Colitis ulcerosa con afectación periapendicular. Estudio de casos y controles

La colitis ulcerosa (CU) es caracteritza per una afectació contínua de la mucosa rectal en sentit proximal cap a altres zones del còlon. Hi ha formes de CU amb afectació distal i periapendicular (CU-PA). Objectius: avaluar la prevalença de la CU-PA, i comparar les seves característiques clíniques, terapèutiques i evolutives. Mètodes: 14 pacients amb CU-PA van ser comparats en termes d'evolució clínica amb 25 pacients amb CU distal sense afectació periapendicular. Resultats: Es va trobar una major freqüència de CU-PA en homes (p = 0,047), sense diferències en la resta de les variables comparades entre els dos grups de pacients.La colitis ulcerosa (CU) se caracteriza por una afectación continua de la mucosa rectal en sentido proximal hacia otras zonas del colon. Existen formas de CU con afectación parcheada distal y periapendicular (CU-PA). Objetivos: evaluar la prevalencia de la CU-PA, y comparar sus características clínicas, terapéuticas y evolutivas. Métodos: 14 pacientes con CU-PA fueron comparados en términos de evolución clínica con 25 pacientes con CU distal sin afectación periapendicular. Resultados: Se halló una mayor frecuencia de CU-PA en hombres (p=0,047), sin diferencias en el resto de las variables comparadas en ambos grupos de pacientes

Immune-mediated inflammatory diseases differently affect IGRAs' accuracy for latent tuberculosis infection diagnosis in clinical practice

Altres ajuts: Sociedad Española de Neumología y Cirugía Torácica (SEPAR); Societat Catalana de Reumatologia (SCR); CERCA Programme/Generalitat de CatalunyaBackground. Clinical accuracy of IGRAs remains unclear on patients with immune-mediated inflammatory diseases (IMIDs). Here, we assess the impact of immunosuppressants and IMIDs on QuantiFERON-TB Gold In-Tube (QFN-G-IT) and T-SPOT.TB accuracy. Methods. Patients with IMIDs who required latent tuberculosis infection (LTBI) screening were enrolled and classified into: (i) 50 patients with inflammatory rheumatic diseases, (ii) 50 patients with psoriasis and (iii) 30 patients with Crohn's disease. A total of 44 healthy individuals without immunosuppression were also included as controls. Tuberculin skin test (TST), T-SPOT.TB and QFN-G-IT assays were performed. IGRAs were performed following manufacturer's instructions. Results. Immunosuppressant's intake was more frequent on patients with Crohn's disease and psoriasis. Positive IGRAs and TST results were reduced in Crohn's disease patients, whereas rate of indeterminate T-SPOT.TB results was increased in this group with respect to the other IMIDs analysed and controls. When IFN-γ response was studied, the levels of this cytokine after mitogen stimulation were significantly lower in Crohn's and inflammatoryrheumatic diseases than in psoriasis. Interestingly, psoriatic patients were the only ones not receiving corticosteroids. Furthermore, a negative correlation was observed between the IFN-γ secreted after mitogen stimulation and corticosteroids dose. Conclusions. IMIDs seem to negatively affect the clinical accuracy of IGRAs, being Crohn's disease patients the most affected individuals due to their concomitant drug-profile and impaired immune response

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Colitis ulcerosa con afectación periapendicular. Estudio de casos y controles

La colitis ulcerosa (CU) es caracteritza per una afectació contínua de la mucosa rectal en sentit proximal cap a altres zones del còlon. Hi ha formes de CU amb afectació distal i periapendicular (CU-PA). Objectius: avaluar la prevalença de la CU-PA, i comparar les seves característiques clíniques, terapèutiques i evolutives. Mètodes: 14 pacients amb CU-PA van ser comparats en termes d'evolució clínica amb 25 pacients amb CU distal sense afectació periapendicular. Resultats: Es va trobar una major freqüència de CU-PA en homes (p = 0,047), sense diferències en la resta de les variables comparades entre els dos grups de pacients.La colitis ulcerosa (CU) se caracteriza por una afectación continua de la mucosa rectal en sentido proximal hacia otras zonas del colon. Existen formas de CU con afectación parcheada distal y periapendicular (CU-PA). Objetivos: evaluar la prevalencia de la CU-PA, y comparar sus características clínicas, terapéuticas y evolutivas. Métodos: 14 pacientes con CU-PA fueron comparados en términos de evolución clínica con 25 pacientes con CU distal sin afectación periapendicular. Resultados: Se halló una mayor frecuencia de CU-PA en hombres (p=0,047), sin diferencias en el resto de las variables comparadas en ambos grupos de pacientes

Estudio de la regulación post-transcripcional de genes mediada por microRNA en pacientes con colitis ulcerosa tratados con glucocorticoides

Antecedentes: La colitis ulcerosa (CU) es una enfermedad inflamatoria intestinal crónica, de etiología desconocida. Los glucocorticoides (GC) constituyen el tratamiento de elección de brotes moderados y graves de CU, pero a pesar de ello hasta un 40% presenta una respuesta inadecuada a los mismos. No se conocen con exactitud los mecanismos asociados a esta mala respuesta, y tampoco somos capaces de predecirla. El uso de moléculas como los microRNAs (miR) en la predicción de respuesta a diferentes tratamientos, es una realidad en otros campos de la medicina, pero su aplicación en la CU es aún limitada. Esta tesis pretende profundizar en el conocimiento de la refractariedad a GC sistémicos a través del estudio del transcriptoma completo (RNAm y miR) de tejido cólico de pacientes con CU. Objetivos: El objetivo principal fue confirmar la existencia de distintos perfiles en el transcriptoma de tejido cólico asociados a una respuesta inadecuada a GC sistémicos en pacientes con brotes moderados y graves de CU. Los objetivos secundarios fueron caracterizar el efecto inmediato de los GC sistémicos sobre el transcriptoma y los mecanismo de acción relacionados con la adecuada e inadecuada respuesta. Material y Métodos: Se recogieron muestras de tejido cólico de pacientes con brotes moderados y graves de CU, antes de iniciar GC sistémicos, y a los 3º días de iniciado los mismos. Los pacientes fueron clasificados en respondedores o Re (actividad leve o inactividad tras 7 días de tratamiento con GC), y no respondedores o noRe (actividad moderada o grave tras 7 días de tratamiento con GC), Además se recogieron muestras de tejido cólico de controles sanos. Las muestras obtenidas fueron estudiadas mediante secuenciación de miR (kit TruSeq Small RNA Sample de Illumina), y microarrays de genoma completo (kit Human HT-12 Expresión v4.0 BeadChip de Illumina), y los resultados de cada grupo se compararon entre si. Posteriormente se utilizaron diferentes herramientas informáticas con la intención de integrar los resultados del estudio experimental y generar un modelo teórico de respuesta al fármaco. Resultados: Se incluyeron 10 controles, y 24 pacientes con brotes moderados o graves de CU tratados con GC. De ellos 13 fueron clasificados como Re, y 11 como noRe a GC. La integridad de las muestras permitió realizar el estudio experimental en 10 pacientes de cada grupo y en 6 controles. Los resultados de la secuenciación mostraron un perfil diferencial de 2 miR antes de iniciar los GC (miR-625-3p; miR-196b-3p) entre el grupo Re y noRe. La comparación realizada entre pacientes Re antes de GC respecto a Re tras 3º días de GC mostró 6 miR diferenciales (miR-183-5p; miR-584-5p; miR-126-5p; miR-625-3p; miR-1271-5p; miR-409-5p), y un RNAm diferencial (DDIT4/REDD1). Y la comparación entre noRe antes de GC y noRe tras 3º días de GC mostró 13 miR diferenciales (miR-200c-3p; miR-18a-5p; miR-192-5p; miR-183-5p; miR-200a-5p; miR-10a-5p; miR-545-5p; miR-132-5p; miR-194-5p; miR-625-3p; miR-1271-5p; miR-409-5p; miR-504-5p). Además el estudio in silico realizado sugiere una posible asociación de la vía mTOR en la respuesta a GC. Conclusiones: En este estudio se demuestra que existe un perfil diferencial en el transcriptoma de tejido cólico de pacientes con brotes moderados o graves de CU Re y noRe a GC sistémicos antes de iniciar el tratamiento. Por otro lado, que dicho transcriptoma se modifica de forma diferente en pacientes Re y noRe en respuesta al tratamiento con GC sistémicos. Podría existir una asociación entre la regulación de la vía mTOR por miR y la respuesta a GC en la CU.Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology. Glucocorticoids (GC) remain the first-line treatment for moderate and severe active disease. However, 40% of patients do not have an appropriate response. We do not know yet the exact underlying mechanism associated with bad response and we are not able to predict it. The utility of molecules like microRNA (miRNA) in the prediction of response to treatments is a reality in other fields of medicine, for example in oncology, but little is known about the utility of these molecules in Inflammatory Bowel Disease. This thesis pretends to delve into refractoriness to GC by studying transcriptome of colonic tissue of patients with ulcerative colitis flares. Objectives: The main objective was to confirm the presence of different colonic transcriptome profiles associated to inadequate response to systemic GC in patients with moderate and severe flares of UC. Secondary objectives were to characterize the immediate effect of systemic GC treatment on the colonic transcriptome, and to determine the mechanism of action related to adequate and inadequate response. Material and Methods: Colic tissue samples of patients with moderate and severe flares of CU were collected before starting GC, and on the 3rd day of treatment. Patients were grouped in responder (less than moderate activity without need for rescue at day 7 of GC) and non-responder (moderate or severe activity at day 7 of GC). In adition, colic tissue samples from healthy controls were collected. Samples were studied by sequencing methods for miR profiles (TruSeq Small RNA Sample kit Illumina), and with microarrays (Human HT-12 kit v4.0 Expression BeadChip Illumina) for hold transcriptome study. Results of each group were compared. Subsequently bioinformatics was used to integrate results and to generate a theoretical model of response to the drug. Results: 10 controls and 24 patients with moderate or severe of UC flares treated with GC were included (13 responders and 11 non-responders to GC). The integrity of samples allowed experimental study in 10 patients of each group and 6 healthy controls. The sequencing results showed a differential miR profile (miR-625-3p, miR-196b-3p) at baseline between responders and non-responders. The comparison between responders before and after treatment show 6 differential miR (miR-183-5p, miR-584-5p, miR-126-5p, miR-625-3p, miR-1271-5p; miR -409-5p), and one differential RNAm (DDIT4 / REDD1). The comparison between non responders before and after GC treatment show 13 differential miR between groups (miR-200c-3p, miR-18a-5p; miR-192-5p, miR-183-5p, miR-200a-5p; miR 10a-5p; miR-545-5p, miR-132-5p, miR-194-5p, miR-625-3p, miR-1271-5p, miR-409-5p, miR-504-5p). In silico study suggests a possible association of the mTOR signaling pathway with the response to glucocorticoids in patients with UC flares and this pathway was used to generate 2 different models of response to GC. Conclusions: This study shows that there is a different profile in the colonic tissue transcriptome of patients with moderate or severe flares of UC responders and non-responders to systemic GC before starting treatment. This colonic transcriptome change with treatment and those changes were different in responders and non-responders. There may be an association between the regulation of the mTOR pathway by miR and the response to GC in UC

Estudio de la regulación post-transcripcional de genes mediada por microRNA en pacientes con colitis ulcerosa tratados con glucocorticoides

Antecedentes: La colitis ulcerosa (CU) es una enfermedad inflamatoria intestinal crónica, de etiología desconocida. Los glucocorticoides (GC) constituyen el tratamiento de elección de brotes moderados y graves de CU, pero a pesar de ello hasta un 40% presenta una respuesta inadecuada a los mismos. No se conocen con exactitud los mecanismos asociados a esta mala respuesta, y tampoco somos capaces de predecirla. El uso de moléculas como los microRNAs (miR) en la predicción de respuesta a diferentes tratamientos, es una realidad en otros campos de la medicina, pero su aplicación en la CU es aún limitada. Esta tesis pretende profundizar en el conocimiento de la refractariedad a GC sistémicos a través del estudio del transcriptoma completo (RNAm y miR) de tejido cólico de pacientes con CU. Objetivos: El objetivo principal fue confirmar la existencia de distintos perfiles en el transcriptoma de tejido cólico asociados a una respuesta inadecuada a GC sistémicos en pacientes con brotes moderados y graves de CU. Los objetivos secundarios fueron caracterizar el efecto inmediato de los GC sistémicos sobre el transcriptoma y los mecanismo de acción relacionados con la adecuada e inadecuada respuesta. Material y Métodos: Se recogieron muestras de tejido cólico de pacientes con brotes moderados y graves de CU, antes de iniciar GC sistémicos, y a los 3º días de iniciado los mismos. Los pacientes fueron clasificados en respondedores o Re (actividad leve o inactividad tras 7 días de tratamiento con GC), y no respondedores o noRe (actividad moderada o grave tras 7 días de tratamiento con GC), Además se recogieron muestras de tejido cólico de controles sanos. Las muestras obtenidas fueron estudiadas mediante secuenciación de miR (kit TruSeq Small RNA Sample de Illumina), y microarrays de genoma completo (kit Human HT-12 Expresión v4.0 BeadChip de Illumina), y los resultados de cada grupo se compararon entre si. Posteriormente se utilizaron diferentes herramientas informáticas con la intención de integrar los resultados del estudio experimental y generar un modelo teórico de respuesta al fármaco. Resultados: Se incluyeron 10 controles, y 24 pacientes con brotes moderados o graves de CU tratados con GC. De ellos 13 fueron clasificados como Re, y 11 como noRe a GC. La integridad de las muestras permitió realizar el estudio experimental en 10 pacientes de cada grupo y en 6 controles. Los resultados de la secuenciación mostraron un perfil diferencial de 2 miR antes de iniciar los GC (miR-625-3p; miR-196b-3p) entre el grupo Re y noRe. La comparación realizada entre pacientes Re antes de GC respecto a Re tras 3º días de GC mostró 6 miR diferenciales (miR-183-5p; miR-584-5p; miR-126-5p; miR-625-3p; miR-1271-5p; miR-409-5p), y un RNAm diferencial (DDIT4/REDD1). Y la comparación entre noRe antes de GC y noRe tras 3º días de GC mostró 13 miR diferenciales (miR-200c-3p; miR-18a-5p; miR-192-5p; miR-183-5p; miR-200a-5p; miR-10a-5p; miR-545-5p; miR-132-5p; miR-194-5p; miR-625-3p; miR-1271-5p; miR-409-5p; miR-504-5p). Además el estudio in silico realizado sugiere una posible asociación de la vía mTOR en la respuesta a GC. Conclusiones: En este estudio se demuestra que existe un perfil diferencial en el transcriptoma de tejido cólico de pacientes con brotes moderados o graves de CU Re y noRe a GC sistémicos antes de iniciar el tratamiento. Por otro lado, que dicho transcriptoma se modifica de forma diferente en pacientes Re y noRe en respuesta al tratamiento con GC sistémicos. Podría existir una asociación entre la regulación de la vía mTOR por miR y la respuesta a GC en la CU.Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology. Glucocorticoids (GC) remain the first-line treatment for moderate and severe active disease. However, 40% of patients do not have an appropriate response. We do not know yet the exact underlying mechanism associated with bad response and we are not able to predict it. The utility of molecules like microRNA (miRNA) in the prediction of response to treatments is a reality in other fields of medicine, for example in oncology, but little is known about the utility of these molecules in Inflammatory Bowel Disease. This thesis pretends to delve into refractoriness to GC by studying transcriptome of colonic tissue of patients with ulcerative colitis flares. Objectives: The main objective was to confirm the presence of different colonic transcriptome profiles associated to inadequate response to systemic GC in patients with moderate and severe flares of UC. Secondary objectives were to characterize the immediate effect of systemic GC treatment on the colonic transcriptome, and to determine the mechanism of action related to adequate and inadequate response. Material and Methods: Colic tissue samples of patients with moderate and severe flares of CU were collected before starting GC, and on the 3rd day of treatment. Patients were grouped in responder (less than moderate activity without need for rescue at day 7 of GC) and non-responder (moderate or severe activity at day 7 of GC). In adition, colic tissue samples from healthy controls were collected. Samples were studied by sequencing methods for miR profiles (TruSeq Small RNA Sample kit Illumina), and with microarrays (Human HT-12 kit v4.0 Expression BeadChip Illumina) for hold transcriptome study. Results of each group were compared. Subsequently bioinformatics was used to integrate results and to generate a theoretical model of response to the drug. Results: 10 controls and 24 patients with moderate or severe of UC flares treated with GC were included (13 responders and 11 non-responders to GC). The integrity of samples allowed experimental study in 10 patients of each group and 6 healthy controls. The sequencing results showed a differential miR profile (miR-625-3p, miR-196b-3p) at baseline between responders and non-responders. The comparison between responders before and after treatment show 6 differential miR (miR-183-5p, miR-584-5p, miR-126-5p, miR-625-3p, miR-1271-5p; miR -409-5p), and one differential RNAm (DDIT4 / REDD1). The comparison between non responders before and after GC treatment show 13 differential miR between groups (miR-200c-3p, miR-18a-5p; miR-192-5p, miR-183-5p, miR-200a-5p; miR 10a-5p; miR-545-5p, miR-132-5p, miR-194-5p, miR-625-3p, miR-1271-5p, miR-409-5p, miR-504-5p). In silico study suggests a possible association of the mTOR signaling pathway with the response to glucocorticoids in patients with UC flares and this pathway was used to generate 2 different models of response to GC. Conclusions: This study shows that there is a different profile in the colonic tissue transcriptome of patients with moderate or severe flares of UC responders and non-responders to systemic GC before starting treatment. This colonic transcriptome change with treatment and those changes were different in responders and non-responders. There may be an association between the regulation of the mTOR pathway by miR and the response to GC in UC

Estudio de la regulación post-transcripcional de genes mediada por microRNA en pacientes con colitis ulcerosa tratados con glucocorticoides /

Antecedentes: La colitis ulcerosa (CU) es una enfermedad inflamatoria intestinal crónica, de etiología desconocida. Los glucocorticoides (GC) constituyen el tratamiento de elección de brotes moderados y graves de CU, pero a pesar de ello hasta un 40% presenta una respuesta inadecuada a los mismos. No se conocen con exactitud los mecanismos asociados a esta mala respuesta, y tampoco somos capaces de predecirla. El uso de moléculas como los microRNAs (miR) en la predicción de respuesta a diferentes tratamientos, es una realidad en otros campos de la medicina, pero su aplicación en la CU es aún limitada. Esta tesis pretende profundizar en el conocimiento de la refractariedad a GC sistémicos a través del estudio del transcriptoma completo (RNAm y miR) de tejido cólico de pacientes con CU. Objetivos: El objetivo principal fue confirmar la existencia de distintos perfiles en el transcriptoma de tejido cólico asociados a una respuesta inadecuada a GC sistémicos en pacientes con brotes moderados y graves de CU. Los objetivos secundarios fueron caracterizar el efecto inmediato de los GC sistémicos sobre el transcriptoma y los mecanismo de acción relacionados con la adecuada e inadecuada respuesta. Material y Métodos: Se recogieron muestras de tejido cólico de pacientes con brotes moderados y graves de CU, antes de iniciar GC sistémicos, y a los 3º días de iniciado los mismos. Los pacientes fueron clasificados en respondedores o Re (actividad leve o inactividad tras 7 días de tratamiento con GC), y no respondedores o noRe (actividad moderada o grave tras 7 días de tratamiento con GC), Además se recogieron muestras de tejido cólico de controles sanos. Las muestras obtenidas fueron estudiadas mediante secuenciación de miR (kit TruSeq Small RNA Sample de Illumina), y microarrays de genoma completo (kit Human HT-12 Expresión v4.0 BeadChip de Illumina), y los resultados de cada grupo se compararon entre si. Posteriormente se utilizaron diferentes herramientas informáticas con la intención de integrar los resultados del estudio experimental y generar un modelo teórico de respuesta al fármaco. Resultados: Se incluyeron 10 controles, y 24 pacientes con brotes moderados o graves de CU tratados con GC. De ellos 13 fueron clasificados como Re, y 11 como noRe a GC. La integridad de las muestras permitió realizar el estudio experimental en 10 pacientes de cada grupo y en 6 controles. Los resultados de la secuenciación mostraron un perfil diferencial de 2 miR antes de iniciar los GC (miR-625-3p; miR-196b-3p) entre el grupo Re y noRe. La comparación realizada entre pacientes Re antes de GC respecto a Re tras 3º días de GC mostró 6 miR diferenciales (miR-183-5p; miR-584-5p; miR-126-5p; miR-625-3p; miR-1271-5p; miR-409-5p), y un RNAm diferencial (01IT4/RE011). Y la comparación entre noRe antes de GC y noRe tras 3º días de GC mostró 13 miR diferenciales (miR-200c-3p; miR-18a-5p; miR-192-5p; miR-183-5p; miR-200a-5p; miR-10a-5p; miR-545-5p; miR-132-5p; miR-194-5p; miR-625-3p; miR-1271-5p; miR-409-5p; miR-504-5p). Además el estudio in silico realizado sugiere una posible asociación de la vía mTOR en la respuesta a GC. Conclusiones: En este estudio se demuestra que existe un perfil diferencial en el transcriptoma de tejido cólico de pacientes con brotes moderados o graves de CU Re y noRe a GC sistémicos antes de iniciar el tratamiento. Por otro lado, que dicho transcriptoma se modifica de forma diferente en pacientes Re y noRe en respuesta al tratamiento con GC sistémicos. Podría existir una asociación entre la regulación de la vía mTOR por miR y la respuesta a GC en la CU.Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology. Glucocorticoids (GC) remain the first-line treatment for moderate and severe active disease. However, 40% of patients do not have an appropriate response. We do not know yet the exact underlying mechanism associated with bad response and we are not able to predict it. The utility of molecules like microRNA (miRNA) in the prediction of response to treatments is a reality in other fields of medicine, for example in oncology, but little is known about the utility of these molecules in Inflammatory Bowel Disease. This thesis pretends to delve into refractoriness to GC by studying transcriptome of colonic tissue of patients with ulcerative colitis flares. Objectives: The main objective was to confirm the presence of different colonic transcriptome profiles associated to inadequate response to systemic GC in patients with moderate and severe flares of UC. Secondary objectives were to characterize the immediate effect of systemic GC treatment on the colonic transcriptome, and to determine the mechanism of action related to adequate and inadequate response. Material and Methods: Colic tissue samples of patients with moderate and severe flares of CU were collected before starting GC, and on the 3rd day of treatment. Patients were grouped in responder (less than moderate activity without need for rescue at day 7 of GC) and non-responder (moderate or severe activity at day 7 of GC). In adition, colic tissue samples from healthy controls were collected. Samples were studied by sequencing methods for miR profiles (TruSeq Small RNA Sample kit Illumina), and with microarrays (Human HT-12 kit v4.0 Expression BeadChip Illumina) for hold transcriptome study. Results of each group were compared. Subsequently bioinformatics was used to integrate results and to generate a theoretical model of response to the drug. Results: 10 controls and 24 patients with moderate or severe of UC flares treated with GC were included (13 responders and 11 non-responders to GC). The integrity of samples allowed experimental study in 10 patients of each group and 6 healthy controls. The sequencing results showed a differential miR profile (miR-625-3p, miR-196b-3p) at baseline between responders and non-responders. The comparison between responders before and after treatment show 6 differential miR (miR-183-5p, miR-584-5p, miR-126-5p, miR-625-3p, miR-1271-5p; miR -409-5p), and one differential RNAm (DDIT4 / REDD1). The comparison between non responders before and after GC treatment show 13 differential miR between groups (miR-200c-3p, miR-18a-5p; miR-192-5p, miR-183-5p, miR-200a-5p; miR 10a-5p; miR-545-5p, miR-132-5p, miR-194-5p, miR-625-3p, miR-1271-5p, miR-409-5p, miR-504-5p). In silico study suggests a possible association of the mTOR signaling pathway with the response to glucocorticoids in patients with UC flares and this pathway was used to generate 2 different models of response to GC. Conclusions: This study shows that there is a different profile in the colonic tissue transcriptome of patients with moderate or severe flares of UC responders and non-responders to systemic GC before starting treatment. This colonic transcriptome change with treatment and those changes were different in responders and non-responders. There may be an association between the regulation of the mTOR pathway by miR and the response to GC in UC

Immune-mediated inflammatory diseases differently affect IGRAs' accuracy for latent tuberculosis infection diagnosis in clinical practice

Altres ajuts: Sociedad Española de Neumología y Cirugía Torácica (SEPAR); Societat Catalana de Reumatologia (SCR); CERCA Programme/Generalitat de CatalunyaBackground. Clinical accuracy of IGRAs remains unclear on patients with immune-mediated inflammatory diseases (IMIDs). Here, we assess the impact of immunosuppressants and IMIDs on QuantiFERON-TB Gold In-Tube (QFN-G-IT) and T-SPOT.TB accuracy. Methods. Patients with IMIDs who required latent tuberculosis infection (LTBI) screening were enrolled and classified into: (i) 50 patients with inflammatory rheumatic diseases, (ii) 50 patients with psoriasis and (iii) 30 patients with Crohn's disease. A total of 44 healthy individuals without immunosuppression were also included as controls. Tuberculin skin test (TST), T-SPOT.TB and QFN-G-IT assays were performed. IGRAs were performed following manufacturer's instructions. Results. Immunosuppressant's intake was more frequent on patients with Crohn's disease and psoriasis. Positive IGRAs and TST results were reduced in Crohn's disease patients, whereas rate of indeterminate T-SPOT.TB results was increased in this group with respect to the other IMIDs analysed and controls. When IFN-γ response was studied, the levels of this cytokine after mitogen stimulation were significantly lower in Crohn's and inflammatoryrheumatic diseases than in psoriasis. Interestingly, psoriatic patients were the only ones not receiving corticosteroids. Furthermore, a negative correlation was observed between the IFN-γ secreted after mitogen stimulation and corticosteroids dose. Conclusions. IMIDs seem to negatively affect the clinical accuracy of IGRAs, being Crohn's disease patients the most affected individuals due to their concomitant drug-profile and impaired immune response

Galectin-8 as an immunosuppressor in experimental autoimmune encephalomyelitis and a target of human early prognostic antibodies in multiple sclerosis.

Galectin-8 (Gal-8) is a member of a glycan-binding protein family that regulates the immune system, among other functions, and is a target of antibodies in autoimmune disorders. However, its role in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system (CNS), remains unknown. We study the consequences of Gal-8 silencing on lymphocyte subpopulations and the development of experimental autoimmune encephalitis (EAE), to then assess the presence and clinical meaning of anti-Gal-8 antibodies in MS patients. Lgals8/Lac-Z knock-in mice lacking Gal-8 expression have higher polarization toward Th17 cells accompanied with decreased CCR6+ and higher CXCR3+ regulatory T cells (Tregs) frequency. These conditions result in exacerbated MOG35-55 peptide-induced EAE. Gal-8 eliminates activated Th17 but not Th1 cells by apoptosis and ameliorates EAE in C57BL/6 wild-type mice. β-gal histochemistry reflecting the activity of the Gal-8 promoter revealed Gal-8 expression in a wide range of CNS regions, including high expression in the choroid-plexus. Accordingly, we detected Gal-8 in human cerebrospinal fluid, suggesting a role in the CNS immune-surveillance circuit. In addition, we show that MS patients generate function-blocking anti-Gal-8 antibodies with pathogenic potential. Such antibodies block cell adhesion and Gal-8-induced Th17 apoptosis. Furthermore, circulating anti-Gal-8 antibodies associate with relapsing-remitting MS (RRMS), and not with progressive MS phenotypes, predicting clinical disability at diagnosis within the first year of follow-up. Our results reveal that Gal-8 has an immunosuppressive protective role against autoimmune CNS inflammation, modulating the balance of Th17 and Th1 polarization and their respective Tregs. Such a role can be counteracted during RRMS by anti-Gal-8 antibodies, worsening disease prognosis. Even though anti-Gal-8 antibodies are not specific for MS, our results suggest that they could be a potential early severity biomarker in RRMS