteria associated with higher BASFI levels, p = 0.01. Aphthous stomatitis was reported as extra-intestinal manifestations in 7.3% and abdominal pain in 87.8% of the patients, which was associated with BASDAI>4 p = 0.023, ASDASCRP> 2.1, p = 0.043 and inflammation in the ileum, p = 0.046. No patients with positive iron deficiency anemia were found. However, ferritin alteration was observed in 22% associated with chronic inflammation of the colon, p = 0.042. There were no cases of fever or family history of IBD. Noting that in 17.1% of the cases a decrease in vitamin B12 levels was detected, associated with the presence of ulcers (p = 0.035) and acute inflammation in the ileum, p = 0.032. Weight loss was found in 31.7% of the cases and was associated with smoking history p = 0.039. CONCLUSION: We found a high frequency of major and minor symptoms of IBD, both of which were associated with a high activity of spondyloarthritis and an important functional compromise as well as inflammation markers in this group of patients. The application of the screening criteria for IBD in SpA without IBD reflects a high frequency of intestinal symptoms of sufficient intensity that affect quality of life and disease activity. Early detection of gastrointestinal compromise allows patients to benefit from comprehensive treatment of the disease in its initial stages.

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.

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

OBJECTIVE: 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.

Use of nutritional food labels and consumers confidence in label information / Uso da rotulagem nutricional e percepção sobre a confiabilidade das informações por consumidores

ABSTRACT Objective This investigation evaluated the use of food labels and consumers' perception of the reliability of food labels nutritional information. Methods This is a transversal exploratory quantitative investigation, carried out in Curitiba, Brazil. A total of 536 students from a public institution participated in the survey answering a structured questionnaire. Descriptive analyses, Chi-Square test and Fisher's exact test were performed considering a significance level of 5%. Results The participants' mean age was 21.11±2.83 years, and 59.3% were female. It was noticed that 41.6% of consumers used the nutritional information sometimes and 14.7% always, mainly because they liked to know what they were buying and consuming (35.8%). Lack of patience (29.5%) and concern about the composition of the food purchased (34.2%) were the main reasons for not using the information provided. The most commonly used nutrition claim was "trans fat-free" (42.5%) and the type of food in which nutrition labeling was used most was milk and dairy products (42.0%). Frequent use of nutritional information was higher among women (p<0.01) and among those who practice physical activity (p=0.04). Many individuals relied on food labels nutritional information (61.9%), but out of these, 43.6% did not use that information at the time of purchase. There was no difference between respondents' confidence in the information, sociodemographic and health data. Conclusion Many people still do not use the label nutrition information. Efforts should be made to change this scenario. Changes in nutrition labeling can help modify this situation, with the use of clearer label information, more easily understood, that does not raise any doubts in the consumers' mind.

RESUMO Objetivo Este estudo avaliou o uso da rotulagem nutricional e a percepção sobre a confiabilidade das informações por consumidores. Métodos Pesquisa transversal, exploratória e de abordagem quantitativa, realizada no município de Curitiba, Brasil. Participaram 536 estudantes, de uma instituição pública, respondendo um questionário estruturado. Foram realizadas análises descritivas, teste Qui-Quadrado e teste exato de Fisher, considerando nível de significância de 5%. Resultados A idade média dos participantes foi 21,11±2,83 anos, sendo 59,3% do sexo feminino. Quanto ao uso das informações nutricionais, 41,6% utilizavam às vezes e 14,7% sempre, principalmente porque gostavam de saber o que estavam comprando e consumindo (35,8%). A falta de paciência (29,5%) e de preocupação com a composição do alimento comprado (34,2%) foram os principais motivos pelos quais não utilizarem as informações. A alegação nutricional mais utilizada foi "sem gordura trans" (42,5%) e o tipo de alimento em que mais se utilizou a rotulagem nutricional foi leite e derivados (42,0%). O uso frequente das informações nutricionais foi maior entre as mulheres (p<0,01) e os praticantes de atividade física (p=0,04). Muitos indivíduos confiavam nas informações presentes nos rótulos dos alimentos (61,9%), porém, destes, 43,6% não as utilizavam no momento da compra. Não foram observadas diferenças entre a confiança das informações, os dados sociodemográficos ou de saúde dos entrevistados. Conclusão Muitas pessoas ainda não usam as informações nutricionais, sendo necessário esforços para mudar este panorama. Alterações na rotulagem nutricional podem mudar este processo, com o uso de informações mais claras, de fácil entendimento, que não gerem dúvida ao consumidor.

Predictive factors related to the progression of periodontal disease in patients with early rheumatoid arthritis: a cohort study.

BACKGROUND: Rheumatoid arthritis (RA) and periodontal disease are inter-related conditions. However, factors predictive of periodontal disease progression in patients with early rheumatoid arthritis (eRA) are lacking. The aim of this study was to identify factors associated with the progression of clinical attachment loss (CAL) in interproximal dental sites of eRA patients. METHODS: Twenty-eight eRA patients were evaluated for the progression of CAL at 280 interproximal dental sites at 1 year of follow-up. Markers of RA activity (rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein), a marker of bone resorption (Dickkopf-related protein 1), Disease Activity Score 28 and Simple Disease Activity Index were included as potential systemic predictive factors. Plaque index, gingival index, pocket depth, clinical attachment level and Dickkopf-related protein 1 in crevicular fluid at baseline were included as potential local predictive factors. Data were analysed in a hierarchical structure using generalised linear mixed models for progression at each site (> 2 mm) during follow-up. RESULTS: C-reactive protein level was the most important predictive systemic factor for the progression of CAL. The mean CAL and a high degree of gingival inflammation in interproximal sites at baseline were important predictive local factors (p <  0.0001). Patients who received combined treatment with disease-modifying antirheumatic drugs and corticosteroids exhibited less CAL (p <  0.0001). The predictive value of the generalised linear mixed model for progression was 85%. CONCLUSIONS: Systemic factors, including RA disease activity and baseline periodontal condition, were associated with periodontal progression. Pharmacological treatment may affect periodontal progression in patients with early RA.

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.

Autoantibodies and Gastrointestinal Symptoms in Colombian Children with Juvenile Idiopathic Arthritis.

BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is the most common inflammatory joint disease in children. JIA and autoimmune inflammatory Gastrointestinal (GI) diseases share common etiologic mechanisms, including genetic predisposition and environmental influences. OBJECTIVE: To Investigate association between gastrointestinal, rheumatologic clinical variables and the presence of autoantibodies in patients with JIA in treatment. METHODOLOGY: In a cross-sectional study of patients with JIA according to diagnostic criteria and the ILAR classification. GI symptoms and autoantibody expression were evaluated with respect to their association with JIA clinical variables. Anti-Saccharomyces Cerevisiae IgG/IgA (ASCA), 6 antigen associated with anti polymorphonuclear neutrophil (ANCA), anti Transglutaminase (tTG) IgG/IgA, anti deaminated gliadin peptide (DGP) IgG/IgA autoantibodies, ANAS and IgA were measured in all patients. The association between clinical variables and auto-antibodies were evaluated using the Fisher test with significant value of p <0.05. The study was approved by the ethics committee of the all institutions. RESULTS: Samples were collected from ninety-seven patients, 63% of whom were female. The average age was 14 years. The JIA subtype associated with the most common GI symptoms was enthesitis- related arthritis. Of these patients, 44.3% and 14% reported abdominal pain and diarrhea, respectively. Anti-DPG and anti-tTG antibodies were found in 9.28% and 7.22%, respectively and 11.34% were positive for p-ANCA, and 2% were positive for ASCA. CONCLUSION: GI symptoms and autoantibodies associated with inflammation of the GI mucosa were detected in JIA patients but were not associated with autoantibodies or clinical variables. However, it is the monitoring of these patients diagnosis is important.

The Frequency of HLA-B27 in a Colombian Population with Signs of Spondyloarthritis.

BACKGROUND: 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.

Higher Levels of Secretory IgA Are Associated with Low Disease Activity Index in Patients with Reactive Arthritis and Undifferentiated Spondyloarthritis.

INTRODUCTION: Both reactive arthritis (ReA) and undifferentiated spondyloarthritis (uSpA) belong to the group of autoinflammatory diseases called spondyloarthritis (SpA). Hypotheses have been proposed about a relationship between the intestinal mucosa and inflammation of joint tissues. The role of immunoglobulin IgA or secretory immunoglobulin A (SIgA) in the inflammatory and/or clinical activity of patients with SpA remains poorly understood. OBJECTIVE: To evaluate the status of total IgA and SIgA, and the association among the levels of SIgA, IgA, IgA anti-Chlamydia trachomatis, and anti-Shigella spp. with the disease activity measures, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, was compared in a cohort of patients with ReA and uSpA and healthy subjects. METHODS: This was a cross-sectional study. The serum concentrations of SIgA, IgA anti-C. trachomatis, anti-Shigella spp., and total IgA were measured. Disease activity was measured in each patient by means of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS). Statistical analysis did include as bivariate evaluation, comparisons by Student's t-test, Kruskal-Wallis test, and U Mann-Whitney test, with a multivariate evaluation by principal components analysis (PCA). A correlation analysis was carried out using the Pearson correlation coefficient and a linear regression models. All analysis were made using Stata version 11.2® for Windows, R V3.3.21. Statistical significance was defined a p-value <0.05. RESULTS: In all, 46 patients (78.2% men; mean age, 34.8 ± 12.3 years) and 53 controls (41% men; mean age, 32 ± 11.4 years) were included in the study. The mean serum levels of SIgA were higher in SpA patients than in healthy subjects (p < 0.001). Only SIgA levels correlated with disease activity: BASDAI (r = -0.42, p = 0.0046), ASDAS-CRP (r = -0.37, p = 0.014), and ASDAS-ESR (r = -0.45, p = 0.0021). The negative correlation between SIgA and all activity indices was higher in HLA-B27-positive patients (BASDAI r = -0.70, p = 0.0009, ASDAS-CRP r = -0.58, p = 0.0093, and ASDAS-ESR r = -0.57, p = 0.0083). The PCA showed three factors: the first component was constituted by variables referred as clinical activity measures, the second did include the serological activity markers, and the last component was compounded by age and symptoms time. CONCLUSION: Elevated serum levels of SIgA were found to be related with low disease activity in patients with ReA and uSpA.