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immunodeficiency diseases

Kimberley M Zorn, Thomas R Lane, Daniel P Russo, Alex M Clark, Vadim Makarov, Sean Ekins
The human immunodeficiency virus (HIV) causes over a million deaths every year and has a huge economic impact in many countries. The first class of drugs approved were nucleoside reverse transcriptase inhibitors. A newer generation of reverse transcriptase inhibitors have become susceptible to drug resistant strains of HIV, and hence alternatives are urgently needed. We have recently pioneered the use of Bayesian machine learning to generate models with public data to identify new compounds for testing against different disease targets...
February 19, 2019: Molecular Pharmaceutics
C Lehmann, J Malin, I Suárez, G Fätkenheuer
Human immunodeficiency virus (HIV) infection has become a chronic disease with a favourable prognosis if adequate antiretroviral therapy (ART) is applied. Therefore, each patient with HIV infection should be treated irrespectively of clinical symptoms or of immunological status. A combination of three active drugs that have to be taken life-long has been standard for many years. The regimen contains two nucleoside reverse transcriptase inhibitors plus either an integrase inhibitor, a boosted protease inhibitor, or a non-nucleoside reverse transcriptase inhibitor...
February 18, 2019: Der Internist
Markus G Seidel, Gerhard Kindle, Benjamin Gathmann, Isabella Quinti, Matthew Buckland, Joris van Montfrans, Raphael Scheible, Stephan Rusch, Lukas M Gasteiger, Bodo Grimbacher, Nizar Mahlaoui, Stephan Ehl
Patient registries are instrumental for clinical research in rare diseases. They help to achieve a sufficient sample size for epidemiological and clinical research and to assess the feasibility of clinical trials. The European Society for Immunodeficiencies (ESID) registry currently comprises information on >25,000 patients with inborn errors of immunity (IEI). The prerequisite of a patient to be included into the ESID registry is an IEI either defined by a defect in a gene included in the disease classification of the international union of immunological societies (IUIS), or verified by applying clinical criteria...
February 15, 2019: Journal of Allergy and Clinical Immunology in Practice
Inga Tometten, Kerstin Felgentreff, Manfred Hönig, Fabian Hauck, Michael H Albert, Tim Niehues, Ruy Perez, Sujal Ghosh, Capucine Picard, Jan Stary, Renata Formankova, Austen Worth, Pere Soler-Palacín, Marina García-Prat, Luis M Allende, Luis Ignacio Gonzalez-Granado, Polina Stepensky, Silvia Di Cesare, Alessia Scarselli, Caterina Cancrini, Carsten Speckmann, Kimberly Gilmour, Luigi Notarangelo, Stephan Ehl, Jan Rohr
Severe combined immunodeficiencies (SCID) comprise a group of genetic diseases characterized by abrogated development of T lymphocytes. In some case reports of atypical SCID patients elevated proportions of γδ T lymphocytes have been reported. However, it is unknown whether these γδ T cells modulate or reflect the patient's clinical phenotype. We investigated the frequency of elevated γδ T cell proportions and associations with clinical disease manifestations in a cohort of 76 atypical SCID patients. Increased proportions of γδ T lymphocytes were present in approximately 60% of these patients...
February 15, 2019: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Omar Bushara, Daniel Miller, Alessio Giubellino, Matthew Schomaker, Bharat Thyagarajan, Andrew C Nelson
Epidermodysplasia Verruciformis (EV) is a rare skin disease characterized by the development of multiple flat warts with the potential for malignant transformation. Patients are susceptible to Human Papilloma Virus (HPV) infection that develops in a background of either a genetic or acquired immunodeficiency predisposing patients to infection with specific HPV types that are ubiquitous but generally non-pathogenic in healthy individuals. There is no standard clinical methodology for determining the causative HPV from patients with suspected EV...
February 17, 2019: Journal of Cutaneous Pathology
Leonid Bunimovich, Longmei Shu
Some basic aspects of the recently discovered phenomenon of local immunodeficiency [1] generated by antigenic cooperation in cross-immunoreactivity (CR) networks are investigated. We prove that local immunodeficiency (LI) that's stable under perturbations already occurs in very small networks and under general conditions on their parameters. Therefore our results are applicable not only to Hepatitis C where CR networks are known to be large [1], but also to other diseases with CR. A major necessary feature of such networks is the non-homogeneity of their topology...
February 14, 2019: Mathematical Biosciences
Stefano Volpi, Maria Pia Cicalese, Paul Tuijnenburg, Anton T J Tool, Eloy Cuadrado, Hamid Ahanchian, Raed Alzyoud, Zeynep Coban Akdemir, Federica Barzaghi, Alexander Blank, Bertrand Boisson, Cristina Bottino, Roberta Caorsi, Jean-Laurent Casanova, Sabrina Chiesa, Ivan Kingyue Chinn, Gregor Dückers, Anselm Enders, Hans Christian Erichsen, Lisa R Forbes, Tomasz Gambin, Marco Gattorno, Ehsan Ghayoor Karimiani, Silvia Giliani, Michael S Gold, Marwan Abu-Halaweh, Immacolata Brigida, Eva-Maria Jacobsen, Machiel H Jansen, Jovanka R King, Ronald M Laxer, James R Lupski, Emily Mace, Stefania Marcenaro, Reza Maroofian, Alexander B Meijer, Tim Niehues, Luigi D Notarangelo, Jordan Orange, Ulrich Pannicke, Chris Pearson, Paolo Picco, Patrick J Quinn, Ansgar Schulz, Filiz Seeborg, Asbjørg Stray-Pedersen, Hasan Tawamie, Ester M M van Leeuwen, Alessandro Aiuti, Rae Yeung, Klaus Schwarz, Taco W Kuijpers
We report the natural history, clinical manifestations, genetics, and immunohematological findings in 14 patients from 11 families with ARPC1B deficiency, delineating the spectrum of the disease that appears progressive and challenging to manage clinically.
February 13, 2019: Journal of Allergy and Clinical Immunology
Hsin-Yun Sun, Haruka Uemura, Ngai-Sze Wong, Denise Pui-Chung Chan, Bonnie Chun-Kwan Wong, Pi-Han Lin, Li-Hsin Su, Chien-Ching Hung, Shinichi Oka, Sui-Yuan Chang, Shui-Shan Lee
BACKGROUND: Acute hepatitis C virus (HCV) infections have been increasingly reported among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) in the Asia-Pacific region. It remains unknown whether international network of HCV transmission has occurred in this region. METHODS: HIV-positive patients with acute HCV infection, defined as HCV seroconversion within a year or documented acute hepatitis with seroconversion, diagnosed in Hong Kong, Taipei, and Tokyo during 2010-2016 were included in this molecular epidemiology study...
February 16, 2019: Liver International: Official Journal of the International Association for the Study of the Liver
Eman Teer, Danzil E Joseph, Natasha Driescher, Theo Nell, Leanne Dominick, Natasha Midgley, Gaurang Deshpande, Martin Page, Etheresia Pretorius, Nicholas J Woudberg, Sandrine Lecour, Richard H Glashoff, M Faadiel Essop
Although rollout of combined anti-retroviral treatment (cART) has blunted human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) onset, there is increased development of cardiovascular diseases (CVD) in HIV-infected individuals. While most HIV-infected individuals on cART achieve viral suppression, this may not necessarily result in complete immunological recovery. This study therefore evaluated T cell-mediated changes and coagulation markers in HIV-positive individuals to ascertain their potential to increase CVD risk...
February 15, 2019: American Journal of Physiology. Heart and Circulatory Physiology
Brian J Morris, Catherine A Hankins, Joya Banerjee, Eugenie R Lumbers, Adrian Mindel, Jeffrey D Klausner, John N Krieger
Background: Male circumcision (MC) is proven to substantially reduce men's risk of a number of sexually transmitted infections (STIs). We conducted a detailed systematic review of the scientific literature to determine the relationship between MC and risk of STIs and associated conditions in women. Methods: Database searches by "circumcision women" and "circumcision female" identified 68 relevant articles for inclusion. Examination of bibliographies of these yielded 14 further publications...
2019: Frontiers in Public Health
Francesco Giuseppe Garaci, Erald Vasili, Francesco Bocchinfuso, Adriano Lacchè, Vittorio Nardone, Carlo Di Donna, Luigi Spiritigliozzi, Roberto Floris
Nowadays tuberculosis has become a reemerging infectious disease due to the many forms of immunodeficiency. Patients with eating disorders like anorexia nervosa and bulimia are a susceptible group due to the immune impairment correlated with severe malnutrition and their prevalence and incidence is growing. We describe the case of a 31-year-old woman, with long-standing history of anorexia nervosa and bulimia, diagnosed with advanced pulmonary tuberculosis. This case underlines the importance on never neglecting even the slightest symptoms in patients with malnutrition and never excluding this pathology without a proper investigation...
March 2019: Radiology case reports
David B Beck, Ivona Aksentijevich
Monogenic autoinflammatory disorders are a group of conditions defined by systemic or localized inflammation without identifiable causes, such as infection. In contrast to classical primary immunodeficiencies that manifest with impaired immune responses, these disorders are due to defects in genes that regulate innate immunity leading to constitutive activation of pro-inflammatory signaling. Through studying patients with rare autoinflammatory conditions, novel mechanisms of inflammation have been identified that bare on our understanding not only of basic signaling in inflammatory cells, but also of the pathogenesis of more common inflammatory diseases and have guided treatment modalities...
2019: Frontiers in Immunology
Pedro Eman, Eduardo Chacon, Meera Gupta, Jonathan C Berger, Malay B Shah, Hanine E El Haddad, Amr El-Husseini, Anna C Dela Cruz, Alla Grigorian, Xiaonan Mei, Roberto Gedaly
BACKGROUND: We aimed to study outcomes in HIV + patients with HCC in the US following Liver Transplantation (LT) using the UNOS dataset. METHODS: The database was queried from 2003 to 2016 for patients undergoing LT with HCC, HIV+, and HCC/HIV+. RESULTS: Out of 17,397 LT performed for HCC during the study period, 113 were transplanted for HCC with HIV infection (91 isolated livers). Patients transplanted for HCC/HIV+ were younger (55.54 ± 5...
February 11, 2019: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
İlknur Külhaş Çelik, Ersoy Civelek, Ayşe Metin, Tayfur Giniş, Müge Toyran, Emine Dibek Mısırlıoğlu, Can Naci Kocabaş
Background/aim: Ig level assessment is frequently used in the diagnosis and follow-up of immunodeficiency, as well as in studies investigating the prevalence of low serum Ig level in specific diseases. Materials and methods: Patients who underwent Ig testing in the inpatient and outpatient clinics of our hospital in the years 2010–2016 were included. The Ig levels of the patients were assessed separately according to two reference systems commonly used in Turkey and another reference system used in the USA...
February 11, 2019: Turkish Journal of Medical Sciences
Krystelle Nganou-Makamdop, Daniel C Douek
During human immunodeficiency virus (HIV) infection, type I interferon (IFN-I) signaling induces an antiviral state that includes the production of restriction factors that inhibit virus replication, thereby limiting the infection. As seen in other viral infections, type I IFN can also increase systemic immune activation which, in HIV disease, is one of the strongest predictors of disease progression to acquired immune deficiency syndrome (AIDS) and non-AIDS morbidity and mortality. Moreover, IFN-I is associated with CD4 T cell depletion and attenuation of antigen-specific T cell responses...
February 14, 2019: Virologica Sinica
Robert van Domselaar, Duncan T Njenda, Rohit Rao, Anders Sönnerborg, Kamalendra Singh, Ujjwal Neogi
Human immunodeficiency virus type 1 subtype C (HIV-1C) has a natural deletion of a YPxL motif in its Gag-p6 late domain. This domain mediates the binding of Gag to host cell protein ALIX and subsequently facilitates viral budding. In a subset of HIV-1C infected individuals, the tetrapeptide insertion PYxE has been identified at the deleted YPxL motif site. Here, we report the consequences of PYxE insertion on the interaction with ALIX and the relevance regarding replication fitness and drug sensitivity. In our three HIV-1C cohorts, PYKE and PYQE were most prevalent among PYxE variants...
February 13, 2019: Journal of Virology
G Evers, M Thrull, H Wittkowski, L H Schmidt, M Mohr
Clinical manifestations of primary immunodeficiency are heterogeneous, and early diagnosis is challenging. Leading symptoms are recurrent upper and lower respiratory tract infections. Response to antibiotic therapy is often reduced. Beside infectious complications autoimmunity, autoinflammation and malignant diseases occur frequently. About 50 % of all PID patients are diagnosed after childhood, and the main group are patients with primary antibody deficiencies. Treatment of choice is the immunoglobulin substitution and the prophylactic or therapeutic use of antibiotics...
February 2019: Pneumologie
Zemenu Tamir, Abdurahaman Seid, Haftay Haileslassie
BACKGROUND: Hematologic abnormalities involving peripheral blood cell cytopenias are strong predictors of morbidity, mortality and poor antiretroviral therapy (ART) outcomes of HIV infected individuals. However, limited studies are conducted in resource-limited settings of sub-Saharan Africa that have addressed the magnitude and associated factors of cytopenias. This study aimed to investigate the magnitude and associated factors of cytopenias among ART naïve HIV infected adult Ethiopians...
2019: PloS One
Lance T Vernon, Jason D Seacat, Catherine A Demko, Andre Paes B da Silva, Stephen J Zyzanski
AIMS: Periodontal diseases (PDs) affect nearly half of Americans ≥30 years old and are common in human immunodeficiency virus-positive (HIV+) adults. A validated measure of oral hygiene skill could improve tailored prevention-focused health communication. METHODS: We developed Oral Hygiene Skill Mastery (OHSIM), a provider-observed measure of toothbrushing and flossing ability. We examined OHSIM's inter-rater reliability (IRR) and concurrent validity using a blinded, cross-sectional study design with a convenience sample of HIV+/- adults...
February 13, 2019: Special Care in Dentistry
Matthew C Hernandez, John R Bergquist, Jennifer L Leiting, Tommy Ivanics, Lin Yang, Rory L Smoot, David M Nagorney, Mark J Truty
BACKGROUND: Patient-derived xenografts (PDX) are clinically relevant human cancer models that can be used to guide individualized medicine. We aimed to generate PDX models from clinically obtained biopsy specimens (surgical or image-guided) hypothesizing that low volume biopsy specimens could provide sufficient viable tissue to successfully engraft PDX models from patients with unresectable or metastatic disease. MATERIALS AND METHODS: We maintain a prospective high volume gastrointestinal malignancy PDX program...
February 12, 2019: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
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