Test de respiración única para la capacidad de difusión de monóxido de carbono (DLCO) y su interpretación en enfermedades autoinmunes

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 oxigeno en contra del gradiente normal de tensión provisto por el aire inspirado

Posttranslational modifications in psoriatic arthritis: A systematic literature review

Antecedentes y objetivos: La artritis psoriásica (APs) es una enfermedad inflamatoria compleja. Las modificaciones postraduccionales influyen en casi todos los aspectos de la biología celular normal y la patogénesis. El objetivo de esta revisión sistemática era recopilar todas las pruebas publicadas sobre las modificaciones postraduccionales en la APs, y el resultado principal era evaluar una asociación entre los resultados de la enfermedad y las modificaciones postraduccionales específicas en la APs. Métodos: Se realizó una búsqueda electrónica sistemática en las bases de datos Medline, PubMed, Cochrane, Virtual Health Library y Embase. Se identificaron 587 artículos; 59 fueron evaluados tras eliminar duplicados y escaneados, de los cuales 47 fueron incluidos. Se realizó un análisis descriptivo, agrupando los resultados según el tipo de modificación postraduccional evaluada. El protocolo se registró en la base de datos PROSPERO. Resultados: Se identificaron siete modificaciones postraduccionales: citrulinación, carbamilación, fosforilación, glucosilación, acetilación, metilación y estrés oxidativo. El péptido anticitrulinado y la proteína anticarbamilada se han evaluado en la artritis reumatoide. Actualmente existe información que sugiere que estos anticuerpos pueden ser útiles para mejorar el diagnóstico de la APs y que pueden demostrar una correlación con una peor progresión de la enfermedad (erosiones, afectación poliarticular y mala respuesta al tratamiento). La glicosilación se asoció con un aumento de la inflamación y los productos de fosforilación relacionados con la expresión de SIRT2 y pSTAT3 o la presencia de Th17 y la citoquina interleucina-22, lo que sugiere una posible diana terapéutica.Conclusiones:Las modificaciones postraduccionales a menudo desempeñan un papel clave en la modulación de la función de las proteínas en la APs y se correlacionan con los resultados de la enfermedad.La citrulinación, la carbamilación, la fosforilación, la glucosilación, la acetilación, la metilación y el estrés oxidativo se identificaron como factores asociados con el diagnóstico y el pronóstico.© 2023 Los autoresBackground 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. © 2023 The Author(s

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

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

El efecto de interacción de los títulos de anticuerpos anti-RgpA y anti-PPAD: Un indicador para el diagnóstico de la artritis reumatoide

Porphyromonas gingivalis secreta factores de virulencia como Arg-gingipains y peptidil arginina deiminasa (PPAD), que están asociados con la patogénesis de la artritis reumatoide (AR). Sin embargo, no existe información sobre los títulos de anticuerpos frente a estas enzimas bacterianas como indicadores sistémicos o biomarcadores en la AR. En este estudio transversal se evaluó a 255 individuos: 143 con diagnóstico de AR y 112 sin AR. Se utilizaron modelos de regresión logística ajustados por edad, sexo, índice metabólico basal, tabaquismo y gravedad de la periodontitis para evaluar la asociación de la AR con el factor reumatoide (FR), los anticuerpos antiproteínas citrulinadas (ACPA), la velocidad de sedimentación globular, la proteína C reactiva de alta sensibilidad, los anti-RgpA, los anti-PPAD y los anti-RgpA/anti-PPAD doblemente positivos. Se observó que el FR (odds ratio [OR] 10,6; intervalo de confianza [IC] del 95%: 4,4-25), los ACPA (OR 13,7; IC del 95%: 5,1-35) y la doble positividad anti-RgpA/anti-PPAD (OR 6,63; IC del 95%: 1,61-27) se asociaban con el diagnóstico de AR. Los anti-RgpA también se asociaron con la AR (OR 4,09; IC 95%: 1,2-13,9). La combinación de anti-RgpA/anti-PPAD mostró una elevada especificidad del 93,7% y un VPP del 82,5% en la identificación de individuos con AR. Los anticuerpos anti-RgpA se asociaron con el índice inflamatorio periodontal en individuos con AR (p < 0,05). La doble positividad de los anticuerpos anti-RgpA/anti-PPAD mejoró el diagnóstico de AR. Por lo tanto, los anticuerpos RgpA y anti-RgpA/anti-PPAD pueden ser biomarcadores de la AR.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 R

Single breath carbon monoxide diffusing capacity (DLCO) test and its interpretation in autoimmune diseases. Application in clinical practice Part - II

13 páginasThe 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.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

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

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

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

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

Association and predictability of antibodies and levels drug anti-TNF α with clinical response in patients with rheumatoid arthritis and spondyloarthritis treated with anti-TNF Biologics in Central Military Hospital.

Objetivo: Evaluar asociación y la capacidad de predicción de los niveles de medicamento anti-TNF α y de anticuerpos contra anti-TNF α con relación a la respuesta clínica en pacientes con Artritis Reumatoide (AR) y Espondiloartritis (EAS) tratados con terapia biológica anti- TNF α en el Hospital Militar Central. Metodología: Estudio observacional analítico de cohorte. Pacientes con AR y EAS tratados con Adalimumab (ADA), Etanercept (ETN) e Infliximab (IFX) entre el 2012 y 2015. Muestreo a conveniencia. Se efectúo análisis bivariado y se calculó la chi-cuadrado como medida de asociación entre la concentración de anti TNF y los anticuerpos contra anti TNF de cada biológico, con las variables de desenlace clínico DAS28 (28 joint Disease activity Score) por VSG y PCR, CDAI (Clinical Disease activity Index), SDAI (Simple Disease activity index) y HAQ-DI (Health Assessment Questionnaire Disability Index) en AR, y BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) y BASFI (Bath Ankylosing Spondylitis Functional Index) en EAS. Mediante regresión lineal múltiple se evaluó si la concentración de medicamento y los anticuerpos predecían la respuesta clínica para AR y EAS. En una cohorte de pacientes con AR y EAS se realizó una comparación de mediciones clínicas por criterios de respuesta EULAR y BASDAI50 respectivamente, para valorar la tasa de respuesta al tratamiento. Resultados: n= 51 para AR, n=48 para EAS. Los niveles totales de medicamentos (p=0,08, p=0,042, p= 0,047) especialmente ADA e IFX en AR así como los de IFX (p= 0,034) en las EAS se asociaron con actividad. Los anticuerpos contra anti-TNF no se asociaron con la respuesta clínica en pacientes AR, pero, en EAS si hubo asociación ente los niveles totales de anticuerpos contra anti-TNF y la actividad de la enfermedad (p=0,027). Los niveles de medicamentos anti-TNF y los anticuerpos contra anti-TNF no predijeron la respuesta clínica en los pacientes con AR ni en las EAS. En la cohorte evaluada la mayoría de los pacientes con AR tuvieron respuesta moderada y los de EAS pobre respuesta. Conclusión: Los niveles de medicamentos anti-TNF y los anticuerpos contra anti-TNF se asocian con la actividad de la enfermedad pero no la predicen.Subdirección de investigaciones del Hospital Militar CentralQuimiolab LTDAProgenicaObjective: To assess association and the predictability of drug anti-TNF α and levels of antibodies against anti-TNF α in relation to clinical response in patients with rheumatoid arthritis (RA) and Spondylarthritis (SpA) treated with biologic therapy anti - TNF α in the Central Military Hospital. Methods: Observational study analytical cohort. Patients with AR and EAS treated with Adalimumab (ADA), Etanercept (ETN) and Infliximab (IFX) between 2012 and 2015. Convenience sampling. Bivariate analysis was carried out and calculated the chi-square as a measure of association between the concentration of anti-TNF and antibodies against anti-TNF of each biological, with the variables of outcome DAS28 (28 joint Disease activity Score) VSG and PCR, CDAI (Clinical Disease activity Index), SDAI (Simple Disease activity index), HAQ-DI (Health Assessment Questionnaire Disability Index) for AR, and BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) , BASFI (Bath Ankylosing Spondylitis Functional Index) BASDAI, BASFi for SpA. Using multiple linear regression assessed if the drug concentration and antibodies predicted the clinical response to AR and SpA. In a cohort of patients with AR and SpA were performed a comparison of clinical measurements by EULAR response criteria and BASDAI50 respectively, to assess the rate of response to treatment. Results: n = 51 for AR, n = 48 for SpA. Total levels of drugs (p=0,08, p=0,042, p= 0,047) especially ADA and IFX for AR, as well as those of IFX (p= 0,034) for SpA were associated with the activity. Anti-TNF antibodies were not associated with clinical response in RA patients, but in SpA there was an association between total levels of antibodies against anti-TNF and the disease activity(p=0,027). Levels of anti-TNF drugs and anti-TNF antibodies did not predict the clinical response in patients with RA or SpA. In the cohort evaluated the majority of patients with RA had moderate response and SpA had poor response. Conclusion: The levels of anti-TNF drugs and anti-TNF antibodies are associated with disease activity, but they do not predict it