Clinically-useful serum biomarkers for diagnosis and prognosis of sarcoidosis

Introduction: Sarcoidosis is a complex systemic disease with a silent, long-term evolution, and a heterogeneous clinical presentation. The diagnostic approach is complex with no single diagnostic test that may confirm the disease. Areas covered: A large list of serum biomarkers has been tested during the last 40 years. In this review, we analyse the potential usefulness in the diagnosis and prognosis of sarcoidosis of serum biomarkers classified according to their corresponding cellular source. Expert commentary: Diagnosis of sarcoidosis must always be approached as a multistep process based on a case-by-case integration of clinical, radiological, histological and serological data, none of which being pathognomonic. We found sIL-2R, CRP, SAA and chitotriosidase to be the best markers to confirm sarcoidosis (highest sensitivity), while ACE, gammaglobulins and lysozyme may be more useful for discarding sarcoidosis (highest specificity), taking into account that with the use of a higher cut-off we can increase specificity and with a lower cut-off we can increase sensitivity. Other biomarkers (TNF-a and CCL18) could help to identify patients with an enhanced risk of developing pulmonary fibrosis or progressive disease. The future scenario of the serological diagnostic approach of sarcoidosis will be the use of multi-assays including biomarkers from different cellular sources.Fil: Ramos Casals, Manuel. Sociedad Española de Medicina; España. Instituto Clínic de Medicina y Dermatología; EspañaFil: Retamozo, Maria Soledad. Instituto Clínic de Medicina y Dermatología; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Instituto Modelo de Cardiología Privado; ArgentinaFil: Siso Almirall, Antoni. Instituto de Investigaciones Biomédicas August Pi i Sunyer; EspañaFil: Pérez Alvarez, Roberto. Sociedad Española de Medicina; EspañaFil: Pallarés, Lucio. Sociedad Española de Medicina; España. Sarco GEAS SEMI Study Group; EspañaFil: Brito Zenón, Pilar. Sociedad Española de Medicina; España. Sarco GEAS SEMI Study Group; Españ

Gene variation at immunomodulatory and cell adhesion molecules Loci impacts primary Sjögren's Syndrome

Primary Sjögren's syndrome (pSS) is an autoimmune disease triggered by a combination of environmental and host genetic factors, which results in the focal lymphocytic infiltration of exocrine glands causing eye and mouth dryness. Glandular infiltrates include T and B cell subsets positive for CD5 and/or CD6, two surface scavenger receptors involved in the fine-tuning of intracellular signals mediated by the antigen-specific receptor complex of T (TCR) and B (BCR) cells. Moreover, the epithelial cells of inflamed glands overexpress CD166/ALCAM, a CD6 ligand involved in homo and heterotypic cell adhesion interactions. All this, together with the reported association of functionally relevant single nucleotide polymorphisms (SNPs) of CD5, CD6, and CD166/ALCAM with the risk or prognosis of some immune-mediated inflammatory disorders, led us to investigate similar associations in a local cohort of patients with pSS. The logistic regression analyses of individual SNPs showed the association of CD5 rs2241002T with anti-Ro/La positivity, CD6 rs17824933C with neutropenia, and CD6 rs11230563T with increased leukopenia and neutropenia but decreased peripheral nervous system EULAR Sjögren's syndrome disease activity index (ESSDAI). Further analyses showed the association of haplotypes from CD5 (rs2241002T-rs2229177C) with anemia and thrombocytopenia, CD6 (rs17824933G-rs11230563C-rs12360861G) with cutaneous ESSDAI, and CD166/ALCAM (rs6437585C-rs579565A-rs1044243C and rs6437585C-rs579565G-rs1044243T) with disease susceptibility and several analytical parameters (anti-nuclear antibodies, neurological ESSDAI, and hematologic cytopenias). These results support the relevance of gene variation at loci coding for cell surface receptors involved in the modulation of T and B lymphocyte activation (CD5, CD6) and epithelial-immune cell adhesion (CD166/ALCAM) in modulating the clinical and analytical outcomes in patients with pSS.Peer ReviewedPostprint (published version

Clinical characterization and outcomes of 85 patients with neurosarcoidosis

To analyze the frequency and clinical phenotype of neurosarcoidosis (NS) in one of the largest nationwide cohorts of patients with sarcoidosis reported from southern Europe. NS was evaluated according to the Diagnostic Criteria for Central Nervous System and Peripheral Nervous System Sarcoidosis recently proposed by Stern et al. Pathologic confrmation of granulomatous disease was used to subclassify NS into defnite (confrmation in neurological tissue), probable (confrmation in extraneurological tissue) and possible (no histopathological confrmation of the disease). Of the 1532 patients included in the cohort, 85 (5.5%) fulflled the Stern criteria for NS (49 women, mean age at diagnosis of NS of 47.6 years, 91% White). These patients developed 103 neurological conditions involving the brain (38%), cranial nerves (36%), the meninges (3%), the spinal cord (10%) and the peripheral nerves (14%); no patient had concomitant central and peripheral nerve involvements. In 59 (69%) patients, neurological involvement preceded or was present at the time of diagnosis of the disease. According to the classifcation proposed by Stern et al., 11 (13%) were classifed as a defnite NS, 61 (72%) as a probable NS and the remaining 13 (15%) as a possible NS. In comparison with the systemic phenotype of patients without NS, patients with CNS involvement presented a lower frequency of thoracic involvement (82% vs 93%, q= 0.018), a higher frequency of ocular (27% vs 10%, q< 0.001) and salivary gland (15% vs 4%, q= 0.002) WASOG involvements. In contrast, patients with PNS involvement showed a higher frequency of liver involvement (36% vs 12%, p= 0.02) in comparison with patients without NS. Neurosarcoidosis was identifed in 5.5% of patients. CNS involvement prevails signifcantly over PNS involvement, and both conditions do not overlap in any patient. The systemic phenotype associated to each involvement was clearly diferentiated, and can be helpful not only in the early identifcation of neurological involvement, but also in the systemic evaluation of patients diagnosed with neurosarcoidosis

Gene variation at immunomodulatory and cell adhesion molecules loci impacts primary Sjögren's syndrome

Primary Sjögren's syndrome (pSS) is an autoimmune disease triggered by a combination of environmental and host genetic factors, which results in the focal lymphocytic infiltration of exocrine glands causing eye and mouth dryness. Glandular infiltrates include T and B cell subsets positive for CD5 and/or CD6, two surface scavenger receptors involved in the fine-tuning of intracellular signals mediated by the antigen-specific receptor complex of T (TCR) and B (BCR) cells. Moreover, the epithelial cells of inflamed glands overexpress CD166/ALCAM, a CD6 ligand involved in homo and heterotypic cell adhesion interactions. All this, together with the reported association of functionally relevant single nucleotide polymorphisms (SNPs) of CD5, CD6, and CD166/ALCAM with the risk or prognosis of some immune-mediated inflammatory disorders, led us to investigate similar associations in a local cohort of patients with pSS. The logistic regression analyses of individual SNPs showed the association of CD5 rs2241002T with anti-Ro/La positivity, CD6 rs17824933C with neutropenia, and CD6 rs11230563T with increased leukopenia and neutropenia but decreased peripheral nervous system EULAR Sjögren's syndrome disease activity index (ESSDAI). Further analyses showed the association of haplotypes from CD5 (rs2241002T-rs2229177C) with anemia and thrombocytopenia, CD6 (rs17824933G-rs11230563C-rs12360861G) with cutaneous ESSDAI, and CD166/ALCAM (rs6437585C-rs579565A-rs1044243C and rs6437585C-rs579565G-rs1044243T) with disease susceptibility and several analytical parameters (anti-nuclear antibodies, neurological ESSDAI, and hematologic cytopenias). These results support the relevance of gene variation at loci coding for cell surface receptors involved in the modulation of T and B lymphocyte activation (CD5, CD6) and epithelial-immune cell adhesion (CD166/ALCAM) in modulating the clinical and analytical outcomes in patients with pS

Childhood-onset of primary Sjögren’s syndrome: phenotypic characterization at diagnosis of 158 children

Peer ReviewedPostprint (published version

Cardiovascular Risk in Systemic Autoimmune Diseases: Epigenetic Mechanisms of Immune Regulatory Functions

Autoimmune diseases (AIDs) have been associated with accelerated atherosclerosis (AT) leading to increased cardio- and cerebrovascular disease risk. Traditional risk factors, as well as systemic inflammation mediators, including cytokines, chemokines, proteases, autoantibodies, adhesion receptors, and others, have been implicated in the development of these vascular pathologies. Yet, the characteristics of vasculopathies may significantly differ depending on the underlying disease. In recent years, many new genes and signalling pathways involved in autoimmunity with often overlapping patterns between different disease entities have been further detected. Epigenetics, the control of gene packaging and expression independent of alterations in the DNA sequence, is providing new directions linking genetics and environmental factors. Epigenetic regulatory mechanisms comprise DNA methylation, histone modifications, and microRNA activity, all of which act upon gene and protein expression levels. Recent findings have contributed to our understanding of how epigenetic modifications could influence AID development, not only showing differences between AID patients and healthy controls, but also showing how one disease differs from another and even how the expression of key proteins involved in the development of each disease is regulated

Sarcoidosis

La sarcoidosis es una enfermedad sistémica de etiología desconocida que se caracteriza por el desarrollo de granulomas epiteloides no caseificantes. Los pulmones son los órganos más afectados (>90 % de los casos), seguidos de los ganglios linfáticos, la piel y los ojos. Esta revisión resume las principales manifestaciones clínicas y las opciones actuales de farmacoterapia. Los glucocorticoides son la primera línea de tratamiento para la sarcoidosis. Para los pacientes con las formas más severas de sarcoidosis (que necesitarán glucocorticoides durante largos períodos de tiempo) y para aquellos que son intolerantes o resistentes al tratamiento, se utilizan medicamentos inmunosupresores como agentes ahorradores de glucocorticoides. El manejo de la sarcoidosis extratorácica debe adaptarse al órgano u órgano específico involucrado;sin embargo, hay datos limitados de ensayos controlados para guiar el tratamiento de estos pacientes. La aparición de terapias biológicas ha aumentado el arsenal terapéutico disponible para tratar la sarcoidosis, siendo los agentes anti-TNF monoclonales los más prometedores, pero su uso todavía está limitado por la falta de licencias y costos.Sarcoidosis is a systemic disease of unknown etiology characterized by the development of non-caseating epitheloid granulomas. The lungs are the most commonly involved organ (>90% of cases), followed by the lymph nodes, the skin, and the eyes. Areas covered: This review summarizes current pharmacotherapy options and future directions for the development of new therapies. Glucocorticoids are the first-line therapy for sarcoidosis. For patients with the most severe forms of sarcoidosis (who will need glucocorticoids for long periods) and for those intolerant or refractory, immunosuppressive drugs are used as sparing agents. The management of extrathoracic sarcoidosis must be tailored to the specific organ or organs involved;however, there is limited data from controlled trials to guide the treatment of these patients. The emergence of biological therapies has increased the therapeutic armamentarium available to treat sarcoidosis, with monoclonal anti-TNF agents being the most promising, but their use is still limited by a lack of licensing and costsFil: Retamozo, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; ArgentinaFil: Brito Zeron, Pilar. Hospital Cima-sanitas; EspañaFil: Pérez Álvarez, Roberto. Sociedad Española de Medicina Interna; EspañaFil: Achad, Mario Oscar. Universidad Nacional de Córdoba; ArgentinaFil: Pallarés, Lucio. Sociedad Española de Medicina Interna; EspañaFil: Cuestas, Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Ramos Casals, Manuel. Sociedad Española de Medicina Interna; Españ

Zarzuela - Ópera - Ballet

Agua, azucarillos y aguardiente de Federico Chueca i llibret de Miguel Ramos Carrión; La viejecita de Manuel Fernández Caballero i llibret de Miguel EchegarayDe cada obra s'ha digitalitzat un programa sencer. De la resta s'han digitalitzat les parts que són diferents.Director Ramón Gorg