LECTURAS CIENTÍFICAS

  • Effects of pre-analytical heat treatment in factor VIII (FVIII) inhibitor assays on FVIII antibody levels.
    Effects of pre-analytical heat treatment in factor VIII (FVIII) inhibitor assays on FVIII antibody levels. Haemophilia. 2018 Feb 20;: Authors: Boylan B, Miller CH Abstract INTRODUCTION: The use of pre-analytical heat treatment (PHT) with the Nijmegen-Bethesda assay (NBA) for inhibitors to factor VIII (FVIII) can remove/destroy infused or endogenous FVIII from patient plasma samples, allowing testing of recently infused patients with haemophilia. Two PHT methods have been described as follows: heating to 56°C for 30 minutes and heating to 58°C for 90 minutes. Data examining the effects of PHT on anti-FVIII IgG4 , the antibodies known to correlate most closely with the presence of FVIII inhibitors, are limited. AIM: To assess the effect of PHT on the levels of detectable anti-FVIII IgG4 . METHODS: Nijmegen-Bethesda assay-positive specimens were incubated at 56, 58 or 60°C for 90 minutes, and anti-FVIII IgG4 was measured by fluorescence immunoassay (FLI) at 30-minute intervals. The effects of PHT on the ability of recombinant FVIII (rFVIII) to inhibit detection of patient antibodies by FLI was also examined to assess the stability of rFVIII under the various PHT conditions tested. RESULTS: Levels of anti-FVIII IgG4 showed little change following incubations at 56°C (mean 101% of original value at 30 minutes and 100% at 60 minutes) but decreased upon exposure to 58°C (mean 85% at 30 minutes and 66% at 60 minutes). In addition, heating to 56°C effectively decreased the ability of rFVIII to block antibody binding compared to unheated rFVIII. CONCLUSION: The optimal temperature for PHT in the FVIII NBA is 56°C. Higher temperatures… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-21
  • Clinical and pathophysiological aspects of type 1 autoimmune pancreatitis.
    Related ArticlesClinical and pathophysiological aspects of type 1 autoimmune pancreatitis. J Gastroenterol. 2018 Feb 19;: Authors: Uchida K, Okazaki K Abstract In 1995, Yoshida and colleagues proposed the concept of "autoimmune pancreatitis" (AIP), which has recently been recognized as a new pancreatic inflammatory disease. Recent studies have suggested the existence of two subtypes of AIP: type 1, which involves immunoglobulin G4 (IgG4) and is the pancreatic manifestation of IgG4-related disease (IgG4-RD); and type 2, which is characterized by granulocytic epithelial lesions. Type 2 AIP is thought to be rare in Japan. Type 1 AIP is characterized by increased serum IgG4 concentrations, lymphoplasmacytic infiltrations, storiform fibrosis, and obliterative phlebitis. However, although type 1 AIP has become increasingly recognized, many clinical and basic issues remain to be solved. This review provides an overview of the recent clinical and basic knowledge of type 1 AIP.PMID: 29460239 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-21
  • MRI features of primary hepatic lymphoma.
    Related ArticlesMRI features of primary hepatic lymphoma. Abdom Radiol (NY). 2018 Feb 19;: Authors: Colagrande S, Calistri L, Grazzini G, Nardi C, Busoni S, Morana G, Grazioli L Abstract PURPOSE: Our retrospective study sought to describe the spectrum of magnetic resonance imaging (MRI) features of primary hepatic lymphoma (PHL) by analyzing its morphological aspects, signal intensity before and after contrast agent (CA) administration, and diffusion-weighted imaging (DwI) with the apparent diffusion coefficient (ADC) values. METHODS: A retrospective analysis was conducted on 25 patients with pathologically proven PHL who underwent MRI between January 2011 and December 2016. For the evaluation of the ADC, we used a control group of 87 patients (22 with hepatocellular carcinoma, 15 with cholangiocellular carcinoma, 23 with liver metastasis, 22 with focal nodular hyperplasia, and 5 with adenoma). Two radiologists evaluated the morphological features, the signal intensity before and after CA administration, and the DwI. The sensitivity and specificity of the ADC values in distinguishing the PHL lesions from other hepatic lesions were calculated by analyzing the receiver operating characteristic (ROC) curves. RESULTS: Twenty-one patients had non-Hodgkin's lymphoma (18 had diffuse large B-cell lymphoma and three had mucosa-associated lymphoid tissue) and four had Hodgkin's lymphoma (nodular sclerosis). The PHL had a variable morphologic distribution (17 focal mass and eight multiple nodules) and mainly an insinuative growth (24/25). Usually, PHL was usually hypointense on the T1-weighted images (23/25) and hyperintense on the T2-weighted images (21/25); non-specific dynamic enhancement was found after CA administration, but in the hepatobiliary phase,… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-21
  • Time Is Cerebellum.
    Related ArticlesTime Is Cerebellum. Cerebellum. 2018 Feb 19;: Authors: Mitoma H, Manto M, Hampe CS Abstract The cerebellum characteristically has the capacity to compensate for and restore lost functions. These compensatory/restorative properties are explained by an abundant synaptic plasticity and the convergence of multimodal central and peripheral signals. In addition, extra-cerebellar structures contribute also to the recovery after a cerebellar injury. Clinically, some patients show remarkable improvement of severe ataxic symptoms associated with trauma, stroke, metabolism, or immune-mediated cerebellar ataxia (IMCA, e.g., multiple sclerosis, paraneoplastic cerebellar degeneration, gluten ataxia, anti-GAD65 antibody-associated cerebellar ataxia). However, extension of a cerebellar lesion can impact upon the fourth ventricle or the brainstem, either by direct or indirect mechanisms, leading to serious complications. Moreover, cerebellar reserve itself is affected by advanced cell loss and, at some point of disease progression, deficits become irreversible. Such phase transition from a treatable/restorable state (the reserve is still sufficient) to an untreatable state (the reserve is severely affected) is a loss of therapeutic opportunity, highlighting the need for early treatment during the restorable stage. Based on the motto of "Time is Brain," a warning that stresses the importance of early therapeutic intervention in ischemic diseases, we propose "Time is Cerebellum" as a principle in the management of patients with cerebellar diseases, especially immune ataxias whose complexity often delay the therapeutic intervention. Indeed, this concept should not be restricted to ischemic cerebellar diseases. We argue that every effort should be made to reduce the diagnostic delay and to initiate early… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-21
  • Rapidly progressive diffuse systemic sclerosis after local vitamins A, D and E complex injections: literature review and report of two cases.
    Related ArticlesRapidly progressive diffuse systemic sclerosis after local vitamins A, D and E complex injections: literature review and report of two cases. Immunol Res. 2017 Feb;65(1):285-292 Authors: Balbi GGM, Montes RA, Vilela VS, Andrade MAB, Nóbrega MM, Azulay-Abulafia L, da Silva RS, Klumb EM, Levy RA Abstract The term autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) or Shoenfeld's syndrome refers to a wide group of immune-mediated diseases triggered by external agents. Several substances, such as vaccine adjuvants, squalene and silicone implants, are implied in the pathogenesis of ASIA syndrome. Treatment and prognosis of this complex condition are not completely known due to lack of good quality evidence. After a brief introductory literature review on ASIA, we report here two cases of patients that developed rapidly progressive systemic sclerosis clinical features after multiple intramuscular local injections of a substance recommended by a non-medical professional called ADE. ADE is an oily vitamin complex for veterinary use, and it was used in these cases for cosmetic muscular definition and enhancement purpose. To our knowledge, this is the first paper to describe the relation between injections of ADE and the development of ASIA with severe systemic sclerosis phenotype. Further investigation is needed to better understand the pathophysiology and to provide the basis for the treatment of this condition.PMID: 27515982 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-21
  • The Immunologic Paradoxes of IgG4-Related Disease.
    Related ArticlesThe Immunologic Paradoxes of IgG4-Related Disease. Clin Rev Allergy Immunol. 2018 Feb 19;: Authors: Xiao X, Lian M, Zhang W, Eric Gershwin M, Ma X Abstract IgG4-related disease (IgG4-RD), which usually occurs in middle-aged and elderly men, is a newly recognized fibroinflammatory condition characterized by swelling and sclerosis of involved organs, increased IgG4-positive plasma cell infiltration in lesions, and elevated IgG4 concentration in serum. Despite growing interest in the research, the pathophysiological mechanism remains elusive. Most IgG4-RD patients respond well to steroid therapy initially, but recurrent and refractory cases are common, especially in advanced fibrotic stage. Recent studies have documented the heterogeneity of the B cell lineages, which suggests their multiple functions in IgG4-RD beyond IgG4 production, such as cytokine secretion, antigen presentation, autoantibody production, and modulation of T and B cell interactions. Thus, a critical balance exists between pathogenic and regulatory B subsets to prevent immunopathology. A prompt response to B cell depletion therapy reported in recent cases strongly suggests the imbalance within B cell lineages in IgG4-RD. A more precise understanding of the pathogenesis of IgG4-RD will open up new perspectives for therapeutic strategy. With a particular emphasis on the novel B cell-targeted therapeutic strategies, this review highlights the immunologic features of IgG4-RD and the possible roles of B cell lineages in the pathogenesis of IgG4-RD.PMID: 29460058 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-21
  • A Comparison of Human Natural Monoclonal Antibodies and Aptamer Conjugates for Promotion of CNS Remyelination: Where Are We Now and What Comes Next?
    A Comparison of Human Natural Monoclonal Antibodies and Aptamer Conjugates for Promotion of CNS Remyelination: Where Are We Now and What Comes Next? Expert Opin Biol Ther. 2018 Feb 20;: Authors: Perwein MK, Smestad JA, Warrington AE, Heider RM, Kaczor MW, Maher LJ, Wootla B, Kunbaz A, Rodriguez M Abstract INTRODUCTION: Multiple sclerosis (MS) is a chronic and progressive inflammatory demyelinating disease of the human central nervous system (CNS) and is the most common disabling neurological condition in young adults, resulting in severe neurological defects. No curative or long-term progression-inhibiting therapy has yet been developed. However, recent investigation has revealed potential strategies that do not merely modulate potentially pathogenic autoimmune responses, but stimulate remyelination within CNS lesions. Areas Covered: We discuss the history and development of natural human IgM-isotype immunoglobulins (HIgMs) and recently-identified aptamer-conjugates that have been shown to enhance endogenous myelin repair in animal models of demyelination by acting on myelin-producing oligodendrocytes (OLs) or oligodendrocyte progenitor cells (OPCs) within CNS lesions. We also discuss future development aims and applications for these important novel technologies. Expert Opinion: Aptamer conjugate Myaptavin-3064 and recombinant human IgM-isotype antibody rHIgM22 regenerate CNS myelin, thereby reducing axonal degeneration and offering the potential of recovery from MS relapses, reversal of disability and prevention of disease progression. Advancement of these technologies into the clinic for MS treatment is therefore a top priority. It remains unclear to what extent the therapeutic modalities of remyelinating antibodies and aptamers may synergize with other currently-approved therapies to yield enhanced therapeutic effects.PMID:… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-21
  • Guillain-Barré syndrome in Colombia: where do we stand now?
    Related ArticlesGuillain-Barré syndrome in Colombia: where do we stand now? Immunol Res. 2017 Feb;65(1):72-81 Authors: Mahecha MP, Ojeda E, Vega DA, Sarmiento-Monroy JC, Anaya JM Abstract Guillain-Barré syndrome (GBS) is a rapid-onset muscle weakness disease caused by the immune-mediated damage of the peripheral nervous system. Since there is an increase incidence of GBS cases in Latin America, particularly in Colombia, and most of them are currently preceded by Zika virus (ZIKV) infection, we aimed to assess the available evidence of the disease in Colombia through a systematic literature review. Out of 51 screened abstracts, only 16 corresponded to articles that met inclusion criteria, of which 15 were case reports or case series. A total of 796 cases of GBS were reported in the included articles. The majority of patients were males (66.8 %) and younger than 50 years old (94 %). An infectious disease before the onset of GBS was registered in 31 % of patients, with gastrointestinal or respiratory symptoms being the most frequently observed. In those cases in which electrodiagnostic tests were performed, the most common subphenotype was acute inflammatory demyelinating polyneuropathy (17 %). Death was reported in 15 % of patients. Data regarding GBS in Colombia is scant and heterogeneous. Taking into account the burden of the disease and the recent rise of GBS cases associated with ZIKV, a careful patient evaluation and a systematic collection of data are warranted. A form to data gathering is proposed.PMID: 27421717 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-21
  • Guillain-Barré syndrome in France: a nationwide epidemiological analysis based on hospital discharge data (2008-2013).
    Related ArticlesGuillain-Barré syndrome in France: a nationwide epidemiological analysis based on hospital discharge data (2008-2013). J Peripher Nerv Syst. 2017 Mar;22(1):51-58 Authors: Delannoy A, Rudant J, Chaignot C, Bolgert F, Mikaeloff Y, Weill A Abstract Guillain-Barré syndrome (GBS) is potentially life threatening and typically occurs after an infection. No detailed information is available concerning the epidemiological characteristics of GBS in France. We estimated age- and sex-specific incidence rates (IRs) based on a French nationwide hospital discharge database. All patients hospitalized for GBS between 2008 and 2013 were identified by International Classification of Diseases-10 code G61.0 as principal diagnosis. Patients previously hospitalized for GBS in 2006 and 2007 were excluded. Sensitivity analyses were performed by considering alternative case definitions, based on more restrictive sets of codes. A total of 9,391 patients were identified, leading to an overall crude IR of 2.42 per 100,000 person-years (world standardized IR = 2.00). IRs increased with age, reaching a peak in the 70-79-year age group. IR was 46% higher in men than in women, and 44% higher in winter than in summer. In children, the highest IR was observed at the age of 2 years. These patterns were not modified by the use of alternative case definitions. This French nationwide study showed similar GBS epidemiological patterns in adults to those reported in other countries. We also report a childhood incidence peak around the age of 2 years, as previously observed in Latin American and Chinese populations.PMID: 27991707 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-21
  • Inhibition of complement in Guillain-Barré syndrome: the ICA-GBS study.
    Related ArticlesInhibition of complement in Guillain-Barré syndrome: the ICA-GBS study. J Peripher Nerv Syst. 2017 Mar;22(1):4-12 Authors: Davidson AI, Halstead SK, Goodfellow JA, Chavada G, Mallik A, Overell J, Lunn MP, McConnachie A, van Doorn P, Willison HJ Abstract The outcome of Guillain-Barré syndrome (GBS) remains unchanged since plasma exchange and intravenous immunoglobulin (IVIg) were introduced over 20 years ago. Pathogenesis studies on GBS have identified the terminal component of complement cascade as a key disease mediator and therapeutic target. We report the first use of terminal complement pathway inhibition with eculizumab in humans with GBS. In a randomised, double-blind, placebo-controlled trial, 28 subjects eligible on the basis of GBS disability grade of at least 3 were screened, of whom 8 (29%) were randomised. Five received eculizumab for 4 weeks, alongside standard IVIg treatment. The safety outcomes, monitored via adverse events capture, showed eculizumab to be well-tolerated and safe when administered in conjunction with IVIg. Primary and secondary efficacy outcomes in the form of GBS disability scores (GBS DS), MRC sum scores, Rasch overall disability scores, and overall neuropathy limitation scores are reported descriptively. For the primary efficacy outcome at 4 weeks after recruitment, two of two placebo- and two of five eculizumab-treated subjects had improved by one or more grades on the GBS DS. Although the small sample size precludes a statistically meaningful analysis, these pilot data indicate further studies on complement inhibition in GBS are warranted.PMID: 27801990 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-21
  • Guillain-Barré Syndrome.
    Related ArticlesGuillain-Barré Syndrome. Neurocrit Care. 2016 10;25(2):288-92 Authors: Wijdicks EF PMID: 27660176 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-21
  • Myasthenia Gravis with Muscle-Specific Tyrosine Kinase (MuSK) Antibodies- A Narrative Review.
    Myasthenia Gravis with Muscle-Specific Tyrosine Kinase (MuSK) Antibodies- A Narrative Review. Muscle Nerve. 2018 Feb 20;: Authors: Morren J, Li Y Abstract Growing evidence provides new insights about myasthenia gravis with antibodies against muscle-specific tyrosine kinase (MuSK-MG) including its pathogenesis, clinical and electrophysiological manifestations, and treatment. Data now support the presence of both presynaptic and postsynaptic dysfunction in MuSK-MG. This is one of many key differences between MuSK-MG and acetylcholine receptor antibody-MG (AChR-MG), especially as it pertains to potential therapeutic implications. In comparison to AChR-MG, MuSK-MG is generally more refractory to treatment. However, with MuSK-MG being better understood and more readily recognized today, there are more reports of a relatively benign course. The most effective immunotherapies for MuSK-MG are corticosteroids, plasmapheresis and rituximab. With appropriate therapy, most MuSK-MG patients achieve minimal manifestation status or better on the post-intervention status outlined by Myasthenia Gravis Foundation of America. A minority of patients remain refractory to treatment, and optimal management for this group remains a considerable challenge. This article is protected by copyright. All rights reserved.PMID: 29461627 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-21
  • Journal Club: MRI reveals acute inflammation in cortical lesions during early MS.
    Related ArticlesJournal Club: MRI reveals acute inflammation in cortical lesions during early MS. Neurology. 2018 Feb 20;90(8):e724-e726 Authors: Bateman EM, Schleicher WE, Smith EJ, Sweet DR, Gaudet AD Abstract Early multiple sclerosis is characterized by immune-associated demyelination of CNS axons. In a recent Neurology® article, Maranzano et al. evaluated MRI scans of patients with early multiple sclerosis to study the evolution of leukocortical lesions. Their novel data suggest that acute inflammation after blood-brain barrier leakage may contribute to gray matter cortical lesions in early multiple sclerosis.PMID: 29459454 [PubMed - in process] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-21
  • The value of oligoclonal bands in the multiple sclerosis diagnostic criteria.
    The value of oligoclonal bands in the multiple sclerosis diagnostic criteria. Brain. 2018 Feb 16;: Authors: Arrambide G, Tintore M, Espejo C, Auger C, Castillo M, Río J, Castilló J, Vidal-Jordana A, Galán I, Nos C, Mitjana R, Mulero P, de Barros A, Rodríguez-Acevedo B, Midaglia L, Sastre-Garriga J, Rovira A, Comabella M, Montalban X Abstract The presence of oligoclonal bands in clinically isolated syndromes is an independent risk factor for developing multiple sclerosis and has been largely excluded from the more recent multiple sclerosis diagnostic criteria. Therefore, our objective was to explore the value of oligoclonal bands in the context of the 2010 McDonald criteria, especially in patients fulfilling exclusively dissemination in space at baseline. For this purpose, we selected 566 patients from a clinically isolated syndrome inception cohort who had IgG oligoclonal bands determination and sufficient data on baseline brain MRI to assess dissemination in space and time. We excluded the cases already fulfilling both dissemination in space and time and divided the remaining 398 into 'no dissemination in space and time' (n = 218), 'dissemination in space' (n = 164) and 'dissemination in time' (n = 16). We assessed Cox proportional hazards regression models with 2010 McDonald as the outcome, using 'no dissemination in space and time' with 0 lesions and negative oligoclonal bands as the reference for different subgroups according to oligoclonal bands status (positive/negative). To assess the diagnostic properties, we selected cases with a follow-up ≥3 years or fulfilling 2010 McDonald within 3 years of… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-21
  • Changes in the axo-glial junctions of the optic nerves of cuprizone-treated mice.
    Related ArticlesChanges in the axo-glial junctions of the optic nerves of cuprizone-treated mice. Histochem Cell Biol. 2018 Feb 19;: Authors: Kojima W, Hayashi K Abstract Demyelination induced by cuprizone in mice has served a useful model system for the study of demyelinating diseases, such as multiple sclerosis. Severity of demyelination by cuprizone, however, varies across different regions of the central nervous system; the corpus callosum is sensitive, while the optic nerves are resistant. Here, we investigated the effects of cuprizone on optic nerves, focusing on the axo-glial junctions. Immunostaining for sodium channels, contactin-associated protein, neurofascins, and potassium channels revealed that there were no massive changes in the density and morphology of the axo-glial junctions in cuprizone-treated optic nerves. However, when we counted the number of incomplete junctional complexes, we observed increased numbers of isolated paranodes. These isolated paranodes were immunopositive for both axonal and glial membrane proteins, indicating that they were the contact sites between axons and glia. These were not associated with sodium channels or potassium channels, suggesting the absence of physiological functions. When teased axons from cuprizone-treated optic nerves were immunostained, the isolated paranodes were found at the internode region of the myelin. From these observations, we conclude that cuprizone induces new contacts between axons and myelins at the internode region.PMID: 29460173 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-21
  • An International, Multi-Specialty Validation Study of the IgG4-Related Disease Responder Index.
    Related ArticlesAn International, Multi-Specialty Validation Study of the IgG4-Related Disease Responder Index. Arthritis Care Res (Hoboken). 2018 Feb 18;: Authors: Wallace ZS, Khosroshahi A, Carruthers MD, Perugino CA, Choi H, Campochiaro C, Culver EL, Cortazar F, Dellatorre E, Ebbo M, Fernandes A, Frulloni L, Hart P, Karadag O, Kawa S, Kawano M, Kim MH, Lanzillotta M, Matsui S, Okazaki K, Ryu JH, Saeki T, Schleinitz N, Tanasa P, Umehara H, Webster G, Zhang W, Stone JH Abstract OBJECTIVE: IgG4-related disease (IgG4-RD) can cause fibro-inflammatory lesions in nearly any organ, leading to organ dysfunction and failure. The IgG4-RD Responder Index (RI) was developed to help investigators assess the efficacy of treatment in a structured manner. We sought to validate the RI in a multi-national investigation. METHODS: The RI guides investigators through assessments of disease activity and damage in 25 domains, incorporating higher weights for disease manifestations that require treatment urgently or that worsen despite treatment. After a training exercise, investigators reviewed 12 written IgG4-RD vignettes (mean length: 279 words, range: 76-511 words) based upon real patients. Investigators calculated both an RI score as well as a physician global assessment (PGA) for each vignette. Three investigators used the RI on fifteen patients followed over serial visits after treatment. We assessed inter- and intra-rater reliability, precision, validity, and responsiveness. RESULTS: Twenty-six physician-investigators included representatives from 6 specialties and 9 countries. The inter-rater and intra-rater reliabilities of the RI were strong (0.88 and 0.69, respectively) and superior to those of the PGA. Correlations (construct… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-20
  • Concurrent eosinophilia and IgG4-related disease in a child: A case report and review of the literature.
    Related ArticlesConcurrent eosinophilia and IgG4-related disease in a child: A case report and review of the literature. Exp Ther Med. 2018 Mar;15(3):2739-2748 Authors: Chen C, Chen K, Huang X, Wang K, Qian S Abstract The current study presents the case of a 9-year-old Chinese boy who presented with eosinophilia and elevated serum levels of immunoglobulin G4 (IgG4). A bone marrow puncture identified an elevated eosinophil rate of 23% (normal range, <5%), which indicated eosinophilia. However, gene analysis, fluorescent in situ hybridization and other examinations, including bone marrow aspiration, blood routine, auto-antibody tests and parasitic and allergens screening, contradicted a diagnosis of secondary or clonal eosinophilia. Furthermore, the patient exhibited multiple lymph node swelling and a lymph biopsy strongly indicted a pathological diagnosis of IgG4-related disease (IgG4-RD). His peripheral blood flow cytometry confirmed an elevated count of plasmablasts, which is specific to IgG4-RD. The patient responded well to therapy with prednisone and remained healthy in all follow-ups. By taking all these factors into consideration, the boy was diagnosed with IgG4-RD. It is difficult to distinguish IgG4-RD from hypereosinophilic syndrome and the potential association between the two remains unclear. However, the present case study serves as a reminder that IgG4-RD may occur in children and medical professionals should not neglect this possibility.PMID: 29456677 [PubMed] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-20
  • The Use of Biomarkers to Predict Aero-Allergen and Food Immunotherapy Responses.
    Related ArticlesThe Use of Biomarkers to Predict Aero-Allergen and Food Immunotherapy Responses. Clin Rev Allergy Immunol. 2018 Feb 17;: Authors: Sindher SB, Long A, Acharya S, Sampath V, Nadeau KC Abstract The incidence of allergic conditions has continued to rise over the past several decades, with a growing body of research dedicated toward the treatment of such conditions. By driving a complex range of changes in the underlying immune response, immunotherapy is the only therapy that modulates the immune system with long-term effects and is presently utilized for the treatment of several atopic conditions. Recent efforts have focused on identifying biomarkers associated with these changes that may be of use in predicting patients with the highest likelihood of positive clinical outcomes during allergen immunotherapy (AIT), providing guidance regarding AIT discontinuation, and predicting symptomatic relapse and the need for booster AIT after therapy. The identification of such biomarkers in food allergy has the additional benefit of replacing oral food challenges, which are presently the gold standard for diagnosing food allergies. While several markers have shown early promise, research has yet to identify a marker that can invariably predict clinical response to AIT. Skin prick testing (SPT) and specific IgE have commonly been used as inclusion criteria for the initiation of AIT and prediction of reactions during subsequent allergen challenge; however, existing data suggests that changes in these markers are not always associated with clinical improvement and can be widely variable, reducing their utility in predicting clinical response. Similar findings have been… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-20
  • A novel paraneoplastic syndrome with acquired lipodystrophy and chronic inflammatory demyelinating polyneuropathy in an adolescent male with craniopharyngioma.
    Related ArticlesA novel paraneoplastic syndrome with acquired lipodystrophy and chronic inflammatory demyelinating polyneuropathy in an adolescent male with craniopharyngioma. J Pediatr Endocrinol Metab. 2018 Feb 19;: Authors: Lockemer HE, Sumpter KM, Cope-Yokoyama S, Garg A Abstract BACKGROUND: Acquired lipodystrophy, craniopharyngioma and chronic inflammatory demyelinating polyneuropathy (CIDP) are individually rare disorders, and have never before been reported in a single patient. CASE PRESENTATION: A 15-year-7 month old Caucasian male presented with lower extremity weakness, frequent falls and abnormal fat distribution occurring over the previous 1 year. He was diagnosed with CIDP, craniopharyngioma and acquired lipodystrophy. The patient underwent tumor debulking and cranial irradiation for the craniopharyngioma, and received monthly intravenous immunoglobulin for the CIDP. The patient initially had some resolution of the lipodystrophy phenotype, but subsequently the abnormal fat distribution recurred and the patient developed additional systemic abnormalities, including mild pancytopenia and hepatic fibrosis. CONCLUSIONS: Our patient represents a novel association of acquired lipodystrophy, craniopharyngioma, and CIDP, possibly due to an as yet unidentified paraneoplastic autoantibody.PMID: 29455190 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-20
  • Investigational immunosuppressants in early stage clinical trials for the treatment of multiple sclerosis.
    Related ArticlesInvestigational immunosuppressants in early stage clinical trials for the treatment of multiple sclerosis. Expert Opin Investig Drugs. 2018 Feb 19;: Authors: Gajofatto A, Turatti M Abstract INTRODUCTION: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system with an immune mediated pathogenesis. Several therapies that suppress or modulate diverse immune system functions have been used for decades with the aim of modifying the disease course. However, these treatments have either limited efficacy or potentially serious adverse events that prevent first-line use on large scale. Areas covered. The aim of the present article is to review ongoing or recently completed clinical trials investigating immunosuppressive drugs for MS. The websites clinicaltrials.gov, clinicaltrialsregister.eu, and pubmed.gov were searched for phase 1, phase 2, and phase 3 trials starting from 2012. Twelve drugs were identified, including 7 monoclonal antibodies and 5 small molecules. Expert opinion. Current or recently completed trials of immunosuppressants for MS are mainly proof-of-concept studies enrolling patients with relapsing disease and using efficacy endpoints based on magnetic resonance imaging measures of inflammatory activity. Sphingosine 1-phosphate receptor modulators and B-cell depleting therapies represent the most commonly investigated drugs, suggesting that mechanisms of action that have already shown promise for MS treatment are being exploited to find new therapies with improved safety, tolerability, and convenience of dosing. Clinical trials of immunosuppressants for progressive MS are largely lacking.PMID: 29455558 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-20
  • Treatment of neuromyelitis optica with rituximab: a 2-year prospective multicenter study.
    Related ArticlesTreatment of neuromyelitis optica with rituximab: a 2-year prospective multicenter study. J Neurol. 2018 Feb 17;: Authors: Cabre P, Mejdoubi M, Jeannin S, Merle H, Plumelle Y, Cavillon G, Smadja D, Marignier R, Francophone Society of Multiple Sclerosis and OFSEP investigators Abstract OBJECTIVE: Neuromyelitis optica (NMO) is a very severe autoimmune disorder of the central nervous system. It affects young subjects and has a poor prognosis both on a functional and vital level. Therefore, it is imperative to reduce the frequency of relapses. The purpose of this study was to evaluate the clinical and neuroradiological effectiveness of rituximab (RTX) on active forms of NMO. METHODS: We conducted a 2-year open prospective multicenter study that included 32 patients treated with RTX at a dose of 375 mg/m2/week for 1 month. When the number of circulating CD19+ B cells reached 1%, a maintenance therapy was started, consisting of two infusions of 1 g of RTX, administered at a 15-day interval. The primary objective was to reduce the annual relapse rate (ARR), in comparison to that observed in the 2 years before treatment onset. RESULTS: Rituximab administration reduced the ARR from 1.34 to 0.56 (p = 0.0005). The average Expanded Disability Status Scale (EDSS) score significantly improved by 1.1 point, from 5.9 (2-9) to 4.8 (0-9) after 2 years (p = 0.03). Anti-aquaporin-4 antibodies' level predicted treatment failure (p = 0.03). Frequency of Gad+ lesions in spinal cord decreased from 23.3 to 14.2%. RTX treatment did not prevent the death of three patients (treatment failure in two patients and acute myeloid leukemia in… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-20
  • Differentiation of remitting neuromyelitis optica spectrum disorders from multiple sclerosis by integrating parameters from serum proteins and lymphocyte subsets.
    Related ArticlesDifferentiation of remitting neuromyelitis optica spectrum disorders from multiple sclerosis by integrating parameters from serum proteins and lymphocyte subsets. J Neuroimmunol. 2018 Feb 08;: Authors: Ip PP, Chung CY, Chang CC, Lee YF, Wang HM, Lian IB, Fann CS, Yang CC, Liao F Abstract Differential diagnosis for neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) is always doubtful. To differentiate these diseases, we studied the immune status in the blood of patients with MS (n = 45) or NMOSD (n = 23) at remission phase. Remitting NMOSD patients had increased levels of CXCL13 and memory B cells, while remitting MS patients had elevated levels of galectin-9 and Th1 cells. A diagnostic model with these four variables is built to distinguish remitting NMOSD from MS with a sensitivity of 91.30%. Our diagnostic model may help to improve the differentiation of remitting NMOSD from MS.PMID: 29455925 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-20
  • NMDAR (N-methyl-D-aspartate receptor) encephalitis in a patient with MS (multiple sclerosis): a rare and challenging case.
    Related ArticlesNMDAR (N-methyl-D-aspartate receptor) encephalitis in a patient with MS (multiple sclerosis): a rare and challenging case. BMJ Case Rep. 2018 Feb 17;2018: Authors: Suleman S, Javed Q Abstract We present a rare case of N-methyl-D-aspartate receptor (NMDAR) encephalitis in a 41-year-old Caucasian woman, who initially presented with prominent neuropsychiatric symptoms on the background of pre-existing multiple sclerosis. Here, the authors navigate the muddy water between neurology and psychiatry, describing the caveats of antibody testing with a misdiagnosed case of acute and transient psychotic episode. NMDAR encephalitis in MS is a rare condition, which can be easily confused with a new onset psychotic episode. This case report can be helpful in recognition and diagnosis of this rare condition. Making the right diagnosis is important since it can prevent an unnecessary radical treatment and long-term neuropsychiatric complications.PMID: 29455177 [PubMed - in process] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-20
  • Low Serum IgE Is a Sensitive and Specific Marker for Common Variable Immunodeficiency (CVID).
    Related ArticlesLow Serum IgE Is a Sensitive and Specific Marker for Common Variable Immunodeficiency (CVID). J Clin Immunol. 2018 Feb 17;: Authors: Lawrence MG, Palacios-Kibler TV, Workman LJ, Schuyler AJ, Steinke JW, Payne SC, McGowan EC, Patrie J, Fuleihan RL, Sullivan KE, Lugar PL, Hernandez CL, Beakes DE, Verbsky JW, Platts-Mills TAE, Cunningham-Rundles C, Routes JM, Borish L Abstract Although small prior studies have suggested that IgE can be low in common variable immunodeficiency (CVID), the workup for patients with recurrent infections and suspected hypogammaglobulinemia does not include the routine measurement of serum IgE. We sought to test the hypothesis that low/undetectable serum IgE is characteristic of CVID by comparing the frequency of low/undetectable serum IgE in healthy controls and patients with CVID. We measured total serum IgE in a large multi-center cohort of patients with CVID (n = 354) and compared this to large population-based cohorts of children and adults. We further compared IgE levels in patients with CVID to those with other forms of humoral immunodeficiency, and in a subset, measured levels of allergen-specific serum IgE and IgG subclasses. Lastly, we evaluated for the presence of IgE in commercially available immunoglobulin replacement therapy (IgRT) products. An undetectable serum IgE (< 2 IU/ml) occurs in only 3.3% (95% CI, 1.9-5.7%) of the general population. In contrast, an undetectable IgE occurs in 75.6% (95% CI, 65.6-85.7%) of patients with CVID. Conversely, a high IgE (> 180 IU/ml) is very uncommon in CVID (0.3% of patients). IgE is > 2 IU/ml in 91.2% of patients with secondary hypogammaglobulinemia, and… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-18
  • Humoral response to John Cunningham virus during pregnancy in multiple sclerosis.
    Related ArticlesHumoral response to John Cunningham virus during pregnancy in multiple sclerosis. Mult Scler Relat Disord. 2018 Feb 09;21:11-18 Authors: Saraste M, Atula S, Hedman K, Hurme S, Jalkanen A, Sneck M, Surcel HM, Maghzi AH, Airas L Abstract BACKGROUND: Pregnancy induces an immunosuppressive state in the mother to ensure immunological acceptance of the foetus. Impairment of cell-mediated immune responses may render the mother susceptible to intracellular pathogens. It is not presently known whether pregnancy alters the immunosurveillance for John Cunningham virus (JCV), an opportunistic pathogen associated with natalizumab treatment for multiple sclerosis (MS). OBJECTIVE: To evaluate whether the humoral immune response to JCV is altered during pregnancy among MS patients and healthy controls to get insight to potential pregnancy-induced alterations related to immune response to JCV during pregnancy. METHODS: Serum anti-JCV-antibody-indices (JCV-Ab-index) were determined by a two-step second-generation enzyme-linked immunosorbent assay in 49 MS patients during and after pregnancy and in 49 healthy controls during pregnancy. For comparison, total IgG levels and antibodies against Epstein-Barr, cytomegalo and measles viruses were similarly measured. RESULTS: The JCV-Ab-indices of MS patients were not altered during the pregnancy (1st vs. 3rd trimester, 0.62 vs. 0.77, p = 0.99). Contrary to this, in the healthy controls JCV-Ab-indices (p = 0.005), antibody levels to the other viruses, and total IgG levels (p < 0.0001) decreased significantly during pregnancy. CONCLUSIONS: JCV-Ab levels remain unaltered during MS pregnancy, while the total IgG concentration is reduced/diluted due to increasing plasma volumes during the course of pregnancy. This may… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-18
  • Amelioration of progressive autoimmune encephalomyelitis by epigenetic regulation involves selective repression of mature neutrophils during the preclinical phase.
    Related ArticlesAmelioration of progressive autoimmune encephalomyelitis by epigenetic regulation involves selective repression of mature neutrophils during the preclinical phase. Exp Neurol. 2018 Feb 14;: Authors: Jayaraman A, Sharma M, Prabhakar B, Holterman M, Jayaraman S Abstract We have recently demonstrated that treatment of NOD mice with the epigenetic drug Trichostatin A (TSA) ameliorated myelin peptide induced progressive experimental autoimmune encephalomyelitis (P-EAE). Protection was accompanied by induction of antigen-specific T-cell tolerance in the periphery and reduced the influx of T cells into the spinal cord. In this investigation, we examined whether the epigenetic drug could impact the innate immune system as well. Whereas the mature (MHC class II+) CD11b+Ly-6G+ neutrophils expanded substantially in the peripheral lymphoid compartment during the preclinical phase, the MHC class II+, CD11b+Ly-6C+ mature monocytes increased modestly throughout the disease course. Amelioration of the clinical disease by TSA treatment was accompanied by diminished abundance of CD11b+Ly-6Gdim activated neutrophils in secondary lymphoid organs and their influx into the spinal cord without affecting monocytes. Interestingly, the co-inhibitory ligand CD274+ (PD-L1+) but not CD275+ (ICOS-L+), CD39+ or CD11c+ dendritic cells were decreased in the peripheral lymphoid compartment of drug treated mice. Thus, in addition to myelin-specific T cell tolerance induction observed previously, selective repression of mature neutrophils and PD-L1+ cells is critically involved in the epigenetic regulation of P-EAE.PMID: 29453977 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-18
  • Treatment and outcomes in patients with IgG4-related disease using the IgG4 responder index.
    Treatment and outcomes in patients with IgG4-related disease using the IgG4 responder index. Joint Bone Spine. 2018 Feb 13;: Authors: Fernández-Codina A, Pinilla B, Pinal-Fernández I, López C, Fraile-Rodríguez G, Fonseca-Aizpuru E, Carballo I, Brito-Zerón P, Feijóo-Massó C, López-Dupla M, Cid MC, Martínez-Valle F, Spanish Registry of IgG4 Related Disease (REERIGG4) investigators, Autoimmune Diseases Group (GEAS), Spanish Internal Medicine Society (SEMI) Abstract BACKGROUND: IgG4-related disease (IgG4-RD) is an autoimmune disease triggering an inflammatory cascade that leads to fibrosis. Outcome measures are limited and treatment options remain underexplored. OBJECTIVES: To assess the variation of the IgG4 responder index (IgG4-RI) in a cohort of IgG4-RD patients and to explore their treatments and outcomes. METHODS: We studied the clinical phenotype, severity of the disease and response to treatment in an ambispective multicenter cohort study including 14 different hospitals in Spain. All patients met the 2012 international consensus on pathology criteria for diagnosis. RESULTS: Sixty-eight patients were included, with a mean age of 53.4 years and predominance of male sex. The most commonly involved tissues were: retroperitoneum (33%), orbital pseudotumor (28%), and maxillary and paranasal sinuses (24%). IgG4-RI values were higher in patients with multiorgan disease and before treatment. After being treated, IgG4-RI values were lower, in accordance with the high rates of treatment response. Most patients received: glucocorticoids (GC), surgery, azathioprine (AZA), mofetil mycophenolate (MMF) or rituximab. GC alone, GC plus surgery and GC plus AZA were given in the most of the IgG4 disease activity episodes. All treatments had high response rates… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-17
  • Radiologically isolated syndrome or subclinical multiple sclerosis: MAGNIMS consensus recommendations.
    Related ArticlesRadiologically isolated syndrome or subclinical multiple sclerosis: MAGNIMS consensus recommendations. Mult Scler. 2018 Feb;24(2):214-221 Authors: De Stefano N, Giorgio A, Tintoré M, Pia Amato M, Kappos L, Palace J, Yousry T, Rocca MA, Ciccarelli O, Enzinger C, Frederiksen J, Filippi M, Vrenken H, Rovira À, MAGNIMS study group PMID: 29451440 [PubMed - in process] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-17
  • Corrigendum to “Argentinean recommendations on the identification of treatment failure in relapsing remitting multiple sclerosis patients” [J. Neurol. Sci. 385C (2018) 217-224].
    Related ArticlesCorrigendum to "Argentinean recommendations on the identification of treatment failure in relapsing remitting multiple sclerosis patients" [J. Neurol. Sci. 385C (2018) 217-224]. J Neurol Sci. 2018 Feb 12;: Authors: Cristiano E, Alonso R, Alvez Pinheiro A, Bacile EA, Balbuena ME, Ballario C, Barboza AG, Bestoso S, Burgos M, Cáceres F, Carnero Contentti E, Carrá A, Crespo E, Curbelo MC, Deri N, Fernandez J, Fernández Liguori N, Fiol M, Gaitán MI, Garcea O, Giunta D, Halfon MJ, Hryb JP, Jacobo M, Kohler E, Linares R, Luetic GG, Martínez AD, Míguez J, Nofal PG, Patrucco L, Piedrabuena R, Rojas JI, Rotta Escalante R, Saladino ML, Silva BA, Sinay V, Steinberg JD, Tarulla A, Vétere SA, Villa A, Vrech C, Ysrraelit MC, Correale J PMID: 29449007 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-17
  • Neurofilament light chain and oligoclonal bands are prognostic biomarkers in radiologically isolated syndrome.
    Neurofilament light chain and oligoclonal bands are prognostic biomarkers in radiologically isolated syndrome. Brain. 2018 Feb 14;: Authors: Matute-Blanch C, Villar LM, Álvarez-Cermeño JC, Rejdak K, Evdoshenko E, Makshakov G, Nazarov V, Lapin S, Midaglia L, Vidal-Jordana A, Drulovic J, García-Merino A, Sánchez-López AJ, Havrdova E, Saiz A, Llufriu S, Alvarez-Lafuente R, Schroeder I, Zettl UK, Galimberti D, Ramió-Torrentà L, Robles R, Quintana E, Hegen H, Deisenhammer F, Río J, Tintoré M, Sánchez A, Montalban X, Comabella M Abstract The prognostic role of cerebrospinal fluid molecular biomarkers determined in early pathogenic stages of multiple sclerosis has yet to be defined. In the present study, we aimed to investigate the prognostic value of chitinase 3 like 1 (CHI3L1), neurofilament light chain, and oligoclonal bands for conversion to clinically isolated syndrome and to multiple sclerosis in 75 patients with radiologically isolated syndrome. Cerebrospinal fluid levels of CHI3L1 and neurofilament light chain were measured by enzyme-linked immunosorbent assay. Uni- and multivariable Cox regression models including as covariates age at diagnosis of radiologically isolated syndrome, number of brain lesions, sex and treatment were used to investigate associations between cerebrospinal fluid CHI3L1 and neurofilament light chain levels and time to conversion to clinically isolated syndrome and multiple sclerosis. Neurofilament light chain levels and oligoclonal bands were independent risk factors for the development of clinically isolated syndrome (hazard ratio = 1.02, P = 0.019, and hazard ratio = 14.7, P = 0.012, respectively) and multiple sclerosis (hazard ratio = 1.03, P = 0.003, and hazard ratio… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2018-02-17