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Joseph B Margolick, Jay H Bream, Tricia L Nilles, Huifen Li, Susan J Langan, Shane Deng, Ruibin Wang, Nikolas Wada, Sean X Leng
Background: Both aging and treated human immunodeficiency virus (HIV)-infected populations exhibit low-level chronic immune activation of unknown etiology, which correlates with morbidity and mortality. Cytomegalovirus (CMV) infection is common in both populations, but its relation to immune activation is unknown. Methods: T cells from men who have sex with men (22 virologically suppressed HIV+, 20 HIV-) were stimulated with peptides spanning 19 CMV open reading frames, and intracellular cytokine responses were assessed...
February 26, 2018: Journal of Infectious Diseases
Masakatsu Yamashita, Makoto Kuwahara
Although Bach2 (broad complex-tramtrack-bric a brac and Cap'n'collar homology 2) plays an important role in regulating Th2 cell differentiation and type-2 immune responses, the underlying molecular mechanisms remain unclear. Our current studies demonstrate that Bach2 associates with Batf (basic leucine zipper transcription factor ATF-like) family transcription factors and binds to the regulatory regions of the Th2 cytokine gene loci. The Bach2-Batf complex antagonizes the recruitment of the interferon regulatory factor 4 (Irf4)-containing Batf complex to activator protein 1 (AP-1) motifs in the Th2 cytokine gene locus and suppresses Th2 cytokine production and/or Th2 cell differentiation...
February 24, 2018: International Immunology
Anthony L Cunningham, Thomas C Heineman, Himal Lal, Olivier Godeaux, Roman Chlibek, Shinn-Jang Hwang, Janet E McElhaney, Timo Vesikari, Charles Andrews, Won Suk Choi, Meral Esen, Hideyuki Ikematsu, Martina Kovac Choma, Karlis Pauksens, Stéphanie Ravault, Bruno Salaun, Tino F Schwarz, Jan Smetana, Carline Vanden Abeele, Peter Van den Steen, Ilse Vastiau, Lily Yin Weckx, Myron J Levin
Background: The herpes zoster subunit vaccine (HZ/su), consisting of varicella-zoster virus glycoprotein E (gE) and AS01B Adjuvant System, was highly efficacious in preventing herpes zoster in the ZOE-50 and ZOE-70 trials ( NCT01165177; NCT01165229). We present immunogenicity results from those trials. Methods: Participants (ZOE-50: ≥50; ZOE-70: ≥70 years of age) received 2 doses of HZ/su or placebo, 2 months (M) apart. Serum anti-gE antibodies and CD4 T cells expressing ≥2 of the 4 activation markers assessed (CD42+) after stimulation with gE-peptides were measured in sub-cohorts for humoral (n=3293) and cell-mediated (n=466) immunogenicity...
February 26, 2018: Journal of Infectious Diseases
Mio Nakamura, Michael Abrouk, Benjamin Farahnik, Tian H Zhu, Tina Bhutani
The management of psoriatic disease in the human immunodeficiency virus (HIV)-positive population is challenging. The clinical course often is progressive and refractory; therefore, first- and second-line therapies including topical agents, phototherapy, and oral retinoids often are inadequate. Most other currently available systemic therapies for psoriatic disease are immunosuppressive, which poses a distinct clinical challenge. A comprehensive systematic review of the literature via a PubMed search of articles indexed for MEDLINE using the terms psoriasis and HIV and psoriatic arthritis and HIV combined with several systemic immunosuppressive agents yielded a total of 25 reported cases of systemic immunosuppressive therapies used to treat psoriatic disease in HIV-positive patients including methotrexate, cyclosporine, etanercept, adalimumab, infliximab, and ustekinumab...
January 2018: Cutis; Cutaneous Medicine for the Practitioner
Ross D Cranston, Michelle S Cespedes, Pawel Paczuski, Ming Yang, Robert W Coombs, Joan Dragavon, Alfred Saah, Catherine Godfrey, Jennifer Y Webster-Cyriaque, Elizabeth Y Chiao, Barbara Bastow, Timothy Wilkin
BACKGROUND: The quadrivalent human papillomavirus (HPV) vaccine (qHPV; types 6, 11, 16, 18) is indicated for men and women aged 9 to 26 years to prevent HPV associated anogenital high-grade squamous intraepithelial lesions (HSIL) and cancer. ACTG 5298 was a randomized placebo controlled Phase 3 study in human immunodeficiency virus (HIV)-infected men who have sex with men, and women of qHPV to prevent persistent anal HPV infection. Baseline data are presented here. METHODS: Human immunodeficiency virus-infected men who have sex with men, and women 27 years or older without previous anogenital or oral cancer were enrolled...
April 2018: Sexually Transmitted Diseases
Ebru N Cetin, Selda Sayin Kutlu, Osman Parca, Murat Kutlu, Gökhan Pekel
PURPOSE: To evaluate choroidal, macular, peripapillary retinal nerve fiber layer (RNFL) thicknesses and retinal vascular caliber alterations in HIV-1-infected patients without opportunistic infections. METHODS: This cross-sectional study included 45 HIV-1-infected patients and 47 healthy subjects. Spectral domain optical coherence tomography was used for assessment of choroidal, macular, peripapillary RNFL thicknesses and retinal vascular caliber alterations. RESULTS: The mean CD4 count was 426 ± 226 cells per milliliter and the mean HIV-1 RNA level was 1...
March 8, 2018: Retina
Masahiko Mori, Nuanjun Wichukchinda, Reiko Miyahara, Archawin Rojanawiwat, Panita Pathipvanich, Toshiyuki Miura, Michio Yasunami, Koya Ariyoshi, Pathom Sawanpanyalert
BACKGROUND: Class I HLA molecules contribute to HIV control through antigen presentation to both cytotoxic T lymphocytes (CTLs) and NK cells. Contribution of CTLs to HIV clinical outcome by HLA alleles has been well studied. However, reports about the role of NK cells in HIV clinical outcome, particularly, about the effect of HLA-KIR pairs, remain incomplete. METHODS: The effects of HLA allele-KIR pairs on HIV clinical outcome were statistically analyzed in a Thai cohort of treatment-naïve chronically infected (n=209)...
March 8, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Kristina Adachi, Jiahong Xu, Bonnie Ank, D Heather Watts, Margaret Camarca, Lynne M Mofenson, Jose Henrique Pilotto, Esau Joao, Glenda Gray, Gerhard Theron, Breno Santos, Rosana Fonseca, Regis Kreitchmann, Jorge Pinto, Marisa M Mussi-Pinhata, Daisy Maria Machado, Mariana Ceriotto, Mariza G Morgado, Yvonne J Bryson, Valdilea G Veloso, Beatriz Grinsztejn, Mark Mirochnick, Jack Moye, Karin Nielsen-Saines
BACKGROUND: Congenital cytomegalovirus (CMV) infection (cCMV) is an important cause of hearing loss and cognitive impairment. Prior studies suggest that HIV-exposed children are at higher risk of acquiring cCMV. We assessed the presence, magnitude, and risk factors associated with cCMV among infants born to HIV-infected women, who were not receiving antiretrovirals during pregnancy. METHODS: cCMV and urinary CMV load were determined in a cohort of infants born to HIV-infected women not receiving antiretrovirals during pregnancy...
March 9, 2018: Pediatric Infectious Disease Journal
Deniz Erturk-Hasdemir, Dennis L Kasper
Starting from birth, all animals develop a symbiotic relationship with their resident microorganisms that benefits both the microbe and the host. Recent advances in technology have substantially improved our ability to direct research toward the identification of important microbial species that affect host physiology. The identification of specific commensal molecules from these microbes and their mechanisms of action is still in its early stages. Polysaccharide A (PSA) of Bacteroides fragilis is the archetypical example of a commensal molecule that can modulate the host immune system in health and disease...
March 12, 2018: Annals of the New York Academy of Sciences
Anas Z Abidin, Adora M DSouza, Mahesh B Nagarajan, Lu Wang, Xing Qiu, Giovanni Schifitto, Axel Wismüller
HIV is capable of invading the brain soon after seroconversion. This ultimately can lead to deficits in multiple cognitive domains commonly referred to as HIV-associated neurocognitive disorders (HAND). Clinical diagnosis of such deficits requires detailed neuropsychological assessment but clinical signs may be difficult to detect during asymptomatic injury of the central nervous system (CNS). Therefore neuroimaging biomarkers are of particular interest in HAND. In this study, we constructed brain connectivity profiles of 40 subjects (20 HIV positive subjects and 20 age-matched seronegative controls) using two different methods: a non-linear mutual connectivity analysis approach and a conventional method based on Pearson's correlation...
2018: NeuroImage: Clinical
Daryl Ramai, Emmanuel Ofori, Sofia Nigar, Madhavi Reddy
Primary hepatic peripheral T-cell lymphoma (H-PTCL) is one of the rarest forms of non-Hodgkin lymphoma. We report a patient who presented with worsening jaundice, abdominal pain, and vomiting. Laboratory values were significant for elevated total bilirubin, alkaline phosphatase, and liver aminotransferases. Following a liver biopsy, histopathology revealed several large dense clusters of atypical T-lymphocytes which were CD2+, CD3+, CD5+, CD7-, CD4+, CD8-, CD56-, CD57-, CD30+ by immunohistochemistry. The proliferation index was approximately 70% by labeling for ki67/mib1...
February 27, 2018: World Journal of Hepatology
Jahnavi Aluri, Maya Gupta, Aparna Dalvi, Snehal Mhatre, Manasi Kulkarni, Gouri Hule, Mukesh Desai, Nitin Shah, Prasad Taur, Ramprasad Vedam, Manisha Madkaikar
Major histocompatibility complex (MHC) class II deficiency is a rare autosomal recessive form of primary immunodeficiency disorder (PID) characterized by the deficiency of MHC class II molecules. This deficiency affects the cellular and humoral immune response by impairing the development of CD4+ T helper (Th) cells and Th cell-dependent antibody production by B cells. Affected children typically present with severe respiratory and gastrointestinal tract infections. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy available for treating these patients...
2018: Frontiers in Immunology
Zahra Akbari, Mohammad Taheri, Abdorreza Jafari, Arezou Sayad
INTRODUCTION: Multiple sclerosis (MS) is a heterogeneous disease with an unknown etiology. Both genetic and environmental factors lead to MS disease. Recent studies have revealed the inhibitory role of T regulatory cells in the MS disease. Forkhead box P3 (FOXP3) gene is a transcript of the CD4+CD25+FOXP3 and T regulatory cells that is recently introduced as a factor in determining the lineage of immune cells. Based on these assumptions we investigate the expression of this gene in the peripheral blood of fifty MS patients in comparison to fifty controls...
February 27, 2018: Human Antibodies
Liannv Qiu, Yonglie Zhou, Qinhua Yu, Sujie Zheng, Zhenni Wang, Qiang Huang
Chronic lymphocytic leukaemia (CLL) is characterized by an abnormal expansion of mature B cells with variable progression. Follicular T helper (Tfh) cells help B cells differentiate into plasma cells or long-lived memory B cells in germinal centres (GCs). However, the role of Tfh cells in CLL is poorly understand, and whether it plays a critical role in disease progression in vivo is lacking. In this study, we investigate the dynamic change of circulating Tfh cells in peripheral blood from patients with CLL during the treatment periods to evaluate their utility to predict disease progression...
March 8, 2018: Immunology Letters
Xiaoyan Pan, Jian Lin, Xiaoyun Zeng, Wenjuan Li, Wenjiao Wu, Wan Zhen Lu, Jing Liu, Shuwen Liu
The persistent inflammation aggravated by a disordered immune response is considered to be the major cause of CD4+ T cell depletion in lymphoid tissue, which impels the progression of AIDS. Here, we report that heat shock factor 1 (HSF1) works as an innate repressor of HIV-induced inflammation. The activation of HSF1 was found to accompany inflammation during HIV infection. Further research uncovered that HSF1 activation inhibited HIV-induced inflammation. In addition, HSF1 overexpression suppressed the inflammatory response induced by HIV, while HSF1 deficiency exacerbated that inflammation...
January 31, 2018: Cellular Immunology
Han Jiang, Shijie Xin, Yumeng Yan, Yu Lun, Xiao Yang, Jian Zhang
BACKGROUND AND AIMS: Acetylation levels of FOXP3 could influence its expression level and SIRT1 is a deacetylase, which could regulate the acetylation level of FOXP3. We aimed to investigate the mechanism of Treg dysfunction, which might be caused by abnormal acetylation of FOXP3 regulated by SIRT1 in abdominal aortic aneurysm (AAA) patients. METHODS: Peripheral CD4+ T cells from AAA patients, abdominal aortic atherosclerotic occlusive disease (AOD) patients, and healthy donors (HC) were analyzed by flow cytometry to determine the percentage of CD4+ CD25+ Tregs and CD4+ CD25+ FOXP3+ T cells in CD4+ T cells...
February 14, 2018: Atherosclerosis
Tafadzwa Mlambo, Marianna Romito, Tatjana I Cornu, Claudio Mussolino
The development of tools which allow for the precise alterations of the epigenetic landscape in desired genomic locations presents exciting possibilities toward further understanding how gene expression is regulated and opportunities to harness these properties for therapeutic purposes. In contrast to gene knockout strategies, targeted epigenome modifications, such as editing of DNA methylation, can mediate gene expression modulation without changing the genomic sequence. Thereby, in a therapeutic context, this strategy may offer a safer route as compared to gene disruption using designer nucleases that, to reach high efficiencies, relies on the occurrence of random mutations to inactivate the target gene...
2018: Methods in Molecular Biology
Allison E Irvin, Gaurang Jhala, Yuxing Zhao, Timothy S Blackwell, Balasubramanian Krishnamurthy, Helen E Thomas, Thomas W H Kay
Type 1 diabetes is an autoimmune disease characterised by selective destruction of pancreatic beta cells by the immune system. The transcription factor nuclear factor-kappa B (NF-κB) regulates innate and adaptive immune responses. Using gene targeting and in vitro analysis of pancreatic islets and immune cells, NF-κB activation has been implicated in type 1 diabetes development. Here we use a non-obese diabetic (NOD) mouse model that expresses a luciferase reporter of transcriptionally active NF-κB to determine its activation in vivo during development of diabetes...
March 9, 2018: Scientific Reports
E D Pieterman, F G Liqui Lung, A Verbon, H I Bax, C W Ang, J Berkhout, G Blaauw, A Brandenburg, N D van Burgel, A Claessen, K van Dijk, M Heron, M Hooghiemstra, R Leussenkamp-Hummelink, E van Lochem, I H M van Loo, B Mulder, A Ott, O Pontesilli, A Reuwer, P Rombouts, V Saegeman, M Scholing, S Vainio, J E M de Steenwinkel
OBJECTIVES: The aim of this verification study was to compare the QuantiFERON® -TB Gold Plus (QFT-Plus) to the QuantiFERON® -TB Gold In Tube (QFT-GIT). The new QFT-Plus test contains an extra antigen tube which, according to the manufacturer additionally elicits a CD8+ T-cell response above the CD4+ T-cell response. We assessed the value of this tube in detecting recent latent tuberculosis infections. METHODS: Between May 2015 and December 2016, 1031 subjects underwent QFT-Plus and QFT-GIT test...
January 2018: Tuberculosis
Lei Ma, Haibo Xue, Ruiqun Qi, Yanqin Wang, Libing Yuan
BACKGROUND: Th17 cells and its effective cytokine IL-17A play an important role in the pathogenesis of abnormal immune responses in psoriasis. Notch1 signaling has been implicated in Th17 cell differentiation and function. In this study, our aim was to evaluate the possible inhibitory effect of Notch1 signaling inhibitor, γ-secretase inhibitor DAPT, on psoriatic Th17 cell differentiation and function in a mouse model of psoriasis-like skin inflammation. METHODS: Mouse psoriasis-like skin inflammation model was established by topical 5% imiquimod (IMQ) application, and experimental mice were divided into control group, IMQ-treated group and IM + DAPT-treated group...
March 10, 2018: Journal of Translational Medicine
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