Low Frequency of Upper Gastrointestinal Bleeding Despite Non-Steroidal Anti-Inflammatory Drugs and Corticosteroids in Patients with Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease. It has been identified that non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids can be essential risk factors for developing complications such as upper gastrointestinal bleeding (UGIB). OBJECTIVE: This study aimed to describe the safety profile of drugs used to treat RA focused in UGIB. METHODS: A cross-sectional study of patients with RA between 2015 and 2021, a description of the population, and an evaluation of the relationship with UGIB through bivariate analysis and logistic regression. RESULTS: Of 405 individuals, 16 presented UGIB (93.8% women, mean age was 65±13.6 years). No statistically significant differences were found regarding UGIB and medication use, except for the mean dose of corticosteroids. In the multivariate analysis, it was found that the presence of anemia in the last three months had an adjusted OR (ORA) of 16.1 (95% CI 2.74- 24.23) and higher HAQ values during the previous three months had an ORA of 6.17 (95% CI 1.79- 21.24). CONCLUSION: This study found a low frequency of UGIB in patients with RA. More significant disability and anemia in the previous months were independently associated with UGIB. The low frequency of NSAID use in this population is noteworthy. In general, reasonable medication use related to this complication is recommended.

Differential gut microbiome in spondyloarthritis patients associated to Blastocystis colonization.

The role of Blastocystis in intestinal health is an open controversy, and little is known about the potential effect of this microorganism in autoinflammatory diseases such as spondyloarthritis (SpA). Here, we analyzed the gut microbiome of 36 SpA patients and 13 control individuals and demonstrated that the richness, diversity, and taxonomic composition between these two groups are different. We also showed that colonization by Blastocystis in control individuals increases the richness and diversity of the intestinal microbiome, whereas in SpA patients, it does not seem to have any impact. This may reflect a potential role of Blastocystis in sculpting the gut microbiome architecture in control individuals, whereas in subjects with SpA, the modulation of the microbiome may be governed by disease-dependent factors that cannot be overcome by Blastocystis. Regarding taxonomic characterization, SpA patients colonized by Blastocystis showed significant increases in the phylum Pseudomonadota, class Gammaproteobacteria, family Succinivibrionaceae, and genus Succinivibrio. Simultaneously, there were significant increases in the class Bacilli, order Lactobacillales, families Lactobacillaceae and Clostridiaceae, and genera Lactobacillus and Clostridium in non-colonized SpA patients. On the other hand, PICRUSt analysis in Blastocystis-positive SpA patients showed elevations in pathways that may enhance antioxidant capacities and alleviate intestinal inflammation, while Blastocystis-negative SpA patients showed significant changes in pathways that promote cell division/proliferation and can lead to larger changes in the gut microbiome. Our analyses lead us to believe that these changes in the gut microbiome of SpA patients may trigger protective mechanisms as an initial response to inflammation in an attempt to restore balance in the intestinal environment.

Posttranslational modifications in psoriatic arthritis: A systematic literature review.

BACKGROUND AND AIMS: Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The aim of this systematic review was to collect all published evidence regarding posttranslational modifications in PsA, and the main outcome was to evaluate an association between disease outcomes and specific posttranslational modifications in PsA. METHODS: A systematic electronic search was performed in Medline, PubMed, Cochrane, Virtual Health Library, and Embase databases. A total of 587 articles were identified; 59 were evaluated after removing duplicates and scanning, of which 47 were included. A descriptive analysis was conducted, with results grouped according to the type of posttranslational modification evaluated. The protocol was registered at the PROSPERO database. RESULTS: Seven posttranslational modifications were identified: citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress. Anti-citrullinated peptide and anti-carbamylated protein have been evaluated in rheumatoid arthritis. There is now information suggesting that these antibodies may be helpful in improving the diagnosis of PsA and that they may demonstrate a correlation with worse disease progression (erosions, polyarticular involvement, and poor treatment response). Glycosylation was associated with increased inflammation and phosphorylation products related to the expression of SIRT2 and pSTAT3 or the presence of Th17 and cytokine interleukin-22, suggesting a possible therapeutic target. CONCLUSIONS: Posttranslational modifications often play a key role in modulating protein function in PsA and correlate with disease outcomes. Citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress were identified as associated with diagnosis and prognosis.

Chronic inflammatory demyelinating polyradiculoneuropathy in a patient with systemic lupus erythematosus without systemic activity.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an uncommon subtype of peripheral neuropathy, especially in systemic lupus erythematosus (SLE). We report a case of SLE presenting with CIDP successfully treated. The patient presented with bilateral, progressive, ascending, sensory, and motor neuropathy. Electrodiagnostic tests reported active motor and sensitive demyelinating polyneuropathy, and the diagnosis of CIDP was confirmed according to the European Federation of Neurological Societies/Peripheral Nerve Society criteria. Initial management with intravenous immunoglobulin and high-dose steroids was administered, then 6-month intravenous cyclophosphamide was initiated with improvement according to clinical scales. In conclusion, CIDP in SLE is rare, reported in just 0.2%. Immunosuppressive therapy should be considered whether initial improvement is not evidenced, as seen in our case requiring cyclophosphamide; interestingly, systemic activity was in remission as the peripheral nervous system is not part of neurological compromise, and we suggest evaluating this unusual presentation into rheumatological practice.

The Interaction Effect of Anti-RgpA and Anti-PPAD Antibody Titers: An Indicator for Rheumatoid Arthritis Diagnosis.

Porphyromonas gingivalis secretes virulence factors like Arg-gingipains and peptidyl arginine deiminase (PPAD), that are associated with rheumatoid arthritis (RA) pathogenesis. However, there is no information regarding the antibody titers for these bacterial enzymes as systemic indicators or biomarkers in RA. In this cross-sectional study, 255 individuals were evaluated: 143 were diagnosed with RA, and 112 were without RA. Logistic regression models adjusted for age, sex, basal metabolic index, smoking, and periodontitis severity were used to evaluate the association of RA with rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs), erythrocyte sedimentation rate, high sensitivity C-reactive protein, anti-RgpA, anti-PPAD, and double positive anti-RgpA/anti-PPAD. It was found that RF (odds ratio [OR] 10.6; 95% confidence interval [CI] 4.4-25), ACPAs (OR 13.7; 95% CI 5.1-35), and anti-RgpA/anti-PPAD double positivity (OR 6.63; 95% CI 1.61-27) were associated with RA diagnoses. Anti-RgpA was also associated with RA (OR 4.09; 95% CI 1.2-13.9). The combination of anti-RgpA/anti-PPAD showed a high specificity of 93.7% and 82.5% PPV in identifying individuals with RA. RgpA antibodies were associated with the periodontal inflammatory index in RA individuals (p < 0.05). The double positivity of the anti-RgpA/anti-PPAD antibodies enhanced the diagnosis of RA. Therefore, RgpA antibodies and anti-RgpA/anti-PPAD may be biomarkers for RA.

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.

Analysis of Ana/Dfs70 Pattern in a Large Cohort of Autoimmune/Autoinflammatory Diseases Compared with First Degree Relatives and Healthy Controls Evaluated from Colombia.

BACKGROUND: The presence of Antinuclear antibodies/Dense Fine Speckled 70 (ANA/DFS70) has been proposed as a negative biomarker in the process of exclusion of systemic autoimmune/autoinflammatory rheumatic diseases (SARD). The purpose was to evaluate and characterize ANA/DFS70 patients in a large Colombian population with SARD; rheumatoid arthritis (RA), Psoriasis (PsO), Undifferentiated connective tissue disease (UCTD), first-degree relatives of (FDR), and healthy controls (HC). METHODS: ANA determination was performed using indirect immunofluorescence. Samples with positive dense fine granular staining in the nucleoplasm of the interphase cell (AC2) fluorescence were confirmed with CytoBead/ANA and ANA/modified (Knocked out for the PSPI1 gen). RESULTS: 530 mestizo Colombian participants were included. ANA/DFS70 antibody positivity in the whole group was 2.3%, and 0.8% in SARD; no RA patients were positive. ANA/DFS70 positives in UCTD were three women; the average time of evolution of the disease was 9.4 years. The most frequent clinical findings were arthralgias, non-erosive arthritis, and Raynaud's phenomenon. The PsO positive was a woman with C-reactive protein (CRP) positivity and a negative erythrocyte sedimentation rate (ESR) without any other positive autoantibody or extracutaneous manifestation. FDR and HC positives were 7/8 women. All were negative for other autoantibodies. CONCLUSIONS: ANA/DFS70 autoantibodies were present in Colombian patients with SARD at a shallow frequency, they were more prevalent in healthy individuals.

Decreased fecal calprotectin levels in Spondyloarthritis patients colonized by Blastocystis spp.

Spondyloarthritis (SpA) is a group of chronic inflammatory systemic diseases mainly characterized by inflammation in the spine and/or peripheral joints. Although a link between SpA-pathogenesis, intestinal inflammation and gut dysbiosis has been proposed, studies have been focused on bacteria-host interactions and very little has been reported regarding intestinal parasites. Here, intestinal parasitic infection of 51 SpA-patients were evaluated and compared to healthy control individuals. No significant differences in the frequency of any parasite between SpA-patients and control individuals were found. Significantly higher levels of fecal calprotectin (FCP) were found in the SpA-patients compared to the control individuals. However, FCP levels were the same when comparing SpA-patients and control individuals, both colonized by Blastocystis spp. On the other hand, when comparing Blastocystis spp. colonized and Blastocystis spp. free SpA-patients, FCP levels were significantly higher in those Blastocystis spp. free. Without ignoring the small sample size as a study limitation, the results showed that in the SpA-patients colonized by Blastocystis spp., the FCP levels were significantly lower than those in the Blastocystis spp. free group and comparable to those in the control group. These findings seem to suggest a relationship between Blastocystis spp. and intestinal inflammation in SpA-patients, but studies intended to explore that interaction specifically should be designed.

Infection detection in patients with systemic lupus erythematosus using a hospital administrative database

Objective: To estimate the frequency of infections and to describe the pattern of these infections among patients diagnosed with Systemic Lupus Erythematous (SLE) treated at the Central Military Hospital (HOMIL). Methods: A descriptive study was carried out using an administrative database of the military hospital, we used a validated algorithm that classifies patients as having SLE in administrative databases. Infection was defined as an event with main diagnosis using the International Statistical Classification of Diseases and Related Health Problems (ICD-10) coding algorithm or by searching the antibiotics prescription database, additionally, we abstracted some variables related to SLE status in the group of patients in whom infections were documented during the infection event. Results: 237 SLE patients were identified. The mean age was 41.9 years (CI 29.0-54.3), 80% were female, 97.7% used conventional disease-modifying anti-rheumatic drugs (DMARDs). Of these 237 patients, 22 (9.4%) met the operative definition of infection, in this group the mean age was 44.3 years (SD 16.4). All the 22 patients received conventional DMARDs and none of them had concomitant biologic therapy. In this group of patients, the most common type of infection was bacterial (72.7%), followed by viral (9.1%) including a patient with SARS-CoV-2 infection. Conclusion: Hospital administrative databases can be a useful source of information for monitoring outcomes that generate significant morbidity and mortality in patients with SLE, in the group of patients in whom infections were documented, bacterial infections were the most frequent. The most documented clinical findings were leukopenia, systemic steroid therapy, and concomitant disease activity.

Objetivo: Estimar la frecuencia de las infecciones y describir su patrón de presentación en pacientes con diagnóstico de lupus eritematoso sistémico (LES) atendidos en el Hospital Militar Central (Homil) en Bogotá, Colombia. Métodos: Se realizó un estudio descriptivo en el que se utilizó una base de datos administrativa del Hospital Military se empleó un algoritmo validado que clasificó a los pacientes con LES en las bases de datos administrativas. La infección se definió a partir de los códigos CIE-10 o por la búsqueda en la base de datos de la prescripción de antibióticos; adicionalmente, en las historias clínicas del grupo de pacientes en los que se documentaron infecciones, se revisaron algunas variables relacionadas con el estado de LES durante el evento de la infección. Resultados: Se identificaron 237 pacientes con LES, cuya edad media fue de 41,9 años (IC 29,0-54.3), el 80% eran mujeres y el 97,7% usaba medicamentos antirreumáticos modificadores de la enfermedad (DMARD) convencionales. De estos 237 pacientes, 22 (9,4%) cumplieron con la definición operativa de infección; en este grupo la edad media fue de 44,3 anos (DE = 16.4). Los 22 pacientes recibieron DMARD convencionales y ninguno recibió terapia biológica concomitante. En este grupo, el tipo de infección más común fue la bacteriana (72,7%), seguida de la viral (9,1%), incluido un paciente con infección por SARS-CoV-2. Conclusiones: Las bases de datos administrativas hospitalarias pueden ser una fuente útil de información para el seguimiento de los eventos que generan una morbimortalidad significativa en los pacientes con LES. En el grupo de pacientes en los que se documentaron infecciones, las infecciones bacterianas fueron las más frecuentes y los hallazgos clínicos más comúnmente documentados fueron la leucopenia, la terapia con esteroides sistémicos y la actividad de la enfermedad concomitante.

Evaluation of the adipokine profile (adiponectin, resistin, adipsin, vaspin, and leptin) in patients with early rheumatoid arthritis and its correlation with disease activity.

Introduction: Adipokines may play a role in the early stages of rheumatoid arthritis. This study evaluated the performance of adipokines in a Colombian population with early rheumatoid arthritis and its relationship with disease activity. Material and methods: A cross-sectional study evaluated serum adipokine levels (adiponectin, resistin, adipsin, vaspin, and leptin) in patients with early rheumatoid arthritis (eRA), evaluating demographic and clinical variables, along with a control group matched by age and gender. A factorial analysis was performed using principal components analysis (PCA), and a Spearman correlation analysis was performed. Similarly, a cut-off point for serum levels is proposed based on the receiver operating characteristic (ROC) curve between eRA and controls and sensitivity analysis. Results: Fifty-one eRA subjects were included; there were 41 women. The body mass index (BMI) was 25.12 ±3.8. A statistically significant correlation was identified between adipsin, BMI, and RAPID3. Vaspin and leptin were correlated with BMI. Resistin levels were higher in patients with RAPID3 near remission (p = 0.041), and adiponectin, vaspin, and leptin levels were lower in patients with DAS28 ESR in remission (p = 0.033, p = 0.012, and p = 0.017, respectively). Principal components analysis in component 1 adipokines as adipsin and leptin with BMI and RAPID3 as disease activity index are grouped. Moreover, component 2 had a strong relation between ESR and CRP with an inverse correlation with cholesterol levels and vaspin. A cut-off point was established for each adipokine, thus identifying the best performance for leptin levels greater than 0.58 ng/ml with a sensitivity of 76.5% and specificity of 74.5%. Conclusions: Adipokine levels are relevant in eRA, especially with disease activity indexes. Resistin levels were higher in patients with an activity index near remission. Otherwise, adiponectin, vaspin, and leptin levels were lower in patients with low activity indexes. RAPID3 correlated with adipsin. It is complementary to the previously published analysis of adipokines.

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.

Increasing of SIgA serum levels may reflect subclinical intestinal involvement in non-radiographic axial and peripheral spondyloarthritis.

OBJECTIVE: The evidence shows that previous infection with enteric pathogens is a requirement to develop pSpA. Based on our previous results, variances on regulation of SIgA might influence SpA activity; thus, the aim of this study was to correlate the levels of SIgA, IgA against some enteric bacteria, and IL-17, IL-21, and IL-6 with clinical features in a group of SpA patients. METHODS: Twenty-six pSpA, 20 nr-axSpA, 60 healthy volunteers (HV), and 34 patients with inflammatory bowel diseases (IBD) were included. All subjects were assessed to measure SIgA, total and specific IgA for enteric bacteria, and IL-17, IL-21, and IL-6 levels and clinical variables. For SpA patients, the diagnosis was verified 5 years after first evaluation to assess the risk of developing r-axSpA. RESULTS: SIgA levels were significantly higher in SpA patients than in HV and IBD (p < 0.0001 and p = 0.047, respectively). However, no differences for SIgA neither total IgA were found among the SpA subtypes (p = 0.624). Only IL-6 was higher in SpA than HV (p = 0.013). An inverse correlation was demonstrated for SIgA and BASFI (r: - 0.45; p = 0.003), BASDAI (r: - 0.39; p = 0.0123), ASDAS-CRP (r: - 0.37; p = 0.014), and ASDAS-ESR (r: - 0.45; p = 0.0021). There was no evidence of risk of developing r-axSpA in patients who previously showed high levels of serum antibodies. CONCLUSION: The results show that pSpA as well as nr-axSpA share a similar SIgA-intestinal involvement independently of a previous infection. This suggests that serum SIgA increases are evidence of subclinical intestinal compromise which could have influence on disease activity but not in this progression. Key Point • The levels of SIgA, IgA against some enteric bacteria, and IL-17, IL-21, and IL-6 are correlated with clinical features in a group of SpA patients.

Design of an algorithm for the diagnostic approach of patients with joint pain.

BACKGROUND: Rheumatic diseases are a reason for frequent consultation with primary care doctors. Unfortunately, there is a high percentage of misdiagnosis. OBJECTIVE: To design an algorithm to be used by primary care physicians to improve the diagnostic approach of the patient with joint pain, and thus improve the diagnostic capacity in four rheumatic diseases. METHODS: Based on the information obtained from a literature review, we identified the main symptoms, signs, and paraclinical tests related to the diagnosis of rheumatoid arthritis, spondyloarthritis with peripheral involvement, systemic lupus erythematosus with joint involvement, and osteoarthritis. We conducted 3 consultations with a group of expert rheumatologists, using the Delphi technique, to design a diagnostic algorithm that has as a starting point "joint pain" as a common symptom for the four diseases. RESULTS: Thirty-nine rheumatologists from 18 countries of Ibero-America participated in the Delphi exercise. In the first consultation, we presented 94 items to the experts (35 symptoms, 31 signs, and 28 paraclinical tests) candidates to be part of the algorithm; 74 items (25 symptoms, 27 signs, and 22 paraclinical tests) were chosen. In the second consultation, the decision nodes of the algorithm were chosen, and in the third, its final structure was defined. The Delphi exercise lasted 8 months; 100% of the experts participated in the three consultations. CONCLUSION: We present an algorithm designed through an international consensus of experts, in which Delphi methodology was used, to support primary care physicians in the clinical approach to patients with joint pain. Key Points • We developed an algorithm with the participation of rheumatologists from 18 countries of Ibero-America, which gives a global vision of the clinical context of the patient with joint pain. • We integrated four rheumatic diseases into one tool with one common symptom: joint pain. It is a novel tool, as it is the first algorithm that will support the primary care physician in the consideration of four different rheumatic diseases. • It will improve the correct diagnosis and reduce the number of paraclinical tests requested by primary care physicians, in the management of patients with joint pain. This point was verified in a recently published study in the journal Rheumatology International (reference number 31).

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.

Frecuencia de ANCA positivos en una población con síntomas clínicos sugestivos de enfermedad autoinmune y la interferencia de ANA en su interpretación / Frequency of positive ANCA test in a population with clinical symptoms suggestive of autoimmune disease and the interference of ANA in its interpretation

ANTECEDENTES: Los anticuerpos anticitoplasma del neutrófilo (ANCA) se asocian con vasculitis. Existen diferentes métodos para determinar su presencia. Se ha descrito la interferencia de anticuerpos antinucleares (ANA) en la diferenciación de los patrones P-ANCA y C-ANCA. OBJETIVO: Determinar la frecuencia de ANCA en una población con manifestaciones de enfermedad autoinmune; y evaluar la interferencia de los ANA en su interpretación. MATERIALES Y MÉTODOS: Estudio de corte transversal retrospectivo, descriptivo no experimental incluyendo 3.330 datos con diagnóstico presuntivo de enfermedad autoinmune y solicitud de ANCA. Las determinaciones de ANCA y de ANA se realizaron mediante inmunofluorescencia indirecta, L-ANCA® y CytoBead® ANCA. Antiproteinasa 3 y antimieloperoxidasa fueron determinados mediante ELISA y CytoBead® ANCA. RESULTADOS: Se encontraron ANCA positivos en el 10,21% y el 12,64% con ANCA positivos presentaban ANA positivos. La concordancia kappa para antiproteinasa 3 entre CytoBead® ANCA y ELISA fue del 100% (K=1; p < 0,05), La concordancia entre antimieloperoxidasa por ELISA y CytoBead®ANCA fue alta (K=0,94; p < 0,05). El 30% de aquellos con ANCA positivos tenía diagnóstico de algún tipo de vasculitis, el 20% cursaba con alguna enfermedad autoinmune. CONCLUSIONES: Los resultados indican una solicitud sobreestimada de este marcador como ayuda diagnóstica en consulta de atención primaria no direccionada. Para una adecuada evaluación de ANCA se debe implementar la técnica de inmunofluorescencia indirecta para tamizaje y confirmar con la determinación de antígenos específicos para antiproteinasa 3 y antimieloperoxidasa por cualquiera de los ensayos confirmatorios. La alta concordancia mostrada por CytoBeads® ANCA hace que planteemos el empleo de dicha alternativa para la determinación de ANCA y su confirmación. Dada la interferencia de los ANA, se recomienda solicitar la prueba ANA por inmunofluorescencia indirecta ante la presencia de resultados P-ANCA positivos, con el fin de minimizar «falsos positivos»

BACKGROUND: Antibodies against neutrophil cytoplasm (ANCA) are associated with vasculitis. There are different methods to determine their presence. The interference of antinuclear antibodies (ANA) in the differentiation between P-ANCA and C-ANCA patterns has been described. OBJECTIVE: To determine the frequency of ANCA in a population with manifestations of autoimmune disease, and evaluate the interference of ANA in its interpretation. MATERIALS AND METHODS: Retrospective, descriptive nonexperimental cross-sectional study, including 3,330 data. The presumptive diagnosis was autoimmune disease and a test for ANCA was requested. The ANCA and ANA determinations were made by indirect immunofluorescence, L-ANCA® and CytoBead® ANCA. Anti-proteinase 3 and anti-myeloperoxidase were detected by ELISA and CytoBead® ANCA. RESULTS: ANCAs were positive in 10.21% and 12.64% of those positive for ANCA were positive for ANA. The inter-rater agreement statistic (Kappa) for anti-PR3 between CytoBead ANCA and ELISA was 100% (K=1.00; P<.05) and the agreement between anti- myeloperoxidase by ELISA and CytoBead® ANCA was high (K=0.94; P<.05). 30% of those with ANCAs had a diagnosis of a type of vasculitis; 20% of them had an autoimmune disease. CONCLUSIONS: The results suggest an overestimated request for ANCAs as a diagnostic aid in primary care which was not addressed. For an adequate evaluation of ANCAs, the indirect immunofluorescence technique should be implemented for the control and confirmation with the determination of specific antigens for anti- proteinase 3 and anti- myeloperoxidase in any of the confirmatory assays. The high concordance shown by ANCA CytoBeads makes us consider the use of this alternative for the determination of ANCAs and the confirmation. Given the interference of ANAs, the ANA test by IFI in the presence of positive P-ANCA results is recommended in order to minimize "false positives"

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.