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Diabetes and ctla-4

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https://www.readbyqxmd.com/read/27424137/cytotoxic-t-lymphocyte-antigen-4-gene-variants-in-type-2-diabetic-patients-with-or-without-neuropathy
#1
Javad Kiani, Saedeh Khadempar, Mehrdad Hajilooi, Hamzeh Rezaei, Fatemeh Keshavarzi, Ghasem Solgi
Many studies have shown that cytotoxic T lymphocyte antigen-4 (CTLA-4) gene variants are associated with several autoimmune diseases particularly type 1 diabetes. Due to the lack of consistent data for this association with type 2 diabetes (T2D), this study explored the possible influence of CTLA-4 gene polymorphisms at -1722 (T/C), -318 (C/T), and +49 (G/A) positions for susceptibility to T2D in relation with neuropathy. One hundred and eleven unrelated patients with T2D [49 patients with diabetic peripheral neuropathy (DPN) and 62 patients without PDN] and 100 healthy ethnic- and gender-matched controls were included in this study...
June 2016: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/27357431/altered-regulatory-t-cell-phenotype-in-latent-autoimmune-diabetes-of-the-adults-lada
#2
M Radenkovic, C Silver, J Arvastsson, K Lynch, Å Lernmark, R A Harris, C-D Agardh, C M Cilio
Latent autoimmune diabetes of the adults (LADA) accounts for up to 12% of all patients with diabetes. Initially the disease resembles type 2 diabetes (T2D); however, the typical presence of β cell autoantibodies indicates an autoimmune basis of LADA. While dysfunctional regulatory T cells (Tregs ) have been implicated in autoimmune diabetes, these cells have been scarcely studied in LADA. The aim of this study was to investigate the frequency and phenotype of circulating Tregs in LADA patients early during disease progression...
October 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27328412/reparixin-a-cxcr1-2-inhibitor-in-islet-allotransplantation
#3
Rena L Pawlick, John Wink, Andrew R Pepper, Antonio Bruni, Nasser Abualhassen, Yasmin Rafiei, Boris Gala-Lopez, Mariusz Bral, A M James Shapiro
Quality of life in Type 1 diabetic patients may be improved with islet transplantation, but lifelong immunosuppression is required to prevent rejection. Allo-immune response is a key player in graft dysfunction and although the adaptive immune response is well characterized, the effect of the innate immune reaction after transplantation is only recently becoming appreciated. In this study, we address how the innate response affects long-term outcomes in a murine islet allotransplant model. CTLA-4 Ig treatment is known to significantly prolong kidney subcapsular islet allograft survival and enhance glucose tolerance...
September 2, 2016: Islets
https://www.readbyqxmd.com/read/27210268/progress-and-challenges-for-treating-type-1-diabetes
#4
REVIEW
Justin W Garyu, Eric Meffre, Chris Cotsapas, Kevan C Herold
It has been more than 30 years since the initial trials of Cyclosporin A to treat patients with new onset Type 1 diabetes (T1D). Since that time, there have been insights into genetic predisposition to the disease, the failures of immune tolerance, and mechanisms that cause the immune mediated β cell destruction. The genetic loci associated affect lymphocyte development and tolerance mechanisms. Discoveries related to the roles of specific immune responses gene such as the major histocompatibility complex, PTPN22, CTLA-4, IL-2RA, as well as the mechanisms of antigen presentation in the thymus have suggested ways in which autoreactivity may follow changes in the functions of these genes that are associated with risk...
July 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/26644313/a-patient-with-ctla-4-haploinsufficiency-presenting-gastric-cancer
#5
Seiichi Hayakawa, Satoshi Okada, Miyuki Tsumura, Sonoko Sakata, Yoshitaka Ueno, Kohsuke Imai, Tomohiro Morio, Osamu Ohara, Kazuaki Chayama, Masao Kobayashi
Cytotoxic T-lymphocyte-antigen 4 (CTLA-4) is an essential negative regulator expressed on regulatory T cells (Tregs) and activated T cells. Germline heterozygous mutations in CTLA4 lead to haploinsufficiency of CTLA-4, resulting in the development of an autosomal dominant immune dysregulation syndrome with incomplete penetrance. We report here a Japanese patient with this disorder who has a novel heterozygous single nucleotide insertion, 76_77insT (p. L28SfsX40), in the CTLA4 gene. Peripheral blood mononuclear cells from the patient showed decreased frequency of CTLA-4(high) cells in CD4(+)FOXP3(+) cells following CD3/CD28 stimulation...
January 2016: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/26615100/regulatory-t-cells-in-autoimmune-diabetes-mechanisms-of-action-and-translational-potential
#6
REVIEW
Vitalijs Ovcinnikovs, Lucy S K Walker
Since the discovery of specialized T cells with regulatory function, harnessing the power of these cells to ameliorate autoimmunity has been a major goal. Here we collate the evidence that regulatory T cells (Treg) can inhibit Type 1 diabetes in animal models and humans. We discuss the anatomical sites and molecular mechanisms of Treg suppressive function in the Type 1 diabetes setting, citing evidence that Treg can function in both the pancreatic lymph nodes and within the pancreatic lesion. Involvement of the CTLA-4 pathway, as well as TGF-β and IL-2 deprivation will be considered...
2015: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/26612761/clustering-of-immunological-metabolic-and-genetic-features-in-latent-autoimmune-diabetes-in-adults-evidence-from-principal-component-analysis
#7
Giovanni Mario Pes, Alessandro Palmerio Delitala, Alessandra Errigo, Giuseppe Delitala, Maria Pina Dore
Latent autoimmune diabetes in adults (LADA) which accounts for more than 10 % of all cases of diabetes is characterized by onset after age 30, absence of ketoacidosis, insulin independence for at least 6 months, and presence of circulating islet-cell antibodies. Its marked heterogeneity in clinical features and immunological markers suggests the existence of multiple mechanisms underlying its pathogenesis. The principal component (PC) analysis is a statistical approach used for finding patterns in data of high dimension...
June 2016: Internal and Emergency Medicine
https://www.readbyqxmd.com/read/26587547/association-between-genetic-variants-and-diabetes-mellitus-in-iranian-populations-a-systematic-review-of-observational-studies
#8
REVIEW
Mehrnoosh Khodaeian, Samaneh Enayati, Ozra Tabatabaei-Malazy, Mahsa M Amoli
INTRODUCTION: Diabetes mellitus as the most prevalent metabolic disease is a multifactorial disease which is influenced by environmental and genetic factors. In this systematic review, we assessed the association between genetic variants and diabetes/its complications in studies with Iranian populations. METHODS: Google Scholar, PubMed, Scopus, and Persian web databases were systematically searched up to January 2014. The search terms were "gene," "polymorphism," "diabetes," and "diabetic complications"; nephropathy, retinopathy, neuropathy, foot ulcer, and CAD (coronary artery diseases); and Persian equivalents...
2015: Journal of Diabetes Research
https://www.readbyqxmd.com/read/26546236/ctla-4-49-a-g-polymorphism-and-antiglutamic-acid-decarboxylase-antibody-associated-encephalopathy-in-taiwanese-children
#9
Jainn-Jim Lin, Kuang-Lin Lin, Yu Wang, Huei-Shyong Wang, Shao-Hsuan Hsia, Luan-Yin Chang
BACKGROUND: Anti-glutamic acid decarboxylase antibodies are associated with encephalopathy, an autoimmune central nervous system inflammatory disease. The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)+49 A/G polymorphism has been shown to confer genetic susceptibility to positive anti-glutamic acid decarboxylase antibodies in patients with type 1 diabetes mellitus in Japan. We aimed to investigate the association of the CTLA-4+49 A/G (rs231775) polymorphism in Taiwanese children with anti-glutamic acid decarboxylase antibody-associated encephalopathy...
April 2016: Brain & Development
https://www.readbyqxmd.com/read/26450994/a-snp-in-the-immunoregulatory-molecule-ctla-4-controls-mrna-splicing-in-vivo-but-does-not-alter-diabetes-susceptibility-in-the-nod-mouse
#10
Fabian Jakubczik, Ken Jones, Jennifer Nichols, William Mansfield, Anne Cooke, Nick Holmes
CTLA-4 is a critical "checkpoint" regulator in autoimmunity. Variation in CTLA-4 isoform expression has been linked to type 1 diabetes development in human and NOD mouse studies. In the NOD mouse, a causative link between increased expression of the minor isoform ligand-independent CTLA-4 and a reduction in diabetes has become widely accepted. Altered splicing of CTLA-4 has been attributed to a single nucleotide polymorphism (SNP) in Ctla4 exon2 (e2_77A/G). To investigate this link, we have used NOD embryonic stem (ES) cells to generate a novel NOD transgenic line with the 77A/G SNP...
January 2016: Diabetes
https://www.readbyqxmd.com/read/26436934/-autoimmune-diseases-in-type-1a-diabetes-mellitus
#11
REVIEW
Aldo Ferreira-Hermosillo, Mario Antonio Molina-Ayala
Type 1A diabetes (DM1A) is an autoimmune disease that comprises 10% of patients with diabetes mellitus. Its frequency is gradually increasing in countries like Mexico. Patients with DM1A commonly have hypothyroidism, Addison disease, celiac disease and less common diseases such as polyglandular syndrome. These diseases are related to susceptibility genes such as HLA, CTLA-4 and PTPN22, which induce central and peripheral immunologic tolerance. This review article emphasizes the importance of searching other autoimmune diseases in patients with DM1A, to improve their prognosis and quality of life...
August 2015: Revista Médica de Chile
https://www.readbyqxmd.com/read/26311302/induction-of-tolerance-and-prolongation-of-islet-allograft-survival-by-syngeneic-hematopoietic-stem-cell-transplantation-in-mice
#12
Shi-feng Yang, Wu-jun Xue, Wan-hong Lu, Li-yi Xie, Ai-ping Yin, Jin Zheng, Ji-ping Sun, Yang Li
BACKGROUNDS: Syngeneic or autologous hematopoietic stem cells transplantation (HSCT) has been proposed to treat autoimmune diseases because of its immunosuppressive and immunomodulatory effects, which can also contribute to posttransplant antirejection therapy. In this study, we explored the tolerogenic effect of syngeneic HSCT on prolonging islet allograft survival. METHODS: C57BL/6 mice received syngeneic HSCT plus preconditioning with sublethal irradiation. Then islets of BALB/c mice were transplanted into the renal subcapsular of C57BL/6 mice after chemically induced into diabetes...
October 2015: Transplant Immunology
https://www.readbyqxmd.com/read/26051683/investigation-of-ctla-4-318c-t-gene-polymorphism-in-cases-with-type-1-diabetes-of-azerbaijan-northwest-iran
#13
Shohreh Almasi, Mohammad Reza Aliparasti, Akbar Aliasgarzadeh, Bahareh Abd-Nikfarjam, Heikki Hyöty, Mikael Knip, Hadi Feizi, Amirbabak Sioofy-Khojine, Badrossadat Rahnama
This study analyzed the association of CTLA-4-318C/T gene polymorphism with susceptibility, clinical course and laboratory findings of Type 1 diabetes (T1D). One hundred and fifty-three T1D patients and 189 healthy controls entered this study. CTLA-4-318C/T genotyping was performed by tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) analysis. The allelic and genotypic frequencies of -318C/T gene polymorphism were similar in patients and controls. However, younger age, earlier age at onset, higher HbA1c levels, higher frequency of Glutamic acid decarboxylase antibodies (GADA) and Insulinoma Associated-2 Autoantibodies (IA-2A) were observed in T1D patient carriers of CT genotype...
August 2015: Immunology Letters
https://www.readbyqxmd.com/read/25936594/genome-wide-identification-of-new-genes-and-pathways-in-patients-with-both-autoimmune-thyroiditis-and-type-1-diabetes
#14
Yaron Tomer, Lawrence M Dolan, George Kahaly, Jasmin Divers, Ralph B D'Agostino, Giuseppina Imperatore, Dana Dabelea, Santica Marcovina, Mary Helen Black, Catherine Pihoker, Alia Hasham, Sara Salehi Hammerstad, David A Greenberg, Vaneet Lotay, Weijia Zhang, Maria Cristina Monti, Nina Matheis
Autoimmune thyroid diseases (AITD) and Type 1 diabetes (T1D) frequently occur in the same individual pointing to a strong shared genetic susceptibility. Indeed, the co-occurrence of T1D and AITD in the same individual is classified as a variant of the autoimmune polyglandular syndrome type 3 (designated APS3v). Our aim was to identify new genes and mechanisms causing the co-occurrence of T1D + AITD (APS3v) in the same individual using a genome-wide approach. For our discovery set we analyzed 346 Caucasian APS3v patients and 727 gender and ethnicity matched healthy controls...
June 2015: Journal of Autoimmunity
https://www.readbyqxmd.com/read/25754913/immunoregulatory-molecules-in-patients-with-gestational-diabetes-mellitus
#15
Karen Priscilla Tezotto Pendeloski, Rosiane Mattar, Maria Regina Torloni, Caio Perez Gomes, Sandra Maria Alexandre, Silvia Daher
Induction of maternal-fetal immune tolerance is essential for the development of normal pregnancy. Impaired expression of costimulatory molecules may lead to intense inflammatory reaction, a mechanism involved in the pathophysiology of gestational diabetes mellitus (GDM). The aim of this study was to investigate whether immunoregulatory molecules are involved in the physiopathology of GDM. This case-control study included 30 healthy pregnant women and 20 GDM patients. Flow cytometry was used to assess peripheral blood T subpopulations (CD4(+) and CD8(+)), the expression of immunoregulatory molecules (CD28, ICOS, CTLA-4, and PD-1) and activation markers (CD69 and HLA-DR)...
September 2015: Endocrine
https://www.readbyqxmd.com/read/25634360/low-dose-interleukin-2-fosters-a-dose-dependent-regulatory-t-cell-tuned-milieu-in-t1d-patients
#16
RANDOMIZED CONTROLLED TRIAL
Michelle Rosenzwajg, Guillaume Churlaud, Roberto Mallone, Adrien Six, Nicolas Dérian, Wahiba Chaara, Roberta Lorenzon, S Alice Long, Jane H Buckner, Georgia Afonso, Hang-Phuong Pham, Agnès Hartemann, Aixin Yu, Alberto Pugliese, Thomas R Malek, David Klatzmann
Most autoimmune diseases (AID) are linked to an imbalance between autoreactive effector T cells (Teffs) and regulatory T cells (Tregs). While blocking Teffs with immunosuppression has long been the only therapeutic option, activating/expanding Tregs may achieve the same objective without the toxicity of immunosuppression. We showed that low-dose interleukin-2 (ld-IL-2) safely expands/activates Tregs in patients with AID, such HCV-induced vasculitis and Type 1 Diabetes (T1D). Here we analyzed the kinetics and dose-relationship of IL-2 effects on immune responses in T1D patients...
April 2015: Journal of Autoimmunity
https://www.readbyqxmd.com/read/25523632/extension-of-the-cd4%C3%A2-%C2%BAfoxp3%C3%A2-%C2%BAcd25-low-regulatory-t-cell-subpopulation-in-type-1-diabetes-mellitus
#17
András Zóka, Gábor Barna, Anikó Somogyi, Györgyi Műzes, Ágnes Oláh, Zahra Al-Aissa, Orsolya Hadarits, Katalin Kiss, Gábor Firneisz
Regulatory T-cells (Treg) have a crucial role in limiting physiologic autoreactivity. Foxp3 is a master regulator transcription factor of Treg differentiation and active Treg cells express high levels of IL-2 receptor α-chain (CD25). The aim of our study was to assess the key markers of Treg cell function in type 1 diabetic (T1DM) and control subjects by flow cytometry. The proportion of CD25(-/low) cells among CD4(+)Foxp3(+) Treg cells was higher in T1DM patients that might suggest a shifted proportion of the incomplete/reserve and the fully active (CD4(+)Foxp3(+)CD25(+)) Treg cell subpopulations in T1DM, similarly to other Th1-mediated autoimmune diseases...
2015: Autoimmunity
https://www.readbyqxmd.com/read/25416723/long-term-follow-up-of-ipilimumab-induced-hypophysitis-a-common-adverse-event-of-the-anti-ctla-4-antibody-in-melanoma
#18
RANDOMIZED CONTROLLED TRIAL
Frédérique Albarel, Caroline Gaudy, Frédéric Castinetti, Tiphaine Carré, Isabelle Morange, Bernard Conte-Devolx, Jean-Jacques Grob, Thierry Brue
OBJECTIVE: Few data are published on the long-term follow-up of ipilimumab-induced hypophysitis, a cytotoxic T-lymphocyte antigen 4 antibody. We characterized hypophysitis in terms of clinical signs, endocrinological profile, and imaging at diagnosis and during a long-term follow-up. DESIGN AND PATIENTS: Fifteen patients, treated for malignant melanoma and who presented ipilimumab-induced hypophysitis, were observed between June 2006 and August 2012 in Timone Hospital, Marseille...
February 2015: European Journal of Endocrinology
https://www.readbyqxmd.com/read/25407554/blockade-of-the-activation-of-t-cells-around-%C3%AE-cell-by-the-targeted-ctla-4-ig-at-the-surface-of-%C3%AE-cell
#19
Wei Qu, Lin Li, Chendong Han, Meihua Li, Jing Wang, Chaohui Yin, Jing Zhang, Zhaoshun Jiang
Diabetes mellitus affects 347 million people worldwide, and over 80 % of diabetes deaths occur in low- and middle-income countries. Type 1 diabetes (T1D) is characterized by the attacks of the body's own immune system on the pancreatic β-cells. In this work, we present a new CTLA-4 Ig targeting at the surface of β-cell and prepare it from Escherichia coli aiming at clearing activated T cells around β-cells and avoiding all-round decline in systematic immunity. This fusion protein is composed of CTLA-4-Ig part and β-cell-targeting part, with properties of the therapeutic effect of CTLA-4-Ig and selective binding to β-cells...
March 2015: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/25364772/ex-vivo-expanded-autologous-polyclonal-regulatory-t-cells-suppress-inhibitor-formation-in-hemophilia
#20
Debalina Sarkar, Moanaro Biswas, Gongxian Liao, Howard R Seay, George Q Perrin, David M Markusic, Brad E Hoffman, Todd M Brusko, Cox Terhorst, Roland W Herzog
Adoptive cell therapy utilizing ex vivo expanded polyclonal CD4(+)CD25(+)FOXP3(+) regulatory T cells (Treg) is in use in clinical trials for the treatment of type 1 diabetes and prevention of graft vs host disease in bone marrow transplantation. Here we seek to evaluate this approach in the treatment of inherited protein deficiencies, i.e. hemophilia, which is often complicated by antibody formation against the therapeutic protein. Treg from mice that express GFP-marked FoxP3 were highly purified by two-step magnetic/flow sorting and ex vivo expanded 50- to 80-fold over a 2-week culture period upon stimulation with antibody-coated microbeads...
July 30, 2014: Molecular Therapy. Methods & Clinical Development
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