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Antibodies HLA

Byung Ha Chung, Jeong Ho Kim, Bum Soon Choi, Cheol Whee Park, Ji-Il Kim, In Sung Moon, Yong-Soo Kim, Yeong Jin Choi, Eun-Jee Oh, Chul Woo Yang
Background/Aims: This study investigated the clinical significance of detecting anti-human leukocyte antigen-donor specific antibody (HLA-DSA) in kidney transplant recipients (KTRs) requiring indication biopsy owing to allograft dysfunction. Methods: We analyzed the presence of HLA-DSA in 210 KTRs who took indication biopsy. We divided these cases into two groups, HLA-DSA (+) (n = 52) and HLA-DSA (-) (n = 158) group, and compared the clinical characteristics, pathological findings, and clinical outcomes of the two groups...
October 20, 2016: Korean Journal of Internal Medicine
Monika Lindemann, Marina Zaslavskaya, Melanie Fiedler, Benjamin Wilde, Falko M Heinemann, Andreas Heinold, Peter A Horn, Oliver Witzke
Approximately 70% of kidney transplant recipients are non-responders to conventional hepatitis B virus (HBV) vaccines. We examined whether Fendrix(™) , an HBV vaccine containing 3-O-desacyl-4'-monophosphoryl lipid A (MPL) as adjuvant, could induce HBV immunity in these patients and compared their vaccination efficacy with healthy controls tested previously by the same assays. We selected 35 kidney transplant recipients who had been vaccinated at least thrice against HBV but had never displayed anti-HBs antibodies...
October 20, 2016: Scandinavian Journal of Immunology
Leonid Dubrovsky, Elliott Joseph Brea, Dmitry Pankov, Emily Casey, Tao Dao, Cheng Liu, David A Scheinberg
Specific immunotherapy for acute leukemia remains a great unmet need. Native unmodified monoclonal antibody therapies, while promising, are inadequately effective for these malignancies, and multiple mechanisms for failure have been described. Antibody-dependent cellular cytotoxicity or phagocytosis is the primary modality of mAb-mediated cell killing in vivo, but ultimately leads to relapse of the leukemias, in model systems and in humans. By use of a T-cell receptor mimic mAb ESKM, derived against a WT1 peptide expressed in complex with HLA-A*02:01, whose only mechanism of therapeutic action is ADCC, we evaluated the mechanisms of leukemic relapse from its potent therapeutic action in mouse xenograft models of human leukemia...
2016: Oncoimmunology
Isabella Guzzo, Federica Morolli, Francesca Diomedi Camassei, Antonina Piazza, Elvira Poggi, Luca Dello Strologo
BACKGROUND: Several cases of severe antibody-mediated rejection (AMR) secondary to antibodies against the angiotensin II type 1 receptor (AT1R-Ab) have been described with variable outcome. CASE-DIAGNOSIS/TREATMENT: We report the case of a 13-year-old boy whose first kidney transplant failed due to steroid-resistant acute cellular rejection, with the subsequent development of sensitization. He received a second kidney transplant which was complicated by early humoral rejection, with weakly positive staining for the complement degradation product C4d...
October 17, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Maria Malm, Kirsi Tamminen, Timo Vesikari, Vesna Blazevic
Norovirus (NoV) is a leading cause of acute gastroenteritis in people of all ages worldwide. NoV-specific serum antibodies which block the binding of NoV virus-like particles (VLPs) to the cell receptors have been thoroughly investigated. In contrast, only a few publications are available on the NoV capsid VP1 protein-specific T cell responses in humans naturally infected with the virus. Freshly isolated peripheral blood mononuclear cells of eight healthy adult human donors previously exposed to NoV were stimulated with purified VLPs derived from NoV GII...
2016: Frontiers in Microbiology
Bor-Show Tzang, Szu-Yi Chiang, Hsu-Chin Chan, Chung-Hsien Liu, Tsai-Ching Hsu
Human parvovirus B19 (B19) is harmful during pregnancy since it can be vertically transmitted to the developing fetus. In addition, the anti‑B19 antibodies induced by B19 infection are believed to have a cytopathic role in B19 transmission; however, knowledge regarding the effects of anti‑B19 antibodies during pregnancy is limited. To investigate the possible roles of anti‑B19 antibodies during pregnancy, the present study examined the effects of anti‑B19‑VP1 unique region (VP1u), anti‑B19‑VP2 and anti‑B19‑nonstructural protein 1 (NS1) immunoglobulin G (IgG) antibodies on BeWo trophoblasts...
September 26, 2016: Molecular Medicine Reports
Susanna Sainio, Kaija Javela, Jarno Tuimala, Katri Haimila
Lack of reliable laboratory parameters is the main challenge in the management of fetal and neonatal alloimmune thrombocytopenia (FNAIT). Despite the long-known association between the HLA-DRB3*01:01 allele and human platelet antigen 1a (HPA-1a) alloimmunisation, maternal human leucocyte antigen (HLA) typing has been of little clinical value. Recently, other DRB3 allele variants have been suggested to predict the severity of FNAIT. In this nationwide population-based retrospective cohort study, we performed extensive HLA typing of 96 women, accounting for 87% of our cohort of 110 families with confirmed or possible HPA-1a-immunisation...
October 17, 2016: British Journal of Haematology
Annie Elong Ngono, Hui-Wen Chen, William W Tang, Yunichel Joo, Kevin King, Daniela Weiskopf, John Sidney, Alessandro Sette, Sujan Shresta
Infection with one of the four dengue virus serotypes (DENV1-4) presumably leads to lifelong immunity against the infecting serotype but not against heterotypic reinfection, resulting in a greater risk of developing Dengue Hemorrhagic Fever/Dengue Shock Syndrome (DHF/DSS) during secondary infection. Both antibodies and T cell responses have been implicated in DHF/DSS pathogenesis. According to the T cell-based hypothesis termed "original antigenic sin," secondary DENV infection is dominated by non-protective, cross-reactive T cells that elicit an aberrant immune response...
October 7, 2016: EBioMedicine
David K Packham, Ian R Fraser, Peter G Kerr, Karen R Segal
BACKGROUND: Diabetic nephropathy is the most common cause of end stage renal failure. We assessed the safety, tolerability, and explored therapeutic effects of adult allogeneic bone-marrow derived mesenchymal precursor cells (MPC) in patients with moderate to severe diabetic nephropathy. METHODS: Multicenter, randomized, double-blind, dose-escalating, sequential, placebo-controlled trial assessing a single intravenous (IV) infusion of allogeneic MPC (United States adopted name: rexlemestrocel-L) 150×10(6) (n=10), 300×10(6) (n=10) or placebo (n=10) in adults with diabetic nephropathy with an estimated glomerular filtration rate (eGFR) 20-50ml/min/1...
September 17, 2016: EBioMedicine
Nataša Katalinić, Marina Fućak, Tajana Crnić, Milena Ćurković, Alma Starčević, Sanja Balen
BACKGROUND: The introduction of more sensitive techniques, such as Luminex® for HLA antibody screening of patients awaiting organ transplantation has resulted in a better understanding of transplantation immunology and improvements in clinical practice. OBJECTIVE: The interpretation of the results obtained only by Luminex® can lead to inaccurate evaluation of a patient's antibody status and unjustified rejection of a potential organ donor. The aim of this study was to demonstrate the benefits of performing HLA antibody screening in the sera of patients on the waiting list for organ transplantation by two different assays, complement dependent cytotoxicity (CDC) and Luminex®...
October 14, 2016: Wiener Klinische Wochenschrift
Luca Dello Strologo, Luisa Murer, Isabella Guzzo, Federica Morolli, Annalisa M V Pipicelli, Elisa Benetti, Germana Longo, Sara Testa, Andrea Ricci, Fabrizio Ginevri, Luciana Ghio, Massimo Cardillo, Antonina Piazza, Alessandro Nanni Costa
BACKGROUND: High levels of preformed anti-HLA antibodies dramatically diminish renal transplant outcomes. Most desensitization programmes guarantee good intermediate outcomes but quite disappointing long-term prognosis. The search for a fully compatible kidney increases time on the waiting list. METHODS: In February 2011, a nationwide hyperimmune programme (NHP) was begun in Italy: all available kidneys are primarily proposed to highly sensitized patients with a panel reactive antibody above 80%...
October 14, 2016: Nephrology, Dialysis, Transplantation
Jeffrey Ma, Anita Patel, Kathryn Tinckam
This review paper discusses the impact of de novo donor-specific antibodies (DSA) to donor HLA antigens in kidney transplantation and summarizes the benefits and challenges that exist with DSA monitoring. Post-transplant DSA is associated with worse allograft outcomes and its detection may precede or coincide with clinical, biochemical, and histologic allograft dysfunction. There are no absolute features of DSA testing results that perfectly discriminate between states of disease and health. In a state of antibody-associated graft dysfunction, removal or reduction in DSA may only provide clinical benefit for some...
September 2016: Advances in Chronic Kidney Disease
Anna K Le Fevre, Marjorie M Walker, Amir Hadjiashrafy, Rani Bhatia, Joerg Mattes, Nicholas J Talley, Scott Nightingale
OBJECTIVES: This study compared the clinical and histopathological characteristics of children with EoE and elevated anti-transglutaminase (TTG Ab) with those with EoE and normal TTG Ab titres. METHODS: Single center chart and blinded histopathological review of patients diagnosed with EoE over a four-year period, who had esophageal and duodenal biopsies taken at time of endoscopy, and TTG Ab measured within 6 months of biopsy. Patients with histology-proven CD were excluded...
October 12, 2016: Journal of Pediatric Gastroenterology and Nutrition
Ercan Mıhçı, Banu Güzel Nur, Sibel Berker-Karaüzüm, Aygen Yılmaz, Reha Artan
Celiac disease is an autoimmune, gastrointestinal disorder characterized by intolerance to the dietary grain protein gluten. An increased prevalence of celiac disease has been reported in Down syndrome and Turner syndrome, but there has been only few previous reports with respect to the association of celiac disease in Williams-Beuren syndrome. The aim of this study was to evaluate the frequency of celiac disease in our 24 Williams-Beuren syndrome patients. Gastrointestinal problems and celiac disease symptoms of patients were noted...
November 2015: Turkish Journal of Pediatrics
Prabitha Natarajan, Jingchun Liu, Manjula Santhanakrishnan, David R Gibb, Lewis M Slater, Jeanne E Hendrickson
BACKGROUND: Few therapeutic options currently exist to prevent or to mitigate transfusion-associated red blood cell (RBC) alloimmunization. We hypothesized that bortezomib, a proteasome inhibitor currently being utilized for HLA alloantibody and ADAMTS13 autoantibody reduction, may be beneficial in a transfusion setting. Herein, we utilized a reductionist murine model to test our hypothesis that bortezomib would decrease RBC alloimmune responses. STUDY DESIGN AND METHODS: Wild-type mice were treated with bortezomib or saline and transfused with murine RBCs expressing the human KEL glycoprotein...
October 13, 2016: Transfusion
Gamze Isitman, Alexandra Tremblay-McLean, Irene Lisovsky, Julie Bruneau, Bertrand Lebouché, Jean-Pierre Routy, Nicole F Bernard
Natural Killer (NK) cell education, which requires the engagement of inhibitory NK cell receptors (iNKRs) by their ligands, is important for generating self-tolerant functional NK cells. While the potency of NK cell education is directly related to their functional potential upon stimulation with HLA null cells, the influence of NK cell education on the potency of the antibody dependent cellular cytotoxicity (ADCC) function of NK cells is unclear. ADCC occurs when the Fc portion of an immunoglobulin G antibody bridges the CD16 Fc receptor on NK cells and antigen on target cells, resulting in NK cell activation, cytotoxic granule release, and target cell lysis...
2016: PloS One
Priya D Shanmugarajah, Nigel Hoggard, Stuart Currie, Daniel P Aeschlimann, Pascale C Aeschlimann, Dermot C Gleeson, Mohammed Karajeh, Nicola Woodroofe, Richard A Grünewald, Marios Hadjivassiliou
BACKGROUND: Alcohol-related cerebellar degeneration is one of the commonest acquired forms of cerebellar ataxia. The exact pathogenic mechanisms by which alcohol leads to cerebellar damage remain unknown. Possible autoreactive immune mediated mechanisms have not been explored previously. In this study, we aim to investigate the potential role of alcohol-induced immune mediated cerebellar degeneration. METHODS: Patients with ataxia and a history of alcohol misuse were recruited from the Ataxia and Hepatology tertiary clinics at Sheffield Teaching Hospitals NHS Trust...
2016: Cerebellum & Ataxias
Rin Ogiya, Naoki Niikura, Nobue Kumaki, Giampaolo Bianchini, Shigehisa Kitano, Takayuki Iwamoto, Naoki Hayashi, Kozue Yokoyama, Risa Oshitanai, Mayako Terao, Toru Morioka, Banri Tsuda, Takuho Okamura, Yuki Saito, Yasuhiro Suzuki, Yutaka Tokuda
The presence of tumour-infiltrating lymphocytes (TILs) is associated with favourable long-term outcome in breast cancer. However, little is known about changes in TILs during metastatic progression. To confirm our hypothesis that malignant tumours escape from the host immune system during metastasis, we evaluated the percentage of TILs in paired samples of primary and metastatic breast tumours. We retrospectively identified 25 patients with human epidermal growth factor receptor-2 (HER2)-positive (n = 14, HER2+) and triple negative (n = 11, TN) early breast cancer diagnosed during 1990-2009 at Tokai University Hospital and who subsequently experienced regional or distant recurrence confirmed by tumour biopsy/resection...
October 11, 2016: Cancer Science
Ryo Ishida, Akira Shimizu, Takashi Kitani, Mayumi Nakata, Noriyoshi Ota, Hiroshi Kado, Yayoi Shiotsu, Mami Ishida, Keiichi Tamagaki
A 30-year-old woman with myelodysplastic syndrome underwent allogeneic hematopoietic stem cell transplantation (HSCT) derived from her HLA-matched sister six years previously. She received preconditioning total body irradiation with renal shielding and was subsequently administered cyclosporin A (CyA) as prophylaxis against graft-versus-host disease (GVHD). Four months after HSCT, asymptomatic proteinuria and glomerular hematuria developed during CyA tapering without obvious extrarenal involvements of GVHD, and persisted for six years...
2016: Internal Medicine
Jorge Malheiro, Sandra Tafulo, Leonídio Dias, La Salete Martins, Isabel Fonseca, Idalina Beirão, António Castro-Henriques, António Cabrita
Detrimental impact of preformed donor-specific antibodies (DSA) against human leukocyte antigens on outcomes after kidney transplantation remains controversial. We aimed to study DSA characteristics (strength and C1q-binding) that might distinguish harmful DSA from clinically irrelevant ones. We retrospectively studied 60 kidney-transplanted patients with preformed DSA detected by single antigen beads (SAB) assays (IgG and C1q kits). Patients were divided both by DSA strength (MFI < vs. ≥15000) and C1q-binding ability...
October 7, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
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