LECTURAS CIENTÍFICAS

  • Effect of Grass Sublingual Tablet Immunotherapy is Similar in Children and Adults: A Bayesian Approach To Design Pediatric Sublingual Immunotherapy Trials.
    Related ArticlesEffect of Grass Sublingual Tablet Immunotherapy is Similar in Children and Adults: A Bayesian Approach To Design Pediatric Sublingual Immunotherapy Trials. J Allergy Clin Immunol. 2017 Dec 05;: Authors: Kaur A, Skoner D, Ibrahim J, Li Q, Lockey RF, Blaiss M, Bufe A, Andersen JS, Canonica GW, Nolte H Abstract BACKGROUND: Large sample sizes are needed for sublingual immunotherapy (SLIT) trials due to inherent data variability secondary to inconsistent allergen exposure. Obtaining large sample sizes for pediatric SLIT trials is challenging, but a Bayesian approach using prior adult data can reduce the necessary sample size. OBJECTIVE: To describe how a Bayesian framework utilizing prior information from adult trials can be used to improve pediatric SLIT clinical development. METHODS: Data were compiled using a frequentist approach (conventional clinical trial approach independent of prior data) from trials conducted during the clinical development of timothy grass SLIT-tablet. RESULTS: The treatment effect of timothy grass SLIT-tablet was considered similar between pediatric (N=795) and adult (N=2299) data pools, with relative total combined symptom plus medication score improvement (95% CI) vs placebo of 21% (11.0, 30.4) and 20% (14.6, 24.4), respectively. Phleum pratense-specific IgG4 and IgE blocking factor increased from baseline in both children and adults treated with timothy grass SLIT-tablet. Given the reasonable assumption in similarity of treatment response between adults and children, a Bayesian approach is described to demonstrate rigorous efficacy criterion for pediatric trials incorporating information from prior adult trials, and thereby reduce the sample size. CONCLUSIONS: Data support the similarity of… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-10
  • Mechanisms of allergen immunotherapy for inhaled allergens and predictive biomarkers.
    Related ArticlesMechanisms of allergen immunotherapy for inhaled allergens and predictive biomarkers. J Allergy Clin Immunol. 2017 Dec;140(6):1485-1498 Authors: Shamji MH, Durham SR Abstract Allergen immunotherapy is effective in patients with IgE-dependent allergic rhinitis and asthma. When immunotherapy is given continuously for 3 years, there is persistent clinical benefit for several years after its discontinuation. This disease-modifying effect is both antigen-specific and antigen-driven. Clinical improvement is accompanied by decreases in numbers of effector cells in target organs, including mast cells, basophils, eosinophils, and type 2 innate lymphoid cells. Immunotherapy results in the production of blocking IgG/IgG4 antibodies that can inhibit IgE-dependent activation mediated through both high-affinity IgE receptors (FcεRI) on mast cells and basophils and low-affinity IgE receptors (FcεRII) on B cells. Suppression of TH2 immunity can occur as a consequence of either deletion or anergy of antigen-specific T cells; induction of antigen-specific regulatory T cells; or immune deviation in favor of TH1 responses. It is not clear whether the altered long-term memory resides within the T-cell or the B-cell compartment. Recent data highlight the role of IL-10-producing regulatory B cells and "protective" antibodies that likely contribute to long-term tolerance. Understanding mechanisms underlying induction and persistence of tolerance should identify predictive biomarkers of clinical response and discover novel and more effective strategies for immunotherapy.PMID: 29221580 [PubMed - in process] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-10
  • Gastrointestinal manifestation of immunoglobulin G4-related disease: clarification through a multicenter survey.
    Related ArticlesGastrointestinal manifestation of immunoglobulin G4-related disease: clarification through a multicenter survey. J Gastroenterol. 2017 Dec 08;: Authors: Notohara K, Kamisawa T, Uchida K, Zen Y, Kawano M, Kasashima S, Sato Y, Shiokawa M, Uehara T, Yoshifuji H, Hayashi H, Inoue K, Iwasaki K, Kawano H, Matsubayashi H, Moritani Y, Murakawa K, Oka Y, Tateno M, Okazaki K, Chiba T Abstract BACKGROUND: Several reports on immunoglobulin (Ig)G4-related disease (IgG4-RD) with gastrointestinal involvement (IgG4-related gastrointestinal disease; IgG4-GID) have been published, although this entity has not been fully established clinicopathologically. Thus, we carried out a multicenter survey. METHODS: Patients with possible IgG4-GID who underwent resection were collected. Histologic slides were reevaluated, and eight cases with diffuse lymphoplasmacytic infiltration but without numerous neutrophils, granulations or epithelioid granulomas were further analyzed. RESULTS: Overall, the IgG4 counts (87-345/high-power field) and IgG4/IgG-positive ratio were high (44-115%). The demographic findings included advanced age among the patients (55-80 years) and male preponderance (six cases). Six lesions (five gastric, one esophageal), consisting of lymphoplasmacytic infiltration with neural involvement in the muscularis propria and/or bottom-heavy plasmacytosis in the gastric mucosa, were histologically regarded as highly suggestive of IgG4-RD. Storiform fibrosis and obliterative phlebitis were found in two cases, and the former gave rise to a 7-cm-sized inflammatory pseudotumor (IPT) in one case. Ulceration and carcinoma co-existed in three and two lesions, respectively. All the patients had other organ involvement (OOI), and serum IgG4 levels were markedly elevated (four of five patients). The remaining two cases with gastric IPTs featuring reactive nodular… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-10
  • Immune stealth-driven O2 serotype prevalence and potential for therapeutic antibodies against multidrug resistant Klebsiella pneumoniae.
    Related ArticlesImmune stealth-driven O2 serotype prevalence and potential for therapeutic antibodies against multidrug resistant Klebsiella pneumoniae. Nat Commun. 2017 Dec 08;8(1):1991 Authors: Pennini ME, De Marco A, Pelletier M, Bonnell J, Cvitkovic R, Beltramello M, Cameroni E, Bianchi S, Zatta F, Zhao W, Xiao X, Camara MM, DiGiandomenico A, Semenova E, Lanzavecchia A, Warrener P, Suzich J, Wang Q, Corti D, Stover CK Abstract Emerging multidrug-resistant bacteria are a challenge for modern medicine, but how these pathogens are so successful is not fully understood. Robust antibacterial vaccines have prevented and reduced resistance suggesting a pivotal role for immunity in deterring antibiotic resistance. Here, we show the increased prevalence of Klebsiella pneumoniae lipopolysaccharide O2 serotype strains in all major drug resistance groups correlating with a paucity of anti-O2 antibodies in human B cell repertoires. We identify human monoclonal antibodies to O-antigens that are highly protective in mouse models of infection, even against heavily encapsulated strains. These antibodies, including a rare anti-O2 specific antibody, synergistically protect against drug-resistant strains in adjunctive therapy with meropenem, a standard-of-care antibiotic, confirming the importance of immune assistance in antibiotic therapy. These findings support an antibody-based immunotherapeutic strategy even for highly resistant K. pneumoniae infections, and underscore the effect humoral immunity has on evolving drug resistance.PMID: 29222409 [PubMed - in process] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-10
  • Investigation of markers of allergic sensitization and viral infections in children with allergy and asthma.
    Related ArticlesInvestigation of markers of allergic sensitization and viral infections in children with allergy and asthma. Acta Med Litu. 2017;24(3):145-152 Authors: Dubakienė R, Rubinaitė V, Petronytė M, Dalgėdienė I, Rudzevičienė O, Dubakaitė D, Rudalevičienė P, Žvirblienė A Abstract Background: Allergic diseases are the most prevalent chronic diseases in the developed countries. It is believed that early allergic sensitization and respiratory viral infections play an important role in the development of allergic diseases and asthma. Methods: The current study investigated the correlation between asthma, allergy, and various markers - allergen-specific IgE, IgG4 and IgA, ECP, IgM, and IgG antibodies against respiratory viruses hRSV and hPIV1-4 - in blood serum samples from 80 children (mean age 5.2 years) recruited from the Lithuanian birth cohort. Children were divided into three groups according to their diagnosis: asthma (n = 25), allergy without asthma (n = 14), and control group (n = 41). Results: Based on retrospective data, airway infections and bronchitis by the age of two years were associated with asthma in later childhood. The presence of IgM and IgG antibodies against hRSV and hPIV1-4 at the age of five years were not associated with asthma and allergy: a high rate of persistent or past respiratory viral infections was revealed in all three groups. Among allergic children, increased levels of allergen-specific IgE and d1-specific IgG4 were determined. Conclusion: The current study provides new insights into the relationships between allergic sensitization and respiratory virus infections in children.PMID: 29217968 [PubMed] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-09
  • IgG4-related disease presenting as hoarseness and postcricoid ulcer.
    Related ArticlesIgG4-related disease presenting as hoarseness and postcricoid ulcer. Ann Allergy Asthma Immunol. 2017 Dec 04;: Authors: Hamadani S, Wang B, Gupta S PMID: 29217085 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-09
  • Idiopathic retroperitoneal fibrosis: a cross-sectional study of 142 Chinese patients.
    Idiopathic retroperitoneal fibrosis: a cross-sectional study of 142 Chinese patients. Scand J Rheumatol. 2017 Dec 08;:1-8 Authors: Liao S, Wang Y, Li K, Zhu J, Zhang J, Huang F Abstract OBJECTIVE: To investigate the epidemiological, clinicolaboratory, imaging, and therapeutic characteristics of idiopathic retroperitoneal fibrosis (iRPF) in China. METHOD: All patients presenting to the Chinese People's Liberation Army General Hospital from October 1996 to July 2016 diagnosed with iRPF were included. Data were collected from medical records and the smoking index was calculated. Scheel radiological classification was used to assess the extent of soft-tissue density. RESULTS: The study included 142 patients (120 men, 22 women). The mean age was 54.3 years. Disease duration ranged from 0.23 to 109.5 months (median 2.7). Current smoking rate was 53.5%. Flank pain was more common in males (p = 0.041) and in the high smoking index group (p = 0.03). C-reactive protein level ranged from 0.08 to 8.9 mg/dL (median 1.9). Serum immunoglobulin G4 (IgG4) was elevated in 31/63 patients (49.2%), and males had higher IgG4 concentrations (p = 0.017) at presentation. Respectively, 44.4%, 5.6%, and 22.5% of cases were classified into Scheel classes I, II, and III. Eight patients (5.6%) had atypical RPF localization and 103 (72.5%) presented with hydronephrosis, which was more common in class III patients (p = 0.04). Nine patients (6.3%) received no treatment; the others received medical (34.5%) or surgical treatment (14.8%), or both (44.4%). CONCLUSIONS: There was a higher rate in males and younger age at disease onset in these Chinese iRPF patients than in other populations. Acute-phase reactants and… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-09
  • The protein tyrosine phosphatase Shp2 regulates oligodendrocyte differentiation and early myelination and contributes to timely remyelination.
    Related ArticlesThe protein tyrosine phosphatase Shp2 regulates oligodendrocyte differentiation and early myelination and contributes to timely remyelination. J Neurosci. 2017 Dec 07;: Authors: Ahrendsen JT, Harlow DE, Finseth LT, Bourne JN, Hickey SP, Gould EA, Culp CM, Macklin WB Abstract Shp2 is a nonreceptor protein tyrosine phosphatase that has been shown to influence neurogenesis, oligodendrogenesis, and oligodendrocyte differentiation. Furthermore, Shp2 is a known regulator of the Akt/mTOR and ERK signaling pathways in multiple cellular contexts, including oligodendrocytes. Its role during later postnatal CNS development or in response to demyelination injury has not been examined. Based on the current studies, we hypothesize that Shp2 is a negative regulator of CNS myelination. Using transgenic mouse technology, we show that Shp2 is involved in oligodendrocyte differentiation and early myelination, but is not necessary for myelin maintenance. We also show that Shp2 regulates the timely differentiation of oligodendrocytes following lysolecithin-induced demyelination, although apparently normal remyelination occurs at a delayed time point. These data suggest that Shp2 is a relevant therapeutic target in demyelinating diseases such as multiple sclerosis.SIGNIFICANCE STATEMENTIn the present study, we show that the protein phosphatase Shp2 is an important mediator of oligodendrocyte differentiation and myelination, both during developmental myelination as well as in myelin regeneration. We provide important insight into the signaling mechanisms regulating myelination and propose that Shp2 acts as a transient brake to the developmental myelination process. Furthermore, we show that Shp2 regulates oligodendrocyte differentiation following demyelination and therefore has important therapeutic implications in diseases such as multiple sclerosis.PMID:… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-09
  • Clinical Reasoning: Left hemiparesis, ataxia, and optic neuritis in a child previously treated for pineoblastoma.
    Related ArticlesClinical Reasoning: Left hemiparesis, ataxia, and optic neuritis in a child previously treated for pineoblastoma. Neurology. 2016 04 12;86(15):e161-5 Authors: Vila-Bedmar S, Nourbakhsh B, Anzalone S, Waubant E PMID: 27163667 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-09
  • Corrigendum: Development and function of human innate immune cells in a humanized mouse model.
    Corrigendum: Development and function of human innate immune cells in a humanized mouse model. Nat Biotechnol. 2017 Dec 08;35(12):1211 Authors: Rongvaux A, Willinger T, Martinek J, Strowig T, Gearty SV, Teichmann LL, Saito Y, Marches F, Halene S, Palucka AK, Manz MG, Flavell RA PMID: 29220023 [PubMed - in process] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-09
  • PML in a person with multiple sclerosis: Is teriflunomide the felon?
    PML in a person with multiple sclerosis: Is teriflunomide the felon? Neurology. 2017 Dec 06;: Authors: Lorefice L, Fenu G, Gerevini S, Frau J, Coghe G, Barracciu MA, Contu F, Marrosu MG, Cocco E PMID: 29212829 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-08
  • Diet quality is associated with disability and symptom severity in multiple sclerosis.
    Diet quality is associated with disability and symptom severity in multiple sclerosis. Neurology. 2017 Dec 06;: Authors: Fitzgerald KC, Tyry T, Salter A, Cofield SS, Cutter G, Fox R, Marrie RA Abstract OBJECTIVE: To assess the association between diet quality and intake of specific foods with disability and symptom severity in people with multiple sclerosis (MS). METHODS: In 2015, participants in the North American Research Committee on MS (NARCOMS) Registry completed a dietary screener questionnaire that estimates intake of fruits, vegetables and legumes, whole grains, added sugars, and red/processed meats. We constructed an overall diet quality score for each individual based on these food groups; higher scores denoted a healthier diet. We assessed the association between diet quality and disability status as measured using Patient-Determined Disease Steps (PDDS) and symptom severity using proportional odds models, adjusting for age, sex, income, body mass index, smoking status, and disease duration. We assessed whether a composite healthy lifestyle measure, a healthier diet, healthy weight (body mass index <25), routine physical activity, and abstinence from smoking was associated with symptom severity. RESULTS: Of the 7,639 (68%) responders, 6,989 reported physician-diagnosed MS and provided dietary information. Participants with diet quality scores in the highest quintile had lower levels of disability (PDDS; proportional odds ratio [OR] for Q5 vs Q1 0.80; 95% confidence interval [CI] 0.69-0.93) and lower depression scores (proportional OR for Q5 vs Q1 0.82; 95% CI 0.70-0.97). Individuals reporting a composite healthy lifestyle had lower odds of reporting severe fatigue (0.69; 95% CI… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-08
  • Diet in multiple sclerosis: Science takes a seat at the table.
    Diet in multiple sclerosis: Science takes a seat at the table. Neurology. 2017 Dec 06;: Authors: Sumowski JF, McDonnell GV, Bourdette D PMID: 29212826 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-08
  • Multicenter evaluation of neurofilaments in early symptom onset amyotrophic lateral sclerosis.
    Multicenter evaluation of neurofilaments in early symptom onset amyotrophic lateral sclerosis. Neurology. 2017 Dec 06;: Authors: Feneberg E, Oeckl P, Steinacker P, Verde F, Barro C, Van Damme P, Gray E, Grosskreutz J, Jardel C, Kuhle J, Koerner S, Lamari F, Amador MDM, Mayer B, Morelli C, Muckova P, Petri S, Poesen K, Raaphorst J, Salachas F, Silani V, Stubendorff B, Turner MR, Verbeek MM, Weishaupt JH, Weydt P, Ludolph AC, Otto M Abstract OBJECTIVE: To examine neurofilament (Nf) concentrations according to symptom onset and clinical diagnostic certainty categories of amyotrophic lateral sclerosis (ALS). METHODS: We measured Nf light chain (NfL) and phosphorylated Nf heavy chain (pNfH) CSF and NfL serum levels in patients with ALS with first symptom onset ≤6 months (n = 54) or >6 months (n = 135) from sampling, and patients with other neurologic diseases, differential diagnoses of a motor neuron disease (MND mimics), and other MND variants to determine the diagnostic accuracy in patients with ALS with early symptom onset. Samples were received multicentric and analyzed by ELISA and Simoa platform and related to other clinical measures. RESULTS: NfL and pNfH in CSF and NfL in serum were increased in early and later symptomatic phase ALS (p < 0.0001). CSF and serum NfL and CSF pNfH discriminated patients with ALS with early symptom onset from those with other neurologic diseases and MND mimics with high sensitivity (94%, 88%, 98%, and 89%, 100%, 78%) and specificity (86%, 92%, 91%, and 94%, 90%, 98%) and did not… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-08
  • Acquired haemophilia A complicating alemtuzumab therapy for multiple sclerosis.
    Acquired haemophilia A complicating alemtuzumab therapy for multiple sclerosis. BMJ Case Rep. 2017 Dec 05;2017: Authors: McCaughan G, Massey J, Sutton I, Curnow J Abstract Alemtuzumab is a highly efficacious therapy used in the treatment of multiple sclerosis (MS), but uncoupling of T and B cell repopulation during immune reconstitution associates with an increasing range of secondary B cell-mediated autoimmune complications. A 34-year-old woman developed Graves' disease 11 months following an initial course of alemtuzumab treatment for MS. Nine months following the second treatment with alemtuzumab, the patient presented with spontaneous intramuscular and subcutaneous haemorrhage due to development of an inhibitory autoantibody to coagulation factor VIII. Acquired haemophilia A (AHA) is an extremely rare complication in patients treated with alemtuzumab. Treatment with rituximab may induce a rapid remission of AHA; however, the patient's high John Cunningham virus (JCV) antibody index and alemtuzumab-induced T cell lymphopenia may lead to an increased risk of progressive multifocal leucoencephalopathy, a potential complication which was unacceptable to the patient.PMID: 29212866 [PubMed - in process] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-08
  • Do patients with schizophreniform and bipolar disorders show an intrathecal, polyspecific, antiviral immune response? A pilot study.
    Do patients with schizophreniform and bipolar disorders show an intrathecal, polyspecific, antiviral immune response? A pilot study. Fluids Barriers CNS. 2017 Dec 07;14(1):34 Authors: Endres D, Huzly D, Dersch R, Stich O, Berger B, Schuchardt F, Perlov E, Venhoff N, Hellwig S, Fiebich BL, Erny D, Hottenrott T, Tebartz van Elst L Abstract BACKGROUND: We previously described inflammatory cerebrospinal fluid (CSF) alterations in a subgroup of patients with schizophreniform disorders and the synthesis of polyspecific intrathecal antibodies against different neurotropic infectious pathogens in some patients with bipolar disorders. Consequently, we have measured the prevalence of a positive MRZ reaction (MRZR)-a marker for a polyspecific, antiviral, intrathecal, humoral immune response composed of three antibody indices for the neurotropic viruses of measles (M), rubella (R), and varicella zoster (Z)-in these patients. METHODS: We analyzed paired CSF and serum samples of 39 schizophreniform and 39 bipolar patients. For comparison, we used a group of 48 patients with other inflammatory neurological disorders (OIND) and a cohort of 203 multiple sclerosis (MS) patients. RESULTS: We found a positive MRZR in two patients with schizophreniform disorders (5.1%); both suffered from schizodepressive disorders without any other signs suggestive of MS. None of the bipolar patients (0%) and four members of the OIND group (8.3%) showed a positive MRZR. In the MS cohort, a positive MRZR was found significantly more frequently [in 99 patients (48.8%)] than in the other patient groups (p > 0.001). In summary, we did not find a positive MRZR in a relevant subgroup of patients with… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-08
  • ICAM1+ neutrophils promote chronic inflammation via ASPRV1 in B cell-dependent autoimmune encephalomyelitis.
    ICAM1+ neutrophils promote chronic inflammation via ASPRV1 in B cell-dependent autoimmune encephalomyelitis. JCI Insight. 2017 Dec 07;2(23): Authors: Hawkins RFW, Patenaude A, Dumas A, Jain R, Tesfagiorgis Y, Kerfoot S, Matsui T, Gunzer M, Poubelle PE, Larochelle C, Pelletier M, Vallières L Abstract Neutrophils contribute to demyelinating autoimmune diseases, yet their phenotype and functions have been elusive to date. Here, we demonstrate that ICAM1 surface expression distinguishes extra- from intravascular neutrophils in the mouse CNS during experimental autoimmune encephalomyelitis (EAE). Transcriptomic analysis of these 2 subpopulations indicated that neutrophils, once extravasated, acquire macrophage-like properties, including the potential for immunostimulation and MHC class II-mediated antigen presentation. In corroboration, super-resolution (3D stimulated emission-depletion [STED]) microscopy revealed neutrophils forming synapses with T and B cells in situ. Further, neutrophils specifically express the aspartic retroviral-like protease ASPRV1, which increases in the CNS during EAE and severe cases of multiple sclerosis. Without ASPRV1, mice immunized with a new B cell-dependent myelin antigen (but not with the traditional myelin oligodendrocyte glycoprotein peptide) develop a chronic phase of EAE that is less severe and even completely fades in many individuals. Therefore, ICAM1+ macrophage-like neutrophils can play both shared and nonredundant roles in autoimmune demyelination, among them perpetuating inflammation via ASPRV1.PMID: 29212956 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-08
  • The electrophysiological response to immunoglobulin therapy in chronic inflammatory demyelinating polyneuropathy.
    Related ArticlesThe electrophysiological response to immunoglobulin therapy in chronic inflammatory demyelinating polyneuropathy. Acta Neurol Scand. 2017 Jun;135(6):656-662 Authors: Otto M, Markvardsen L, Tankisi H, Jakobsen J, Fuglsang-Frederiksen A Abstract OBJECTIVE: To characterize changes in motor nerve conduction studies (MNCS) and motor unit number index (MUNIX) following treatment with subcutaneous immunoglobulin and to assess whether these changes are related to muscle strength. METHODS: Data from 23 patients participating in a randomized, controlled trial were analyzed. MNCS and MUNIX were performed before and after 12 weeks of treatment. Isokinetic strength (IMS) was measured in various muscles together with grip strength (GS). RESULTS: Proximally evoked compound muscle action potential (CMAP) amplitudes and MUNIX tended to be better preserved in treated patients (P=.049 and .045). Changes in other parameters did not differ between groups. There was no correlation between changes in electrophysiological parameters and IMS. Changes in GS were related to median nerve motor conduction velocity, distal motor latency, CMAP amplitudes, and distally evoked CMAP duration (P=.013-.035). CONCLUSION: Proximally evoked CMAP amplitudes appear to be the best MNCS parameter to assess treatment outcome in chronic inflammatory demyelinating polyneuropathy.PMID: 27546708 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-08
  • Evidence of the efficacy and safety of house dust mite subcutaneous immunotherapy in elderly allergic rhinitis patients: a randomized, double-blind placebo-controlled trial.
    Evidence of the efficacy and safety of house dust mite subcutaneous immunotherapy in elderly allergic rhinitis patients: a randomized, double-blind placebo-controlled trial. Clin Transl Allergy. 2017;7:43 Authors: Bożek A, Kołodziejczyk K, Kozłowska R, Canonica GW Abstract Background: Allergen specific immunotherapy (AIT) in elderly patients is controversial, and there is still little evidence supporting the safety and efficacy of this treatment in this population. The study objective was to evaluate the safety and efficacy of AIT for house dust mite allergens in patients over 65 years of age with allergic rhinitis (AR) and a documented allergy to house dust mites. The primary endpoint was the change from baseline in the mean average adjusted symptom score (AAdSS) and the total combined rhinitis score (TCRS) difference in the least square means for the label compared to placebo. Methods: Fifty-eight AR elderly patients who were monosensitized to house dust mites were individually randomized in comparable numbers to one of two parallel groups with the following interventions: 2 years of perennial AIT using PURETHAL Mites or placebo. The symptoms and medication scores were presented as the AAdSS and TCRS. Quality of life, based on the rhinoconjunctivitis quality of life questionnaire (RQLQ), nasal allergen provocation responsiveness, serum allergen-specific IgG4 to D. pteronyssinus and D. farinae and Der p1 and Der p2 were monitored. The intent-to-treat population was analysed. Results: After 24 months of AIT, AAdSS significantly decreased from 4.27 ± 1.58 to 1.82 ± 0.71 (p < 0.05). The TCRS was significantly decreased after 2 years of AIT. Serum-specific IgG4 against D. pteronyssinus, D. farinae, Der… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-08
  • [Autoimmune pancreatitis and IgG4-related hepatic inflammatory pseudotumor complicated by an impacted pancreatic stone at the major papilla during steroid treatment].
    [Autoimmune pancreatitis and IgG4-related hepatic inflammatory pseudotumor complicated by an impacted pancreatic stone at the major papilla during steroid treatment]. Nihon Shokakibyo Gakkai Zasshi. 2017;114(12):2158-2166 Authors: Kataoka K, Achiwa K Abstract A 79-year-old male presented to our hospital with abdominal discomfort and was diagnosed with mass-forming pancreatitis. During follow-up, pancreatic stones and a hepatic mass with peripheral bile duct dilation were discovered. Serum IgG4 level was elevated, and a liver tumor biopsy revealed numerous IgG4-positive plasma cells and fibrosis. Chronic pancreatitis with the suspected involvement of autoimmune pancreatitis (AIP) and IgG4-related hepatic inflammatory pseudotumor (IgG4-HIP) was diagnosed. Therefore, a steroid treatment was initiated. However, 2 months later, the patient complained of epigastric pain that was found to be caused by an impacted pancreatic stone in the major papilla, which was endoscopically removed. Follow-up imaging findings confirmed the improvement in AIP and the dissolution of the IgG4-HIP.PMID: 29213027 [PubMed - in process] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-08
  • PD-L1 Prevents the Development of Autoimmune Heart Disease in Graft-versus-Host Disease.
    PD-L1 Prevents the Development of Autoimmune Heart Disease in Graft-versus-Host Disease. J Immunol. 2017 Dec 06;: Authors: Juchem KW, Sacirbegovic F, Zhang C, Sharpe AH, Russell K, McNiff JM, Demetris AJ, Shlomchik MJ, Shlomchik WD Abstract Effector memory T cells (TEM) are less capable of inducing graft-versus-host disease (GVHD) compared with naive T cells (TN). Previously, in the TS1 TCR transgenic model of GVHD, wherein TS1 CD4 cells specific for a model minor histocompatibility Ag (miHA) induce GVHD in miHA-positive recipients, we found that cell-intrinsic properties of TS1 TEM reduced their GVHD potency relative to TS1 TN Posttransplant, TS1 TEM progeny expressed higher levels of PD-1 than did TS1 TN progeny, leading us to test the hypothesis that TEM induce less GVHD because of increased sensitivity to PD-ligands. In this study, we tested this hypothesis and found that indeed TS1 TEM induced more severe skin and liver GVHD in the absence of PD-ligands. However, lack of PD-ligands did not result in early weight loss and colon GVHD comparable to that induced by TS1 TN, indicating that additional pathways restrain alloreactive TEM TS1 TN also caused more severe GVHD without PD-ligands. The absence of PD-ligands on donor bone marrow was sufficient to augment GVHD caused by either TEM or TN, indicating that donor PD-ligand-expressing APCs critically regulate GVHD. In the absence of PD-ligands, both TS1 TEM and TN induced late-onset myocarditis. Surprisingly, this was an autoimmune manifestation, because its development required non-TS1 polyclonal CD8+ T cells. Myocarditis development also required donor… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-08
  • Infections and the relationship to treatment in neuromuscular autoimmunity.
    Infections and the relationship to treatment in neuromuscular autoimmunity. Muscle Nerve. 2017 Dec 06;: Authors: Prior DE, Nurre E, Roller SL, Kline D, Panara R, Stino AM, Davis JA, Freimer ML, Arnold WD Abstract INTRODUCTION: This study aimed to identify infections in patients with myasthenia gravis, dermatomyositis and chronic inflammatory demyelinating polyradiculoneuropathy and investigate the relationship between infection and immunomodulation. METHODS: A retrospective chart review examined 631 patients with myasthenia gravis (n=358), chronic inflammatory demyelinating polyradiculoneuropathy (n=124), and dermatomyositis (n=149) patients over a 10 year time period. RESULTS: Infection rates were similar at approximately 19% in all three diseases. Of the infections in which a causative organism was identified, pneumonia, sepsis, and opportunistic infections were leading diagnoses. A multivariate model demonstrated a significant association between infection and an increased dose of plasma exchange, mycophenolate mofetil, and corticosteroid therapy. DISCUSSION: There are few large studies investigating rates of infections in patients with autoimmune neuromuscular disorders and the relationship to immunomodulation. This study not only demonstrates the remarkably similar infection rates across the three diseases studied, but also shows their relationship to commonly used immunotherapies. This article is protected by copyright. All rights reserved.PMID: 29211921 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-07
  • MAIT Cells: A Link between Gut Integrity and Type 1 Diabetes.
    MAIT Cells: A Link between Gut Integrity and Type 1 Diabetes. Cell Metab. 2017 Dec 05;26(6):813-815 Authors: Gülden E, Palm N, Herold KC Abstract Type 1 diabetes (T1D) is a multifactorial autoimmune disease whose etiology involves complex interactions between the immune system and the intestinal microbiota. Recent studies by Rouxel et al. (2017) suggest that innate-like mucosal-associated invariant T cells (MAIT cells) may link gut integrity, the microbiota, and T1D.PMID: 29211981 [PubMed - in process] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-07
  • Metabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody disease.
    Related ArticlesMetabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody disease. Acta Neuropathol Commun. 2017 Dec 06;5(1):95 Authors: Jurynczyk M, Probert F, Yeo T, Tackley G, Claridge TDW, Cavey A, Woodhall MR, Arora S, Winkler T, Schiffer E, Vincent A, DeLuca G, Sibson NR, Isabel Leite M, Waters P, Anthony DC, Palace J Abstract The overlapping clinical features of relapsing remitting multiple sclerosis (RRMS), aquaporin-4 (AQP4)-antibody (Ab) neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-Ab disease mean that detection of disease specific serum antibodies is the gold standard in diagnostics. However, antibody levels are not prognostic and may become undetectable after treatment or during remission. Therefore, there is still a need to discover antibody-independent biomarkers. We sought to discover whether plasma metabolic profiling could provide biomarkers of these three diseases and explore if the metabolic differences are independent of antibody titre. Plasma samples from 108 patients (34 RRMS, 54 AQP4-Ab NMOSD, and 20 MOG-Ab disease) were analysed by nuclear magnetic resonance spectroscopy followed by lipoprotein profiling. Orthogonal partial-least squares discriminatory analysis (OPLS-DA) was used to identify significant differences in the plasma metabolite concentrations and produce models (mathematical algorithms) capable of identifying these diseases. In all instances, the models were highly discriminatory, with a distinct metabolite pattern identified for each disease. In addition, OPLS-DA identified AQP4-Ab NMOSD patient samples with low/undetectable antibody levels with an accuracy of 92%. The AQP4-Ab NMOSD metabolic profile was characterised by decreased levels of scyllo-inositol and small high density lipoprotein particles along… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-07
  • Rituximab for corticosteroid-resistant relapsing IgG4-related intracranial pachymeningitis: report of two cases.
    Related ArticlesRituximab for corticosteroid-resistant relapsing IgG4-related intracranial pachymeningitis: report of two cases. Pract Neurol. 2017 Dec 05;: Authors: Mageau A, Shor N, Fisselier M, Aboab J, Lecler A, Rebours C, Adle-Biassette H, Gout O, Deschamps R Abstract IgG4-related disease is now recognised as an important cause of intracranial and spinal hypertrophic pachymeningitis. Treatment with corticosteroids generally leads to significant clinical improvement. We present two cases of IgG4 pachymeningitis unresponsive to corticosteroids who improved with rituximab.PMID: 29208730 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-07
  • Regulation and dysregulation of axon infrastructure by myelinating glia.
    Related ArticlesRegulation and dysregulation of axon infrastructure by myelinating glia. J Cell Biol. 2017 Dec 04;216(12):3903-3916 Authors: Pan S, Chan JR Abstract Axon loss and neurodegeneration constitute clinically debilitating sequelae in demyelinating diseases such as multiple sclerosis, but the underlying mechanisms of secondary degeneration are not well understood. Myelinating glia play a fundamental role in promoting the maturation of the axon cytoskeleton, regulating axon trafficking parameters, and imposing architectural rearrangements such as the nodes of Ranvier and their associated molecular domains. In the setting of demyelination, these changes may be reversed or persist as maladaptive features, leading to axon degeneration. In this review, we consider recent insights into axon-glial interactions during development and disease to propose that disruption of the cytoskeleton, nodal architecture, and other components of axon infrastructure is a potential mediator of pathophysiological damage after demyelination.PMID: 29114067 [PubMed - indexed for MEDLINE] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-07
  • Ocular manifestations of IgG4-related disease in children. More common than anticipated? Review of the literature and case report.
    Related ArticlesOcular manifestations of IgG4-related disease in children. More common than anticipated? Review of the literature and case report. Clin Rheumatol. 2017 Dec 04;: Authors: Smerla RG, Rontogianni D, Fragoulis GE Abstract IgG4-related disease (IgG4-RD) is an entity with various clinical manifestations. Histopathologically, it is characterized by lymphoplasmacytic infiltrates enriched in IgG4 (+) plasmacytes and usually fibrosis of the affected tissue. Most of the patients have also increased IgG4 serum levels and they respond to glucocorticosteroids. In children, due to its rare occurrence, IgG4-RD is ill defined. From the published studies, so far, it appears that ocular manifestations are very common in the paediatric population with IgG4-RD. Herein, we describe a new case of a child with IgG4-RD with ocular involvement manifested with orbit and eyelid swelling, successfully treated with steroids. In addition, we review the clinical, laboratory, histopathologic and radiologic characteristics of the published paediatric cases with IgG4-RD and ocular involvement, critically comparing them with the characteristics of the adult population. It seems that ocular manifestations are more frequently observed in children than in adults. Also, the pattern of involvement is different, with extraocular muscles and soft tissues being more commonly affected than the lacrimal glands.PMID: 29204759 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-06
  • Seroprevalence of lymphatic filariasis among migrant workers in Peninsular Malaysia.
    Seroprevalence of lymphatic filariasis among migrant workers in Peninsular Malaysia. Trans R Soc Trop Med Hyg. 2017 Dec 01;:1-3 Authors: Noordin R, Mohd Zain SN, Yunus MH, Sahimin N Abstract Background: Malaysia aims to eliminate lymphatic filariasis (LF) by the year 2020, thus the potential threat of LF from migrant workers needs to be investigated. Methods: Brugian and bancroftian filariasis among 484 migrant workers from six countries were investigated using rapid tests based on detection of specific IgG4 antibodies against BmR1 (Brugia Rapid) and BmSXP recombinant antigens. Results: The seroprevalence of brugian filariasis was very low; however, bancroftian filariasis was notable among workers from India, Nepal and Myanmar. Conclusion: Malaysia is not endemic for Wuchereria bancrofti, but harbors the vectors for the parasite, thus the results showed that migrant workers should be monitored for this infection.PMID: 29206992 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-06
  • Vitamin B12 association with mAbs: Mechanism and Potential Mitigation Strategies.
    Vitamin B12 association with mAbs: Mechanism and Potential Mitigation Strategies. Biotechnol Bioeng. 2017 Dec 02;: Authors: Du C, Martin R, Huang Y, Borwankar A, Tan Z, West J, Singh N, Borys M, Ghose S, Ludwig R, Tao L, Li ZJ Abstract Process control for manufacturing biologics is critical for ensuring product quality, safety and lot to lot consistency of therapeutic proteins. In this study, we investigated the root cause of the pink coloration observed for various in-process pools and drug substances in the antibody manufacturing process. Vitamin B12 is covalently bound to mAbs via a cobalt-sulfur coordinate bond via the cysteine residues. The vitamin B12 was identified to attach to an IgG4 molecule at cysteine residues on light chain (Cys-214), and heavy chain (Cys-134, Cys-321, Cys-367 and Cys-425). Prior to attachment to mAbs, the vitamin B12 needs to be in its active form of hydroxocobalamin. During culture media preparation, storage and cell culture processing, cyanocobalamin, the chemical form of vitamin B12 added to media, is converted to hydroxocobalamin by white fluorescence light (about 50% degradation in 11-14 days at room temperature and with room light intensity about 500-1,000 lux) and by short-wavelength visible light (400-550 nm). However, cyanocobalamin is stable under red light (wavelength > 600 nm) exposure and does not convert to hydroxocobalamin. Our findings suggests that the intensity of pink color depends on concentrations of both free sulfhydryl groups on reduced mAb and hydroxocobalamin, the active form of vitamin B12 . Both reactants are necessary and neither one… ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-06
  • [IgG4-related kidney disease: Urologist trap?]
    Related Articles[IgG4-related kidney disease: Urologist trap?] Prog Urol. 2017 Dec 01;: Authors: Tricard T, Addeo P, Sauvinet G, Mouracadé P, Lindner V, Le Van Quyen P, Roy C, Lang H, Bachellier P PMID: 29203156 [PubMed - as supplied by publisher] ... leer mas
    Fuente: CIENCIA – INOREADERPublicado en: 2017-12-06