Hydroxychloroquine efficiently suppresses inflammatory responses of human class-switched memory B cells via Toll-like receptor 9 inhibition

Publication date: Available online 4 July 2018
Source:Clinical Immunology
Author(s): Masataka Torigoe, Kei Sakata, Akina Ishii, Shigeru Iwata, Shingo Nakayamada, Yoshiya Tanaka
Hydroxychloroquine is widely used for autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Although B cells contribute to the pathogenesis of these diseases, the action of hydroxychloroquine on B cells remains unclear. Here we examined the effects of hydroxychloroquine on functions of B cell subsets. Hydroxychloroquine efficiently inhibited the mammalian target of rapamycin complex 1, differentiation of CD19⁺IgD⁻CD27⁺ class-switched memory B cells to plasmablasts and their IgG production, under stimulation with CpG, a Toll-like receptor (TLR)-9 ligand. Hydroxychloroquine also inhibited CpG-induced production of interleukin-6 and tumor necrosis factor-α in B cell subsets. Taken together, hydroxychloroquine markedly suppresses the TLR9-mediated human B cell functions during inflammatory processes. Based on our results, we believe that hydroxychloroquine can be beneficial in the treatment of B cell-mediated autoimmune diseases.



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Hematological Malignancies Associated With Primary Immunodeficiency Disorders

Publication date: September 2018
Source:Clinical Immunology, Volume 194
Author(s): Lucy Duan, Eyal Grunebaum
Primary Immunodeficiency disorders (PID) have been increasingly recognized in association with hematologic malignancies. To better appreciate this association, a systemic search of the Ovid MEDLINE database was performed with terms related of hematologic malignancies and all PID described in the 2017 International Union of Immunological Societies Expert Committee for Primary Immunodeficiency. More than 60 PID distinct PID, caused by cell-intrinsic and extrinsic mechanisms were associated with diverse hematologic malignancies. These occurred among all subgroups of PID, including syndromic and non-syndromic combined PID affecting cellular and humoral immunity, predominantly antibody deficiencies and defects of immune regulation. In addition, defects in phagocyte numbers or functions, or in innate immunity were associated with hematologic malignancies. Increased awareness and vigilance for the possibility of malignancy is required when caring for patients with PID.



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Intensive Care to Facilitate Organ Donation: A Report on the Experience of 2 Spanish Centers with A Common Protocol\

Background The aim of this study is to report the experience with a program of Intensive Care to facilitate Organ Donation (ICOD) in 2 Spanish centers based on a common protocol. Methods Retrospective review of clinical charts of patients with a devastating brain injury whose families were approached to discuss the possibility of ICOD once further treatment was deemed futile by the treating team. Study period: 1/1/2011-12/31/2015. Results ICOD was discussed with families of 131 patients. Mean age of possible donors was 75 (SD=11) years. The main cause of brain injury was an intracranial hemorrhage (72%). Interviews with families were held after the decision had been made not to intubate/ventilate in 50% of cases, and after the decision not to continue with invasive ventilation in the remaining cases. Most interviews (66%) took place in the emergency department. The majority of families (95%) consented to ICOD. Of the 125 consented cases, 101 (81%) developed brain death (BD), most in ≤72 hours. Ninety-nine patients (98%) transitioned to actual donation after BD, with 1.2 organs transplanted per donor. Of patients who did not evolve to BD, 4 died following an unexpected cardiac arrest and 18 after the withdrawal of life-sustaining measures. ICOD contributed to 33% of actual donors registered at both centers. Conclusions ICOD is well accepted by families. Most patients evolve to BD within a short period of time. The practice substantially contributes to increasing organ donation and offers more patients the chance of donating their organs after death. CORRESPONDENCE INFORMATION: Beatriz Domínguez-Gil, MD, PhD. Director General, Organización Nacional de Trasplantes. C/Sinesio Delgado 6, pabellón 3, 28029 Madrid, Spain, Email: bdominguez@msssi.es AUTHORSHIP PAGE: FMS, JMPV and BDG conceived and designed the study. FMS, LMC and JMPV contributed with the data required for the study. EC and BDG coordinated the data collection and undertook the statistical analysis. JLM, AFC and PM participated in the performance of the research. FMS, JMPV and BDG drafted the first version of the paper, with contributions from the rest of the authors. The authors declare no conflict of interests. The study received no external funding. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Donor Derived Viral Infections in Liver Transplantation

Donor-derived infections are defined as any infection present in the donor that is transmitted to 1 or more recipients. Donor-derived infections can be categorized into 2 groups: 'expected' and 'unexpected' infections. Expected transmissions occur when the donor is known to have an infection, such as positive serology for CMV, EBV or hepatitis B core antibody, at the time of donation. Unexpected transmissions occur when a donor has no known infection prior to donation, but 1 or more transplant recipients develop an infection derived from the common donor. Unexpected infections are estimated to occur in far less than 1% of solid organ transplant recipients. We will review the epidemiology, risk factors and approaches to prevention and management of donor-derived viral infectious disease transmission in liver transplantation. *Co-First Authors Corresponding Author: Michael G. Ison, MD MS FIDSA FAST, Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, 645 N Michigan Avenue Suite 900, Chicago, Illinois 60611, 312-695-4186 (Office), 312-695-5088 (Fax). mgison@northwestern.edu Authorship Page Hannah Nam, MD and Kathy M Nilles, MD are co-first authors. Both have made substantial contributions in gathering information necessary in drafting the article, participated in writing the article, and revised it critically for important intellectual content. Josh Levitsky, MD MS and Michael G Ison, MD MS have revised the article critically for important intellectual content and gave final approval of the version to be submitted, as well as any revised versions. Disclosures: HN and KMN have nothing to disclose. JL is a paid speaker for Gilead and Novartis. MGI has received support for research, paid to Northwestern University from Beckman Coulter, Cephied, Chimerix, Emergent BioScience, Gilead, Janssen, and Shire; compensated consultation from Chimerix, Celltrion, Genentech/Roche, MediVector, Seqirus, Shionogi, and VirBio; and paid membership of DSMB from GlaxoSmithKlein, Shionogi. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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The First Kidney Transplant in Ireland

No abstract available

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Minimally invasive transplantation of primary human hepatocyte inserts that facilitate vascularization

No abstract available

https://ift.tt/2KMO83Y

TACROLIMUS INDUCED CHOLESTATIC HEPATITIS IN A PATIENT WITH LIVER TRANSPLANT

No abstract available

https://ift.tt/2ISL9SA