TRAIL and TRAIL receptors splice variants during long-term interferon ß treatment of patients with multiple sclerosis: evaluation as biomarkers for therapeutic response.

OBJECTIVE: We aimed to assess the effects of interferon ß (IFNß) treatment on the expression of the splice variants of the Tumour necrosis factor-Related Apoptosis Inducing Ligand (TRAIL) and its receptors in different cell subpopulations (CD14+, CD4+ and CD8+) from patients with multiple sclerosis (MS), and to determine whether this expression discriminated responders from non-responders to IFNß therapy. METHODS: We examined mRNA expression of the TRAIL and TRAIL receptors variants in patients with MS, at baseline and after one year of IFNß therapy, according to responsiveness to this drug. RESULTS: Long-term therapy with IFNß increased the expression of TRAIL-α in T cell subsets exclusively from responders and decreased the expression of the isoform 2 of TRAILR-2 in monocytes from responders as well as non-responders. Lower expression of TRAIL-α, and higher expression of TRAIL-ß in monocytes and T cells, was found before the onset of IFNß therapy in patients who will subsequently become responders. Baseline expression of TRAILR-1 was also significantly higher in monocytes and CD4+ T cells from responders. CONCLUSIONS: The present study shows that long-term IFNß treatment has a direct influence on TRAIL-α and TRAILR-2 isoform 2 expression. Besides, receiver operating characteristic analysis revealed that the baseline expression of TRAIL-α in monocytes and T cells, and that of TRAILR-1 in monocytes and CD4+ T cells, showed a predictive value of the clinical response to IFNß therapy, pointing to a role of TRAIL system in the mechanism of action of IFNß in MS that will need further investigation.

SARS-CoV-2 Infection in Multiple Sclerosis: Results of the Spanish Neurology Society Registry.

OBJECTIVE: To understand COVID-19 characteristics in people with multiple sclerosis (MS) and identify high-risk individuals due to their immunocompromised state resulting from the use of disease-modifying treatments. METHODS: Retrospective and multicenter registry in patients with MS with suspected or confirmed COVID-19 diagnosis and available disease course (mild = ambulatory; severe = hospitalization; and critical = intensive care unit/death). Cases were analyzed for associations between MS characteristics and COVID-19 course and for identifying risk factors for a fatal outcome. RESULTS: Of the 326 patients analyzed, 120 were cases confirmed by real-time PCR, 34 by a serologic test, and 205 were suspected. Sixty-nine patients (21.3%) developed severe infection, 10 (3%) critical, and 7 (2.1%) died. Ambulatory patients were higher in relapsing MS forms, treated with injectables and oral first-line agents, whereas more severe cases were observed in patients on pulsed immunosuppressors and critical cases among patients with no therapy. Severe and critical infections were more likely to affect older males with comorbidities, with progressive MS forms, a longer disease course, and higher disability. Fifteen of 33 patients treated with rituximab were hospitalized. Four deceased patients have progressive MS, 5 were not receiving MS therapy, and 2 were treated (natalizumab and rituximab). Multivariate analysis showed age (OR 1.09, 95% CI, 1.04-1.17) as the only independent risk factor for a fatal outcome. CONCLUSIONS: This study has not demonstrated the presumed critical role of MS therapy in the course of COVID-19 but evidenced that people with MS with advanced age and disease, in progressive course, and those who are more disabled have a higher probability of severe and even fatal disease.

Killer-cell immunoglobulin-like receptor expression on lymphocyte subsets in multiple sclerosis patients treated with interferon-ß: evaluation as biomarkers for clinical response.

BACKGROUND: Both the adaptative and the innate immune systems interplay in multiple sclerosis (MS) pathogeny. Killer-cell immunoglobulin-like receptors (KIRs) are key regulators of the immune response, with activating and inhibitory isoforms. OBJECTIVE: In this study we analysed whether the expression of KIR isoforms is implicated in MS pathogenesis and in the therapeutic response to interferon (IFN)-ß. METHODS: Peripheral blood samples were collected from 78 IFN-ß-treated MS patients and 46 healthy controls (HC). KIR expression was evaluated by flow cytometry on natural killer (NK) and T cells. RESULTS: The expression of KIRs on NK cells and T lymphocytes did not differ between MS patients and HC. IFN-ß therapy decreased the expression of KIR2DL1/2DS1 and increased that of KIR2DL2/3 on NK cells. This therapy also reduced KIR2DL1/2DS1, KIR2DL2/2DL3 and KIR3DL2 expression on CD8(+) T cells. The baseline evaluation of the percentage of circulating CD16(+) NK cells was predictive of the clinical response to IFN-ß; however, response to this therapy did not appear related to KIR expression. CONCLUSIONS: This study shows that expression of KIR isoforms on NK and T lymphocytes correlated in different ways with IFN-ß therapy, suggesting that KIR dynamics may be associated with the pathways involved in the mechanisms of action of IFN-ß.

Validación transcultural al castellano del Actionable Bladder Symptoms Screening Tool / Transcultural validation in Spanish of the Actionable Bladder Symptoms Screening Tool

Introducción. Los trastornos del tracto urinario inferior son frecuentes en pacientes con esclerosis múltiple a lo largo del transcurso de la enfermedad y alcanzan prevalencias variables cercanas al 75%. Es primordial realizar un diagnóstico precoz en fases tempranas y un abordaje terapéutico óptimo. Burks et al elaboraron el Actionable Bladder Symptoms Screening Tool (ABSST) como herramienta de cribado útil de dichos trastornos. Posteriormente, Bates et al desarrollaron una versión corta del ABSST con el objetivo de minimizar el tiempo de realización y facilitar su manejo. Objetivo. Realizar la validación transcultural al castellano de la versión breve del ABSST. Pacientes y métodos. Se realizó la traducción al castellano del ABSST y una posterior retrotraducción al inglés que confirmaba su equivalencia semántica. Se llevó a cabo una prueba de campo en 40 pacientes con esclerosis múltiple, incluyendo dos preguntas finales para comprobar la comprensión y aceptabilidad de la herramienta y un último ítem que recogía el tiempo empleado para su realización. Resultados: Se seleccionaron 40 pacientes conforme a los criterios de inclusión y exclusión; el 67,5% eran mujeres y la media global de edad era de 46,2 años. La comprensión del test fue del 100%, y la aceptabilidad, del 97,5%. El 57,5% obtuvo puntuaciones >= 3, y se emplearon 5,33 minutos de media. Conclusiones. El ABSST como cuestionario de cribado breve de trastornos urinarios en la esclerosis múltiple es una herramienta útil para su detección temprana y queda validado para su uso en castellano (AU)

Introduction. Disorders of the lower urinary tract are frequent in patients with multiple sclerosis throughout the course of the disease and reach variable prevalences close to 75%. It is essential to obtain an early diagnosis in the initial phases and to implement an optimal therapeutic management. Burks et al developed the Actionable Bladder Symptoms Screening Tool (ABSST) as a useful screening test in such disorders. Later, Bates et al developed a short version of the ABSST with the objective of minimising the time required to complete it and making it easier to use. AIMS. To carry out the transcultural validation into Spanish of the short version of the ABSST. Patients and Methods: The ABSST was translated into Spanish and then back-translated into English, which confirmed the semantic equivalence. A field test was conducted on 40 patients with multiple sclerosis, with two extra questions being included at the end in order to check the comprehension and acceptability of the tool, together with a final item that asked for the time spent on completing it. Results: Forty patients were selected In accordance with the eligibility and exclusion criteria; 67.5% of them were females and the overall mean age was 46.2 years. The rate of comprehension of the test was 100%, and that of acceptability was 97.5%. Results showed that 57.5% obtained scores >= 3, and an average of 5.33 minutes were spent on completing it. Conclusions: As a brief screening questionnaire for urinary disorders in multiple sclerosis, the ABSST is a useful tool for detecting them at an early stage and has now been validated for use in Spanish (AU)