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https://www.readbyqxmd.com/read/28815406/successful-management-of-a-hydropic-fetus-with-severe-anemia-and-thrombocytopenia-caused-by-anti-cd36-antibody
#1
Xiuzhang Xu, Lin Li, Wenjie Xia, Haoqiang Ding, Dawei Chen, Jing Liu, Jing Deng, Yangkai Chen, Zhiming He, Jiali Wang, Yuan Shao, Sentot Santoso, Xin Ye, Qun Fang
Cases of CD36 deficiency are not rare in Asian populations, foetal and neonatal alloimmune thrombocytopenia (FNAIT) caused by anti-CD36 isoantibodies appears more frequent than other HPA alloantibodies. However, little is known about the treatment of anti-CD36 mediated FNAIT in this region. A Chinese male foetus, whose mother had a history of multiple intrauterine foetal demise and/or hydrops, was diagnosed with severe FNAIT at 27 weeks of gestational age. Immunological analysis revealed total absence of CD36 on platelets and monocytes from mother, caused by a 329-330delAC mutation of the CD36 gene...
August 16, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28815218/capturing-the-systemic-immune-signature-of-a-norovirus-infection-an-n-of-1-case-study-within-a-clinical-trial
#2
Antony J Cutler, Joao Oliveira, Ricardo C Ferreira, Ben Challis, Neil M Walker, Sarah Caddy, Jia Lu, Helen E Stevens, Deborah J Smyth, Marcin L Pekalski, Jane Kennet, Kara M D Hunter, Ian Goodfellow, Linda S Wicker, John A Todd, Frank Waldron-Lynch
BACKGROUND:  The infection of a participant with norovirus during the adaptive study of interleukin-2 dose on regulatory T cells in type 1 diabetes (DILT1D) allowed a detailed insight into the cellular and cytokine immune responses to this prevalent gastrointestinal pathogen. METHODS:  Serial blood, serum and peripheral blood mononuclear cell (PBMC) samples were collected pre-, and post-development of the infection. To differentiate between the immune response to norovirus and to control for the administration of a single dose of aldesleukin (recombinant interleukin-2, rIL-2) alone, samples from five non-infected participants administered similar doses were analysed in parallel...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28815047/whole-blood-rna-transcript-based-models-can-predict-clinical-response-in-two-large-independent-clinical-studies-of-patients-with-advanced-melanoma-treated-with-the-checkpoint-inhibitor-tremelimumab
#3
Philip Friedlander, Karl Wassmann, Alan M Christenfeld, David Fisher, Chrisann Kyi, John M Kirkwood, Nina Bhardwaj, William K Oh
BACKGROUND: Tremelimumab is an antibody that blocks CTLA-4 and demonstrates clinical efficacy in a subset of advanced melanoma patients. An unmet clinical need exists for blood-based response-predictive gene signatures to facilitate clinically effective and cost-efficient use of such immunotherapeutic interventions. METHODS: Peripheral blood samples were collected in PAXgene® tubes from 210 treatment-naïve melanoma patients receiving tremelimumab in a worldwide, multicenter phase III study (discovery dataset)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28813660/neutralizing-antibody-responses-to-viral-infections-are-linked-to-the-non-classical-mhc-class-ii-gene-h2-ob
#4
Lisa K Denzin, Aly A Khan, Francesca Virdis, Jessica Wilks, Melissa Kane, Helen A Beilinson, Stanislav Dikiy, Laure K Case, Derry Roopenian, Michele Witkowski, Alexander V Chervonsky, Tatyana V Golovkina
Select humans and animals control persistent viral infections via adaptive immune responses that include production of neutralizing antibodies. The precise genetic basis for the control remains enigmatic. Here, we report positional cloning of the gene responsible for production of retrovirus-neutralizing antibodies in mice of the I/LnJ strain. It encodes the beta subunit of the non-classical major histocompatibility complex class II (MHC-II)-like molecule H2-O, a negative regulator of antigen presentation. The recessive and functionally null I/LnJ H2-Ob allele supported the production of virus-neutralizing antibodies independently of the classical MHC haplotype...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28811976/long-lived-pancreatic-ductal-adenocarcinoma-slice-cultures-enable-precise-study-of-the-immune-microenvironment
#5
Xiuyun Jiang, Y David Seo, Jae Hyuck Chang, Andrew Coveler, Eslam N Nigjeh, Sheng Pan, Florencia Jalikis, Raymond S Yeung, Ian N Crispe, Venu G Pillarisetty
Pancreatic ductal adenocarcinoma (PDA) remains a deadly disease that is rarely cured, despite many recent successes with immunotherapy for other malignancies. As the human disease is heavily infiltrated by effector T cells, we postulated that accurately modeling the PDA immune microenvironment would allow us to study mechanisms of immunosuppression that could be overcome for therapeutic benefit. Using viable precision-cut slices from fresh PDA, we developed an organotypic culture system for this purpose. We confirmed that cultured slices maintain their baseline morphology, surface area, and microenvironment after at least 6 d in culture, and demonstrated slice survival by MTT assay and by immunohistochemistry staining with Ki-67 and cleaved-Caspase-3 antibodies...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28807052/whole-blood-rna-transcript-based-models-can-predict-clinical-response-in-two-large-independent-clinical-studies-of-patients-with-advanced-melanoma-treated-with-the-checkpoint-inhibitor-tremelimumab
#6
Philip Friedlander, Karl Wassmann, Alan M Christenfeld, David Fisher, Chrisann Kyi, John M Kirkwood, Nina Bhardwaj, William K Oh
BACKGROUND: Tremelimumab is an antibody that blocks CTLA-4 and demonstrates clinical efficacy in a subset of advanced melanoma patients. An unmet clinical need exists for blood-based response-predictive gene signatures to facilitate clinically effective and cost-efficient use of such immunotherapeutic interventions. METHODS: Peripheral blood samples were collected in PAXgene® tubes from 210 treatment-naïve melanoma patients receiving tremelimumab in a worldwide, multicenter phase III study (discovery dataset)...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28806188/tubulointerstitial-nephritis-and-uveitis
#7
Kaivon Pakzad-Vaezi, Kathryn L Pepple
PURPOSE OF REVIEW: Tubulointerstitial nephritis and uveitis (TINU) is an important yet underrecognized ocular inflammatory syndrome. This review summarizes key historical publications that identified and defined the syndrome, and more recent literature that reveal the importance of urinary β2-microglobulin testing and kidney biopsy in the diagnostic evaluation of patients with TINU. Additionally, research studies providing new insights into disease pathogenesis are highlighted. RECENT FINDINGS: In contrast with initial reports of TINU manifesting exclusively as an anterior uveitis in pediatric patients, more recent reports have identified TINU in patients of all ages with a wide range of ocular manifestations...
August 12, 2017: Current Opinion in Ophthalmology
https://www.readbyqxmd.com/read/28802400/mycobacterium-tuberculosis-myma-is-a-tlr2-agonist-that-activate-macrophages-and-a-th1-response
#8
Iti Saraav, Swati Singh, Kirti Pandey, Monika Sharma, Sadhna Sharma
Cell wall of Mycobacterium tuberculosis (M.tb) is a major source of immunogenic proteins that can be tested as vaccine candidates. MymA (Rv3083), a 55 kDa M.tb flavin containing monooxygenase, is involved in modification of mycolic acids during acidic shock following M.tb internalization in macrophage. In this study, we have investigated the role of this cell wall associated protein in activation of macrophages by toll like receptor (TLRs) engagement and subsequent signaling. Our results showed that MymA stimulation of THP1 cells and human monocyte derived macrophages (MDM) lead to upregulation of TLR2 and co-stimulatory molecules CD40, CD80, CD86 and HLA-DR...
September 2017: Tuberculosis
https://www.readbyqxmd.com/read/28801345/molecular-basis-for-increased-susceptibility-of-indigenous-north-americans-to-seropositive-rheumatoid-arthritis
#9
Stephen W Scally, Soi-Cheng Law, Yi Tian Ting, Jurgen van Heemst, Jeremy Sokolove, Aaron J Deutsch, E Bridie Clemens, Antonis K Moustakas, George K Papadopoulos, Diane van der Woude, Irene Smolik, Carol A Hitchon, David B Robinson, Elizabeth D Ferucci, Charles N Bernstein, Xiaobo Meng, Vidyanand Anaparti, Tom Huizinga, Katherine Kedzierska, Hugh H Reid, Soumya Raychaudhuri, René E Toes, Jamie Rossjohn, Hani El-Gabalawy, Ranjeny Thomas
OBJECTIVE: The pathogenetic mechanisms by which HLA-DRB1 alleles are associated with anticitrullinated peptide antibody (ACPA)-positive rheumatoid arthritis (RA) are incompletely understood. RA high-risk HLA-DRB1 alleles are known to share a common motif, the 'shared susceptibility epitope (SE)'. Here, the electropositive P4 pocket of HLA-DRB1 accommodates self-peptide residues containing citrulline but not arginine. HLA-DRB1 His/Phe13β stratifies with ACPA-positive RA, while His13βSer polymorphisms stratify with ACPA-negative RA and RA protection...
August 11, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28797308/coeliac-disease-in-infants-antibodies-to-deamidated-gliadin-peptide-come-first
#10
Michele Arigliani, Francesca Rech Morassutti, Martina Fabris, Paola Melli, Elio Tonutti, Paola Cogo
BACKGROUND: The onset of coeliac disease (CD) in the first year of life is uncommon and the diagnosis can be challenging due to the suboptimal sensitivity of tissue transglutaminase antibodies (tTG) at this age and the many other possible causes of malabsorption in infants. Antibodies to deamidated gliadin peptides (anti-DGPs), especially IgG, may appear earlier than IgA anti-tTG in very young children with CD. CASE PRESENTATION: We report here on an 8-month-old child who was evaluated for failure to thrive, constipation and developmental delay...
August 10, 2017: Italian Journal of Pediatrics
https://www.readbyqxmd.com/read/28795147/impact-of-the-trough-level-of-calcineurin-inhibitor-on-the-prevalence-of-donor-specific-human-leukocyte-antigen-antibodies-during-long-term-follow-up-after-pediatric-liver-transplantation-antibody-strength-and-complement-binding-ability
#11
Kazuaki Tokodai, Shigehito Miyagi, Chikashi Nakanishi, Yasuyuki Hara, Wataru Nakanishi, Masafumi Goto, Michiaki Unno, Takashi Kamei
BACKGROUND: In pediatric patients, long-term immunosuppression after liver transplantation (LT) is typically minimal. However, posttransplant donor-specific HLA antibodies (DSAs) may be prevalent under these conditions. Here, we evaluated the effects of minimized calcineurin inhibitor (CNI) on DSA development to assess the validity of minimized/withdrawn immunosuppression. METHODS: We retrospectively examined 66 patients who underwent pediatric LT at our institution between July 1991 and October 2013...
August 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28792635/favorable-results-in-abo-incompatible-renal-transplantation-without-b-cell-targeted-therapy-advantages-and-disadvantages-of-rituximab-pretreatment
#12
Manabu Okada, Yoshihiko Watarai, Kenta Iwasaki, Kenta Murotani, Kenta Futamura, Takayuki Yamamoto, Takahisa Hiramitsu, Makoto Tsujita, Norihiko Goto, Shunji Narumi, Asami Takeda, Kunio Morozumi, Kazuharu Uchida, Takaaki Kobayashi
The effectiveness of desensitization with rituximab in ABO-incompatible renal transplantation (ABO-I) has been widely reported. However, ABO-I outcomes are still worse than those of ABO-identical or ABO-compatible renal transplantation (ABO-Id/C). We retrospectively examined the outcomes in consecutive living donor ABO-Id/C (n = 412) and ABO-I (n = 205) cases to elucidate the causes of inferiority in ABO-I. ABO-I cases included recipients treated with rituximab (RIT, n = 131), splenectomy (SPX, n = 21), or neither because of low anti-A/B antibody titers (NoR/S, n = 53)...
August 9, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28782692/deleterious-impact-of-c3d-binding-donor-specific-anti-hla-antibodies-after-pediatric-liver-transplantation
#13
Eduardo Couchonnal, Christine Rivet, Stéphanie Ducreux, Jérôme Dumortier, Alexie Bosch, Olivier Boillot, Sophie Collardeau-Frachon, Rémi Dubois, Valérie Hervieu, Patrice André, Jean-Yves Scoazec, Alain Lachaux, Valérie Dubois, Olivier Guillaud
BACKGROUND: The prevalence and clinical impact of anti-HLA donor-specific antibodies (DSA) after liver transplantation (LT) have not been extensively studied, especially in pediatric population. METHODS: The present cross-sectional study included 100 patients who underwent a first LT in childhood. Anti HLA immunization study was performed at a single time point during routine follow-up using Luminex® single antigen tests with classical anti-IgG conjugate and anti-C3d conjugate...
August 3, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28782523/monitoring-native-hla-i-trimer-specific-antibodies-in-luminex-multiplex-single-antigen-bead-assay-evaluation-of-beadsets-from-different-manufacturers
#14
Mepur H Ravindranath, Vadim Jucaud, Soldano Ferrone
Luminex single antigen bead (SAB) assay utilizes beadsets coated with a set of cloned and purified HLA molecules, for monitoring serum anti-HLA antibodies. Particularly, the level of serum IgG against native HLA-I trimers (heavy chain (HC) and β2-microglobulin (β2m) with a peptide), expressed in allograft tissues is correlated with graft failure. In addition to native trimeric HLAI, the beadsets may carry HC only or the dimeric variants, peptide-free HC with β2m and β2m-free HC with or without peptides...
August 4, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28782517/structural-analysis-of-owl-monkey-mhc-dr-shows-that-fully-protective-malaria-vaccine-components-can-be-readily-used-in-humans
#15
Carlos F Suárez, Laura Pabón, Ana Barrera, Jorge Aza-Conde, Manuel Alfonso Patarroyo, Manuel Elkin Patarroyo
More than 50 years ago the owl monkey (genus Aotus) was found to be highly susceptible to developing human malaria, making it an excellent experimental model for this disease. Microbes and parasites' (especially malaria) tremendous genetic variability became resolved during our malaria vaccine development, involving conserved peptides having high host cell binding activity (cHABPs); however, cHABPs are immunologically silent and must be specially modified (mHABPs) to induce a perfect fit into major histocompatibility complex (MHC) molecules (HLA in humans)...
August 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28782163/statin-associated-immune-mediated-necrotising-myopathy-a-new-zealand-case-series-showing-possible-over-representation-in-pacific-islanders
#16
Michelle Claudine Woolley, Simon Stebbings, John Highton
AIMS: To review incident cases of statin-associated immune mediated necrotising myopathy (IMNM) associated with anti-HMGCR antibodies in a single New Zealand centre, over a two year period. METHODS: Four incident cases of statin-associated IMNM were seen between 2014 and 2016. Their presentation, investigation, treatment and current response to treatment are summarised. Two of the four patients were Pacific Islanders despite a small pacific island population in the southern district health board (SDHB)...
August 7, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28777489/refinement-of-humoral-immune-monitoring-in-kidney-transplantation-the-role-of-hidden-alloreactive-memory-b-cells
#17
REVIEW
Sergi Luque, Marc Lúcia, Oriol Bestard
The advent of novel sensitive assays assessing circulating anti-HLA antibodies has allowed recognizing humoral alloimmunity as the main immune-mediated mechanism responsible of allograft rejection and graft loss in kidney transplantation. However, current immune-monitoring techniques, exclusively focusing on circulating anti-HLA antibodies, may underestimate the magnitude of humoral immune response as they exclude the memory B-cell (mBC) pool. Different biological compartments are involved in the intricate mechanisms triggering humoral alloimmune responses even in absence of detectable circulating alloantbodies...
August 4, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28777478/a-simplified-method-of-calculating-cpra-for-kidney-allocation-application-in-hong-kong
#18
Yuen Piu Chan, Monica Wing Kan Wong, Lydia Wing Mui Tang, Mengbiao Guo, Wanling Yang, Patrick Ip, Philip Kam Tao Li, Chi Bon Leung, Ka Foon Chau, Johnny Chi Kwong Lam, Nicholas Ka Ming Yeung, Janette Siu Yin Kwok
Calculated panel reactive antibody (cPRA) represents possibility of encountering an incompatible donor for organ transplant candidates, and has gradually replaced traditional PRA as a measurement of sensitization level. We tested two cPRA calculation methods on a cohort of renal candidate (n=613). HLA typing of 563 Chinese deceased renal donors were used to estimate allele and haplotype frequencies of Hong Kong donor pool. The OPTN formula was adopted to generate cPRA (cPRA(freq)). We also incorporated a computer script to compare unacceptable antigens of patients against HLA phenotype of donors...
August 4, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28776960/role-of-de-novo-donor-specific-anti-hla-antibodies-in-kidney-graft-failure-a-case-control-study
#19
Ana Castro, Jorge Malheiro, Sandra Tafulo, Leonídio Dias, La Salete Martins, Isabel Fonseca, Idalina Beirão, António Castro-Henriques, António Cabrita
The role of de novo donor-specific anti-HLA antibodies (dnDSA) within the pathways leading to graft failure remains not fully understood. We investigated 56 patients who were transplanted between 2002-2014 with kidney graft failure (cases), for a possible association of development of dnDSA with graft failure. The 56 patients with failed transplants were matched with 56 patients with a functioning graft at present for the variables deceased or living donor, transplant number, transplant year, recipient age and gender, donor age and gender, dialysis vintage time, transplant induction therapy...
August 4, 2017: HLA
https://www.readbyqxmd.com/read/28771838/human-regulatory-macrophages-are-potent-in-suppression-of-the-xenoimmune-response-via-indoleamine-2-3-dioxygenase-involved-mechanism-s
#20
Fei Guo, Min Hu, Dandan Huang, Yuanfei Zhao, Benjamin Heng, Gilles Guillemin, Chai K Lim, Wayne J Hawthorne, Shounan Yi
BACKGROUND: For xenotransplantation to truly succeed, we must develop immunomodulatory strategies to suppress the xenoimmune response but by minimizing immunosuppression over the long term. Regulatory macrophages (Mreg) have been shown to suppress polyclonal T-cell proliferation in vitro and prolong allograft survival in vivo. However, the question of whether they are capable of suppressing xenoimmune responses remains unknown. This study assessed the potential of human Mreg to be used as an effective immunomodulatory method in xenotransplantation...
August 2, 2017: Xenotransplantation
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