Biomarcadores predictivos en esclerosis múltiple

La esclerosis múltiple (EM) es una enfermedad autoinmune crónica del sistema nervioso central (SNC) en la que participan en distinto grado mecanismos de inflamación, desmielinización, daño axonal, neurodegeneración, gliosis y remielinización. La EM se clasifica en tres formas clínicas predominantes: remitenterecurrente (EMRR), primaria progresiva (EMPP) y secundaria progresiva (EMSP). A día de hoy, en ausencia de un biomarcador específico, el diagnóstico de EM suele retrasarse al requerir la aparición de un segundo brote clínico o una confirmación de diseminación en espacio y tiempo de las lesiones por técnicas de neuroimagen para poder confirmar el diagnóstico. Uno de los mayores retos actuales es identificar biomarcadores capaces de reconocer y predecir el curso de la enfermedad en el paciente individual, que podría permitir el uso de estrategias terapéuticas más personalizadas, sobre todo en el caso de pacientes con formas progresivas, para los que actualmente no hay terapia disponible. Basándonos en resultados previos que nos permitieron definir un panel de 12 analitos con capacidad diagnóstica y pronóstica, hemos llevado a cabo un estudio transversal al inicio de las manifestaciones neurológicas para validar la utilidad clínica del mismo. En el estudio se han identificado y validado una serie de biomarcadores con elevado poder diagnóstico y pronóstico, que proporcionan por un lado una herramienta de utilidad en la práctica clínica habitual, y por otro lado permiten explorar y conocer en mayor profundidad la fisiopatología de la enfermedad y las diferencias entre las fases progresivas y las predominantemente inflamatorias..

Jardins per a la salut

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia. Assignatura: Botànica farmacèutica. Curs: 2014-2015. Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són el recull de les fitxes botàniques de 128 espècies presents en el Jardí Ferran Soldevila de l’Edifici Històric de la UB. Els treballs han estat realitzats manera individual per part dels estudiants dels grups M-3 i T-1 de l’assignatura Botànica Farmacèutica durant els mesos de febrer a maig del curs 2014-15 com a resultat final del Projecte d’Innovació Docent «Jardins per a la salut: aprenentatge servei a Botànica farmacèutica» (codi 2014PID-UB/054). Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pels professors de l’assignatura. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica. També s’ha pretès motivar els estudiants a través del retorn de part del seu esforç a la societat a través d’una experiència d’Aprenentatge-Servei, deixant disponible finalment el treball dels estudiants per a poder ser consultable a través d’una Web pública amb la possibilitat de poder-ho fer in-situ en el propi jardí mitjançant codis QR amb un smartphone

Profiling of Canonical and Non-Traditional Cytokine Levels in Interferon-β-Treated Relapsing–Remitting-Multiple Sclerosis Patients

BackgroundMultiple sclerosis (MS) is a chronic, progressive autoimmune disease of the central nervous system in which inflammation plays a key role in the induction, development, and progression. Most of the MS patients present with relapsing–remitting (RR) form, characterized by flare-ups followed by periods of recovery. Many inflammatory and anti-inflammatory cytokines have been proposed as backers in MS pathogenesis, and the balance between these differing cytokines can regulate MS severity. Interferon (IFN)-β, a current disease-modifying therapy for MS, has demonstrated beneficial effects in reducing disease severity in MS patients. However, its immunoregulatory and anti-inflammatory actions in MS are not wholly understood. The aim of the study was to define, in clinically stable patients with RR-MS, the serum concentration of several cytokines, canonical or not, and their modulation by IFN-β therapy.MethodsRelapsing–remitting-MS patients were enrolled and diagnosed according to revised Mc Donald Diagnostic Criteria. A set of cytokines [including non-canonical neurotransmitter acetylcholine (ACh) and adipokines] and B-cell differentiation molecules, as potential biomarkers, were evaluated in 30 non-treated RR-MS patients compared to 30 IFN-β-treated MS patients and 30 age, gender, and body mass index-matched healthy controls (HC).ResultsNaïve MS patients showed significantly higher levels of interleukin (IL)-1β, IL-12/IL-23p40, IL-18, high-mobility group box protein-1, and IL-18 binding protein (IL-18BP) than MS-treated patients (p < 0.001 for all) and HC (p < 0.01). IFN-β therapy has significantly downmodulated IL-1β, IL-12/IL-23p40, IL-18 to normal levels (p < 0.001), whereas it has decreased IL-18BP (p < 0.001). ACh was significantly higher in the IFN-β-treated than HC and non-treated MS patients (p < 0.001). No significant differences were observed either in adipokines concentration or in B-cell-associated molecules among the three study groups.ConclusionAlthough more experimental evidence are required, we speculate that the efficacy of treatment of MS with IFN-β is mediated, at least in part, by its ability to work on several levels to slow down the disease progression. Proposed actions include the modulation of IL-1–inflammasome axis and modulation of ACh, B-cell activating factor/a proliferation-inducing ligand system, and several adipokines

Multiple Sclerosis: Where do we go from here?

Multiple sclerosis (MS) is the most common cause of neurological disability in young populations after trauma and represents a significant personal, social, and economic public health burden. The clinical course and response of MS to therapy is highly heterogeneous, but most patients progress from a relapsing-remitting disease course, in which patients may respond to immunomodulatory drugs, to a steady progression and neurodegeneration that is unresponsive to any currently available treatment. In the last few years, novel disease-modifying therapies for MS have become available but the aetiology of the disease remains an enigma. The search for clinical biomarkers that are able to stratify MS patients and allow the personalisation of treatment strategies, has developed greatly in recent years though only a few have been integrated into routine clinical practice

Intravenous immunoglobulins promote an expansion of monocytic myeloid-derived suppressor cells (MDSC) in CVID patients

13 p.-4 fig.Common variable immunodeficiency disorders (CVID), the most common primary immune deficiency, includes heterogeneous syndromes characterized by hypogammaglobulinemia and impaired antibody responses. CVID patients frequently suffer from recurrent infections and inflammatory conditions. Currently, immunoglobulin replacement therapy (IgRT) is the first-line treatment to prevent infections and aminorate immune alterations in CVID patients. Intravenous Immunoglobulin (IVIg), a preparation of highly purified poly-specific IgG, is used for treatment of immunodeficiencies as well as for autoimmune and inflammatory disorders, as IVIg exerts immunoregulatory and anti-inflammatory actions on innate and adaptive immune cells. To determine the mechanism of action of IVIg in CVID in vivo, we determined the effect of IVIg infusion on the transcriptome of peripheral blood mononuclear cells from CVID patients, and found that peripheral blood monocytes are primary targets of IVIg in vivo, and that IVIg triggers the acquisition of an anti-inflammatory gene profile in human monocytes. Moreover, IVIg altered the relative proportions of peripheral blood monocyte subsets and enhanced the proportion of CD14+ cells with a transcriptional, phenotypic, and functional profile that resembles that of monocytic myeloid-derived suppressor cells (MDSC). Therefore, our results indicate that CD14 + MDSC-like cells might contribute to the immunoregulatory effects of IVIg in CVID and other inflammatory disorders.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by grants from Ministerio de Economía y Competitividad (SAF2017-83785-R)to MAV and ALC, Grant 201619.31 from Fundación La Marató/TV3 to ALC, and Red de Investigación en Enfermedades Reumáticas(RIER, RD16/0012/0007), and cofinanced by the European Regional Development Fund “A way to achieve Europe” (ERDF), to ALC, and grant 19/284-E from Instituto de Salud Carlos III (ISCIII) to SSR. MS-F was funded by a Formación de Personal Investigador predoctoral fellowship from MINECO (grant PRE2018-083396).Peer reviewe

IP10/CXCL10 and MCP-1/CCL2 levels were higher in MS patients with good response to IFN-β treatment.

<p>Long-term IFN-β treated RR-MS patients (RESPONDERS, n = 20) presented with higher circulating levels of IP10/CXCL10 and MCP-1/CCL2 than non responders to IFN-β (NON RESPONDERS, n = 13). Mann—Whitney statistical test was used for calculation of the reported p-value; median values are represented by a gray bar; individual dots indicate single donor values.</p

HGF, Eotaxin/CCL11, MCP-1/CCL2, Rantes/CCL5, EGF and MIP-1β/CCL4 comparison in the test and validation cohorts.

<p>Mann—Whitney statistical test was used for calculation of the reported p-value between RR-MS vs Progressive MS; RR-MS = Relapsing-Remitting MS patients. Note that the Relapsing-remitting group comprises the clinical groups: RR-MS Remission, RR-MS Active, RESPONDERS, NON RESPONDERS and RELAPSES. The Progressive group comprises Secondary (SP-MS) and Primary-progressive patients.</p><p>Results are given as Median value (IQR1–3). Statistical significance is marked as:</p><p>*p<0.05;</p><p>**p<0.01;</p><p>***p<0.001.</p><p>^# p = 0.06 (trend).</p><p>HGF, Eotaxin/CCL11, MCP-1/CCL2, Rantes/CCL5, EGF and MIP-1β/CCL4 comparison in the test and validation cohorts.</p

FGFb levels were significantly decreased in primary progressive MS patients.

<p>Comparison of the plasma levels of FGFb between primary progressive MS patients (PP-MS, n = 18) with respect to healthy controls (HC, n = 36), to secondary progressive MS patients (SP-MS, n = 31) and to patients undergoing a clinical relapse (RELAPSES, n = 11). Mann—Whitney statistical test was used for calculation of the reported p-value; median values are represented by a gray bar; individual dots indicate single donor values.</p

Different plasma levels of HGF, Eotaxin/CCL11, MCP-1/CCL2 and Rantes/CCL5 in MS clinical forms.

<p>Plasma levels of HGF, Eotaxin/CCL11, MCP-1/CCL2 and Rantes/CCL5 were lower in relapsing-remitting MS than in the progressive MS patients. Comparison of the plasma levels of HGF, Eotaxin/CCL11 (top dot plots), MCP-1/CCL2 and Rantes/CCL5 (lower dot plots) in relapsing-remitting (RR-MS, n = 80) and in the group of progressive MS (n = 49) patients. Mann—Whitney statistical test was used for calculation of the reported p-value; median values are represented by a gray bar; individual dots indicate single donor values. Note that the Relapsing-remitting group comprises the clinical groups: RR-MS Remission, RR-MS Active, RESPONDERS, NON RESPONDERS and RELAPSES. The Progressive group comprises Secondary (SP-MS) and Primary-progressive patients.</p

Logistic regression with HGF, Eotaxin/CCL11, EGF and MIP-1β/CCL4 as independent variables and the clinical MS-forms (Relapsing-Remitting vs Progressive MS) as the dichotomous target variable.

<p>O.R. (odds ratio); C.I. (95%) Interval of confidence.</p><p>Logistic regression with HGF, Eotaxin/CCL11, EGF and MIP-1β/CCL4 as independent variables and the clinical MS-forms (Relapsing-Remitting vs Progressive MS) as the dichotomous target variable.</p