[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.

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.

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.

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.

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.

¿Cuáles son los beneficios de la rehabilitación cardiopulmonar en la capacidad física y la calidad de vida de los pacientes con hipertensión pulmonar asociada a enfermedades del tejido conectivo? / What are the benefits of cardiopulmonary rehabilitation on the physical capacity and quality of life of patients with pulmonary hypertension with connective tissue diseases?

La hipertensión arterial pulmonar es una condición que produce discapacidad con alteración en la funcionalidad y la calidad de vida de las personas que la padecen. En la hipertensión pulmonar grupo I se encuentran incluidas las personas con enfermedades del tejido conectivo quienes, por su condición de base, presentan mayor morbimortalidad, razón por la cual se describe el beneficio de terapias no farmacológicas como la rehabilitación cardiopulmonar con ejercicio aeróbico y de resistencia, como manejo coadyuvante a las terapias farmacológicas descritas en la mejoría de la capacidad física y la calidad de vida.

Pulmonary arterial hypertension is a condition that causes disability with alterations in the functionality and quality of life of those who suffer from it. Group I pulmonary hypertension includes people with connective tissue diseases who, due to their underlying condition, present greater morbimortality, which is why we describe the benefit of non-pharmacological therapies such as cardiopulmonary rehabilitation with aerobic and resistance exercise, as an adjuvant management to the pharmacological therapies described in the improvement of physical capacity and quality of life.

Drug Levels and Antibodies Against TNF-blockers in Spondyloarthritis and Rheumatoid Arthritis are Associated with the Activity but they do Not Predict it.

BACKGROUND: Many patients may have resistance to TNF-blockers. These drugs may induce neutralizing antibodies. The determination of the drug levels of TNF-blockers and Anti-Drug Antibodies (ADAs) against TNF-blockers may help to make clinical decisions. OBJECTIVES: The objective of this study was to associate and predict the drug levels of TNFblockers and ADAs in relation to disease activity in patients with Spondyloarthritis (SpA) and Rheumatoid Arthritis (RA). METHODS: Cross-sectional study including patients fulfilling ASAS classification criteria for SpA and 2010 ACR-EULAR classification criteria for RA. These patients were treated with Adalimumab (ADA), Infliximab (IFX), and Etanercept (ETN). A bivariate analysis and the chi-square test were performed to evaluate the association of ADAs and drug levels with activity measures for SpA and RA. Five regression models analyzing drug levels, ADAs and disease activity measures using a multiple linear regression were performed in order to evaluate the prediction of ADAs and drug levels in relation to disease activity. RESULTS: In SpA, IFX levels were associated with BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) (p=0.034). In RA, total drug levels were associated with DAS28-ESR (28 joint Disease activity Score-erythrocyte sedimentation rate), (p=0.008), DAS28-CRP (p=0.042), CDAI (Clinical Disease Activity Index) (p=0.047) and SDAI (Simple Disease activity index), (p=0.017). ADA levels had association with CDAI (p=0.002) and SDAI (p=0.002). IFX levels were associated with a DAS28-ESR (p=0.044), DAS28-CRP (p=0.022) and SDAI (p=0.022). ADAs were associated in SpA with BASDAI (p=0.027). Drug levels and ADAs did not predict disease activity in patients with SpA or RA. CONCLUSION: ADAs and drug levels of anti-TNF are associated with disease activity measures in patients with SpA and RA. However, they cannot predict clinical activity in these conditions.

Dickkopf 1 protein and its association with joint deterioration in rheumatoid arthritis: Systematic review / Dickkopf 1 protein and its association with joint deterioration in rheumatoid arthritis. Systematic review

ABSTRACT Background: Rheumatoid arthritis (RA) is an autoimmune disease that is mainly characterized by joint deterioration and decreased bone mineral density. The Dickkopf 1 protein (DKK1) exerts a negative regulatory function of the Wnt pathway involved in the differentiation of osteoblasts, and has been observed to be overexpressed in patients with RA. Objective: To provide updated information on current knowledge about the relationship between DKK1 serum levels and the presence of bone and joint damage in RA patients. Method: A qualitative systematic review was carried out in the PubMed, Embase, Cochrane and Scielo databases using the terms Dickkopf 1, DKK1, Dickkopf related protein 1, Rheumatoid Arthritis, and Bone biomarker. Results: A total of 12 studies were chosen that met the requirements of the search. These included 7 prospective cohorts, 4 cross-sectional studies, and 1 clinical trial. Of the 12 studies reviewed, 10 analyzed the relationship between serum DKK1 levels and the presence of bone damage as the primary outcome. One of them analyzed this relationship as a secondary outcome and another one the RSP01/DKK1 ratio. The results to date seem to indicate that DKK1 could have an active role in advanced stages of RA, but not in the initial phase. Conclusions: The DKK1 protein plays an essential pathophysiological role in the decrease of bone mass and joint remodelling, depending on the stage of the disease in patients with RA. Its role as a biomarker or therapeutic strategy would be an interesting alternative still under study.

RESUMEN Antecedentes: La artritis reumatoide (AR) es una enfermedad autoinmune caracterizada prin cipalmente por deterioro articular y disminución de la densidad mineral ósea. La proteína Dickkopf 1 (DKK1) ejerce una función reguladora negativa de la vía Wnt comprometida con la diferenciación de osteoblastos y se ha observado que puede estar sobreexpresada en pacientes con AR. Objetivo: Proveer información actualizada sobre el conocimiento de la asociación entre los niveles séricos de DKK1 y la presencia de dafño óseo y articular en pacientes con AR. Método: Se realizó una revisión sistemática cualitativa en las bases de datos Pubmed, Embase, Cochrane y Scielo utilizando los términos Dickkopf 1, DKK1, Dickkopf related pro tein 1, rheumatoid artrhitis, biomarcador, resorción ósea. Resultados: Se escogieron 12 estudios que llenaban los requisitos de la búsqueda; 7 fueron cohortes prospectivas, 4 estudios de corte transversal y uno ensayo clínico. De los 12 estudios revisados, 10 analizaron la asociación entre niveles séricos de DKK1 y presencia de dann o óseo como desenlace primario. Uno de ellos analizó esta asociación como desenlace secundario y otro la relación RSP01/DKK1. Los resultados hasta la fecha parecen indicar que la DKK1 tendría un papel activo en estadios avanzados de AR y no en la fase inicial. Conclusiones: La proteína DKK1 desempeña un papel fisiopatológico esencial en la disminu ción de la masa ósea y la remodelación articular, dependiendo de la fase de la enfermedad, en pacientes con AR. Su papel como biomarcador o estrategia terapéutica sería una interesante alternativa aún en estudio.

Are obesity, ACPAs and periodontitis conditions that influence the risk of developing rheumatoid arthritis in first-degree relatives?

The aim of this study was to investigate the body mass index (BMI), anti-citrullinated protein antibodies (ACPAs) status and the presence of periodontitis and IgG-1/IgG-2 antibodies against Porphyromonas gingivalis (Pg) in the first-degree relatives (FDRs) of rheumatoid arthritis (RA) patients and compare these variables with a control group of healthy individuals from the general population. In total, 100 FDR individuals and 200 healthy controls matched by age and gender were included. Rheumatologic and periodontal assessment was performed, and the presence of ACPAs and anti-P. gingivalis antibodies was evaluated. Groupwise comparisons were analysed using the McNemar and Wilcoxon tests. A conditional logistic regression analysis was performed to establish the associations between BMI, ACPAs and periodontitis in both groups. In the FDR group, 70% of the subjects were female, with a mean age of 37.3 ± 13 years. Obesity was observed in 17 and 7% of the FDRs and controls, respectively. ACPAs were found in 7% of the FDRs vs. 2.5% of the controls. Periodontitis was diagnosed in 79 and 56% of the FDRs and controls, respectively. Among the FDRs, 15% had severe periodontitis. There were associations in the FDR group related to the presence of obesity (OR 2.93, 95% CI 1.03-8.28), ACPAs (OR 2.45, 95% CI 0.7-8.32) and periodontitis (OR 3.70 95% CI 1.89-7.29). Regarding anti-P. gingivalis antibodies and smoking history, no differences were found between the groups. Obesity, ACPAs and periodontitis (diagnosis and severity) can be considered as relevant conditions associated with the development of RA in FDRs.

Pulmonary alveolar microlithiasis / Microlitiasis alveolar pulmonar

Pulmonary alveolar microlithiasis is an uncommon disease of unknown etiology, and is characterized by the presence of multiple sub-pleural and intra-alveolar microcalcifications. We present the case of a patient with rheumatoid arthritis and chronic renal disease, but with no respiratory symptoms.

La microlitiasis pulmonar alveolar es una enfermedad infrecuente, de etiología desconocida, caracterizada por la presencia de múltiples microcalcificaciones intraalveolares y subpleurales. Presentamos el caso de un paciente asintomático respiratorio, con historia clínica de artritis reumatoide y enfermedad renal crónica.

Test de respiración única para la capacidad de difusión de monóxido de carbono (DLCO) y su interpretación en enfermedades autoinmunes. Aplicación en la práctica clínica -Segunda Parte- / Single breath carbon monoxide diffusing capacity (DLCO) test and its interpretation in autoimmune diseases. Application in clinical practice Part -II-

El test de respiración única ha probado por si mismo ser una parte esencial del tamizaje de rutina de la función pulmonar, y de igual valor que la espirometría. A pesar de 100 años de investigación, aún no existe certeza sobre la relativa importancia de las membranas alveolo-capilares vs los eritrocitos como los pasos que sean delimitantes en el transporte global del monóxido de carbono del gas hacia la sangre, pero esto es solo un problema cuantitativo. La naturaleza esencial del test de DLCO ya ha sido elucidada, siendo F.J.W. Roughton y R.E. Forster los mayores protagonistas en esta descripción. La interpretación de la DLCO, en conjunto con la espirometría y los volúmenes pulmonares, pueden contribuir en la evaluación de enfermedades pulmonares subyacentes y, en el campo reumatológico es esencial su conocimiento puesto que ofrece la posibilidad de establecer un diagnóstico diferencial y un seguimiento cercano de los pacientes con enfermedades autoinmunes con manifestaciones pulmonares. El test de espiración única para la capacidad de difusión de monóxido de carbono, la espirometría y los gases arteriales son los test de función pulmonar más ampliamente utilizados para la evaluación y tratamiento de pacientes.

The single breath DLCO (TLCO) has proved as an essential part of the routine pulmonary function screen, similar to spirometry. In spite of nearly 100 years research, there is still concern over the relative importance of the alveolarcapillary membranes versus the red cells as rate limiting steps in the overall transfer of carbon monoxide from gas to blood, but this is only a quantitative problem. The essential nature of the DLCO has already been elucidated by F.J.W. Roughton and R.E. Forster having played the major roles. Interpreting the DLCO, in conjunction with spirometry and lung volumes assessment, may assist in diagnosing the underlying disease and in the Rheumatology field it is essential it's knowledge because it offers the possibility of establish the differential diagnosis and a close follow-up of the patients with pulmonary manifestations in autoimmune diseases.

Test de respiración única para la capacidad de difusión de monóxido de carbono (DLCO) y su interpretación en enfermedades autoinmunes. Historia y bases fisiológicas / Single breath carbon monoxide diffusing capacity (DLCO) test and its interpretation in autoimmune diseases. History and physiological basis

El test de respiración única para la capacidad de difusión de monóxido de carbono (DLCO) tiene una larga historia desde su nacimiento por Krogh y Krogh en 1909 hasta la primera publicación, describiendo una técnica estandarizada para la medición de la capacidad de difusión (DLCO) por Ogilvie en 1957. El test de DLCO fue inicialmente ideado como una herramienta fisiológica para evaluar el concepto (ahora abandonado) de que el pulmón, al igual que la vejiga natatoria de algún pez marino de agua profunda, podía secretar oxígeno en contra del gradiente normal de tensión provisto por el aire inspirado. El test de DLCO fue introducido como una prueba clínica por Marie Krogh en 1915, pero la medida nunca engranó debido a que los métodos de medición del monóxido de carbono eran muy engorrosos. En los años cincuenta con la introducción del medidor infrarrojo de monóxido de carbono (CO) (desarrollado en Alemania en la Segunda Guerra Mundial), el interés en el test de DLCO revivió y varios métodos para realizar el test de DLCO en pacientes con enfermedades pulmonares se aplicaron, usándose étodos en estado estable, la respiración única y las técnicas de reinhalación.

The single breath test of carbon monoxide (CO) uptake has a long history /from its birth by Krogh and Krogh in 1909 to the first publication describing a standardized technique for the diffusing capacity measurement (DLCO) by Ogilvie in 1957. The DLCO was devised originally as a physiological tool to test the notion (now abandoned) that the lung, like the swim bladder of some deep-sea fish, could secrete oxygen against the normal tension gradient provided by inspired air. The DLCO was introduced as a clinical test by Marie Krogh in 1915, but the measurement never caught on because methods of measuring carbon monoxide were so cumbersome. In the 1950s, with the introduction of the infra-red CO meter (developed in Germany, in World War II) interest in the DLCO revived, and several different methods for measuring DLCO in patients with pulmonary diseases were in use various steady state methods, the single breath and rebreathing techniques.