[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.

[HLA alleles heterogeneity in a sample of colombian patients with a diagnosis of psoriatic arthritis]. / Heterogeneidad de alelos HLA, en una muestra de pacientes con diagnóstico de artritis psoriásica en Colombia.

OBJECTIVE: The objective is to describe the HLA allelic frequency in PsA and correlate it with demographic and clinical variables. METHODS: Retrospective study of adult patients with a diagnosis of PsA (n=23) and healthy controls (n=46), all with a request for HLA-A, B, C, DR. Typing was performed using HLA-PCR/SSO LifeCodes and analyzed on the LUMINEX IS100/200 xMAP® system. (Ethics/Code HMC2022-014). RESULTS: One hundred thirty-eight alleles were included from 69 individuals, 43,5% women, aged 44,5±16,5 years in patients with PsA, with a mean age of disease onset of 33.4±14 years. Only 9.5% had a high Body Mass Index and dyslipidemia was the most frequent comorbidity (34.8%), followed by high blood pressure (26,1%). 82% debuted with skin manifestation and once the joint disease was established, the predominance was peripheral (74%) due to arthritis/arthralgia in 74%, enthesitis in 30% and dactylitis in 13%. The allele frequencies were for HLA*A 2402 (13%), 3201 (13%) and 2427 (8,7%), for HLA*B 1402 (17,4%), 4002 (17,4%), 3801 (13%) and HLA*DR 0404 (17,4%), 0407 (13%). No HLA*B27 was identified and HLA*C0602 was only 2,2%. HLA A*0201 and DR*1301 were less frequent in controls versus PsA (p=0.024 and 0,029, respectively), while HLA*B1302 was frequent in PsA (p=0,035). CONCLUSIONS: Curiously, there were no positive results for HLAB*27, which may be related to the population mix. HLA Cw6 is traditionally associated with psoriasis. However, its absence has been linked to nail disorders and PsA; consequently, in our study, it had a low frequency (2,2%). On the other hand, HLA*B1302 has been related to the disease and its early onset; in the healthy Colombian population, it has been described in 0,92%; in our group, it is found to be significant in patients without establishing a clinical association. Few previous studies report HLA results in PsA in Colombia.

OBJETIVO: Describir la frecuencia alélica de HLA en APs y asociarlo con variables demográficas y clínicas. MÉTODOS: Estudio retrospectivo de pacientes adultos con diagnóstico de APs (n=23), y controles sanos (n=46), todos con solicitud de HLA-A, B, C y DR. La tipificación se realizó por medio de HLA-PCR/SSO LifeCodes, y se analizó en el sistema LUMINEX IS 100/200 xMAP®. (Ética/Código HMC2022-014). RESULTADOS: Se incluyeron 138 alelos de 69 individuos, 43,5% mujeres, con edad 44,5±16,5 años, en pacientes con APs, con edad media de inicio de la enfermedad de 33,4±14 años. Solo el 9,5% tuvo Índice de Masa Corporal alto y la dislipidemia fue la comorbilidad más frecuente (34,8%), seguida de hipertensión arterial (26,1%). El 82% debutó con manifestación en piel y una vez establecida la enfermedad articular, el predominio fue periférico (74%), por artritis/artralgias en un 74%, entesitis en 30%, y dactilitis 13%. Las frecuencias alélicas fueron para HLA*A 2402 (13%), 3201 (13%) y 2427 (8,7%), para HLA*B 1402 (17,4%), 4002 (17,4%), 3801 (13%) y HLA*DR 0404 (17,4%), 0407 (13%). No se identificó HLA*B27 y HLA*C0602 fue solo del 2,2 %. HLA A*0201 y DR*1301 fueron menos frecuentes en controles versus APs (p=0,024 y 0,029, respectivamente), mientras que HLA*B1302 frecuente en APs (p=0,035). CONCLUSIÓN: Curiosamente no hubo resultados positivos para HLAB*27 y esto puede relacionarse con el mestizaje de la población. HLA Cw6 es tradicionalmente asociado a psoriasis, sin embargo, su ausencia se ha relacionado con mayor reporte de alteraciones ungueales y Aps; como consecuencia, en nuestro estudio tuvo una baja frecuencia (2,2%). Por otro lado, el HLA*B1302 ha tenido relación con la enfermedad y su inicio temprano, en población sana colombiana se ha descrito en 0,92%, en nuestro grupo se encuentra de manera significativa en los pacientes sin establecerse asociación clínica. Pocos estudios previos refieren resultados de HLA en APs en Colombia.

[Faecal microbiota study reveals specific dysbiosis in spondyloarthritis according to subtype, disease activity and treatment]. / Estudio de microbiota fecal revela disbiosis específica en espondiloartritis, según subtipo, actividad de la enfermedad y tratamiento.

OBJECTIVE: To compare the diversity and composition of the gastrointestinal microbiome of patients with SpA. METHODS: MiSeq sequencing of the V3-V4 region of the 16S ribosomal RNA gene was performed on DNA isolated from stool. Patients with concurrent SpA and IBD were excluded. Differences were assessed for richness and diversity indices by QIIME 2™. Differences between means >0,2% with a p-value<0,05 were assumed significant. Institutional Ethics Committee endorsement. RESULTS: 69 individuals included, 49 with SpA (ankylosing spondylitis-AS 72,9%, psoriatic arthritis-PsA 18,8%, reactive arthritis-ReA 8,3%) 5 positive controls-dysbiosis and 15 controls-eubiosis. Conventional treatment in 42,9%, anti-IL-17 16,3% and anti-TNF 40,8%. By subtype, statistically significant differences in favour of AS were found for the diversity indices. AS vs PsA there was a difference in favour of AS for Clostridium clostridioforme (p=0,002), Gemmiger formicilis (p=0,009), Roseburia inulivorans (p=0,008) and Lachnospira pectinoschiza. AS vs ReA there was a difference in favour of AS for L. pectinoschiza (p=0,009), Ruminococcus callidus (p=0.006), Clostridium ruminantium (p=0.031); G. formicilis (p=0,034). Diversity and richness showed differences in patients with high activity for Simpson's and Pielou's indices. In high activity, lower enrichment of Bacteroides eggerthii (p= 0,0003), C. ruminantium (p= 0,026) and Alistipes putredinis (p=0,035) was found. The number of ASV was higher in the anti-IL-17 vs conventional group (p=0.025) and a trend between anti-IL-17 vs anti-TNF (p=0.09). In anti-TNF there was a lower proportion for C. clostridioforme (p=0.023), G. formicilis (p=0.030) and R. callidus (p= 0.003). In anti IL-17, Alistipes indistinctus (p= 0.012) was decreased. CONCLUSIONS: There are differences in microbial diversity for SpA subtypes. The level of disease activity is plausible to influence the composition of the faecal microbiota. Anti-TNFα treatment may influence the microbiome environment favouring restoration of the gut microbiota, while anti-IL-17 may maintain an inflammatory environment.

OBJETIVO: Comparar la diversidad y composición del microbioma gastrointestinal de pacientes con EspA. MÉTODOS: La secuenciación MiSeq de la región V3-V4 del gen ARN ribosomal 16, se realizó en ADN aislado de heces. Se excluyeron pacientes con EspA y EII simultánea. Se evaluaron diferencias para los índices de riqueza y diversidad por medio de QIIME 2™. Las diferencias entre medias> 0,2%, con un valor de p< 0,05, se asumieron significativas. Aval del Comité de Ética Institucional. RESULTADOS: 69 individuos incluidos, 49 con EspA (espondilitis anquilosante-EA 72,9%, artritis psoriásica-APs 18,8%, artritis reactiva-ARe 8,3%), cinco controles positivos-disbiosis y 15 controles-eubiosis. El tratamiento convencional en 42,9%, anti-IL-17 16,3%, y anti-TNF 40,8%. Por subtipo-EasP, se encontraron diferencias estadísticamente significativas a favor de EA para los índices de diversidad. Entre EA vs APs, hubo diferencia a favor de EA para Clostridium clostridioforme (p=0,002), Gemmiger formicilis (p=0,009), Roseburia inulivorans (p=0,008) y Lachnospira pectinoschiza. Entre EA vs ARe hubo diferencia a favor de EA para L. pectinoschiza (p=0,009), Ruminococcus callidus (p = 0,006), Clostridium ruminantium (p=0,031); G. formicilis (p=0,034). La diversidad y riqueza mostraron diferencias en pacientes con alta actividad para los índices de Simpson y Pielou. En alta actividad, se encontró menor enriquecimiento de Bacteroides eggerthii (p=0,0003), C. ruminantium (p= 0,026) y Alistipes putredinis (p= 0,035). El número de ASV fue superior en el grupo de anti IL-17 vs convencional (p=0.025), y una tendencia entre anti IL-17 vs anti-TNF (p=0,09). En anti TNF hubo menor proporción para C. clostridioforme (p=0,023), G. formicilis (p=0,030) y R. callidus (p= 0,003). Y en anti IL-17, Alistipes indistinctus (p= 0,012), estuvo disminuida. CONCLUSIONES: Existen diferencias en la diversidad microbiana para los subtipos de EspA. El nivel de actividad de la enfermedad es plausible para influir en la composición de microbiota fecal. El tratamiento con anti-TNFα, puede influenciar el ambiente del microbioma favoreciendo la restauración de la microbiota intestinal, mientras los anti IL-17 podrían mantener un ambiente inflamatorio.

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.

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.

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.

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.

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.