Role of B Cell Profile for Predicting Secondary Autoimmunity in Patients Treated With Alemtuzumab

UDHEBRONTo explore if baseline blood lymphocyte profile could identify relapsing remitting multiple sclerosis (RRMS) patients at higher risk of developing secondary autoimmune adverse events (AIAEs) after alemtuzumab treatment. Multicenter prospective study including 57 RRMS patients treated with alemtuzumab followed for 3.25 [3.5-4.21] years, (median [interquartile range]). Blood samples were collected at baseline, and leukocyte subsets determined by flow cytometry. We had additional samples one year after the first cycle of alemtuzumab treatment in 39 cases. Twenty-two patients (38.6%) developed AIAEs during follow-up. They had higher B-cell percentages at baseline (p=0.0014), being differences mainly due to plasmablasts/plasma cells (PB/PC, p=0.0011). Those with no AIAEs had higher percentages of CD4+ T cells (p=0.013), mainly due to terminally differentiated (TD) (p=0.034) and effector memory (EM) (p=0.031) phenotypes. AIAEs- patients also showed higher values of TNF-alpha-producing CD8+ T cells (p=0.029). The percentage of PB/PC was the best variable to differentiate both groups of patients. Baseline values >0.10% closely associated with higher AIAE risk (Odds ratio [OR]: 5.91, 95% CI: 1.83-19.10, p=0.004). When excluding the 12 patients with natalizumab, which decreases blood PB/PC percentages, being the last treatment before alemtuzumab, baseline PB/PC >0.1% even predicted more accurately the risk of AIAEs (OR: 11.67, 95% CI: 2.62-51.89, p=0.0007). The AIAEs+ group continued having high percentages of PB/PC after a year of alemtuzumab treatment (p=0.0058). A PB/PC percentage <0.1% at baseline identifies MS patients at low risk of secondary autoimmunity during alemtuzumab treatment.

The Rare IL22RA2 Signal Peptide Coding Variant rs28385692 Decreases Secretion of IL-22BP Isoform-1, -2 and -3 and Is Associated with Risk for Multiple Sclerosis.

The IL22RA2 locus is associated with risk for multiple sclerosis (MS) but causative variants are yet to be determined. In a single nucleotide polymorphism (SNP) screen of this locus in a Basque population, rs28385692, a rare coding variant substituting Leu for Pro at position 16 emerged significantly (p = 0.02). This variant is located in the signal peptide (SP) shared by the three secreted protein isoforms produced by IL22RA2 (IL-22 binding protein-1(IL-22BPi1), IL-22BPi2 and IL-22BPi3). Genotyping was extended to a Europe-wide case-control dataset and yielded high significance in the full dataset (p = 3.17 × 10-4). Importantly, logistic regression analyses conditioning on the main known MS-associated SNP at this locus, rs17066096, revealed that this association was independent from the primary association signal in the full case-control dataset. In silico analysis predicted both disruption of the alpha helix of the H-region of the SP and decreased hydrophobicity of this region, ultimately affecting the SP cleavage site. We tested the effect of the p.Leu16Pro variant on the secretion of IL-22BPi1, IL-22BPi2 and IL-22BPi3 and observed that the Pro16 risk allele significantly lowers secretion levels of each of the isoforms to around 50%-60% in comparison to the Leu16 reference allele. Thus, our study suggests that genetically coded decreased levels of IL-22BP isoforms are associated with augmented risk for MS

The clinical simulation as a teaching tool. Perception of students degree in Nursing UCAM (San Antonio Catholic University of Murcia-Spain)

Introducción. En el curso académico 2011/2012 se implantó la simulación clínica en el itinerario formativo del grado de enfermería en la UCAM. Se integró dentro de los diferentes Practicum clínicos para introducir nuevas metodologías docentes centradas en el alumno. Objetivos. Conocer la percepción y opinión de los alumnos de 2º y 3º de grado acerca de la simulación clínica. Valorar las propuestas de mejora del alumnado. Identificar las principales críticas hacia la simulación. Metodología. Investigación cualitativa de tipo explotarorio utilizando un cuestionario semiestructurado impreso con preguntas de opinión abiertas para autoentrevista. La población diana fueron alumnos de 2º y 3º de grado en enfermería que cursaron la simulación clínica en el año 2012. El cuestionario fue cumplimentado por los alumnos entre Enero y Junio de 2012. El procesamiento de los datos se realizó clasificando los mismos según categorías/ subcategorías y sometiendo el discurso a un análisis de contenido. Resultados y discusión. La percepción del alumnado es positiva, valorando sobre todo la adquisición de competencias (priorización, refuerzo de conocimientos, confianza, trabajo en equipo, comunicación, rectificación de errores, entrenamiento previo a la práctica real). Los alumnos muestran su disconformidad con el sistema de evaluación y proponen flexibilidad en la asistencia.ABSTRACT Introduction: Clinical simulation was implemented in the training process of the nursing degree in the UCAM. It was integrated within the different clinical Practicum to introduce new teaching methods focused on teaching the students. Objectives: To know the perception and opinion of the students of 2nd and 3rd grade on clinical simulation. To assess students' suggestions for improvement. To identify the major criticisms of the simulation. Methodology: Qualitative study using a semi-structured questionnaire exploratory with printed opinion questions open for self-interview. The target population was students of 2nd and 3rd grade who were enrolled in nursing clinical simulation in 2012. The questionnaire was completed by the students between January and June 2012. The data processing was performed by classifying them according to categories / subcategories and subjecting the speech to a content analysis. Results and discussion: The perception of students is positive, especially when valuing the acquisition of skills (prioritization, strengthening knowledge, confidence, teamwork, communication, error correction, training prior to actual practice). Students show their dissatisfaction with the current assessment system and propose flexibility in attendance

Predicting aggressive multiple sclerosis with intrathecal IgM synthesis among patients with a clinically isolated syndrome

OBJECTIVE: To determine the best method to measure intrathecal immunoglobulin (Ig) M synthesis (ITMS), a biomarker of worse prognosis in multiple sclerosis (MS). We compared the ability for predicting a poor evolution of 4 methods assessing ITMS (IgM oligoclonal bands [OCMBs], lipid-specific OCMBs [LS-OCMBs], Reibergram, and IgM index) in patients with a clinically isolated syndrome (CIS). METHODS: Prospective study with consecutive patients performed at a referral MS center. We used unadjusted and multivariate Cox regressions for predicting a second relapse, Expanded Disability Status Scale (EDSS) scores of 4 and 6, and development of secondary progressive MS (SPMS). RESULTS: A total of 193 patients were included, with a median (interquartile range) age of 31 (25–38) years and a median follow-up of 12.9 years. Among all methods, only OCMB, LS-OCMB, and Reibergram significantly identified patients at risk of some of the pre-established outcomes, being LS-OCMB the technique with the strongest associations. Adjusted hazard ratio (aHR) of LS-OCMB for predicting a second relapse was 2.50 (95% CI 1.72–3.64, p < 0.001). The risk of reaching EDSS scores of 4 and 6 and SPMS was significantly higher among patients with LS-OCMB (aHR 2.96, 95% CI 1.54–5.71, p = 0.001; aHR 4.96, 95% CI 2.22–11.07, p < 0.001; and aHR 2.31, 95% CI 1.08–4.93, p = 0.03, respectively). CONCLUSIONS: ITMS predicts an aggressive MS at disease onset, especially when detected as LS-OCMB. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that lipid-specific IgM oligoclonal bands can predict progression from CIS to MS and a worse disease course over a follow-up of at least 2 years