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Check point autoimmunity

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https://www.readbyqxmd.com/read/28929192/role-of-pd-1-in-immunity-and-diseases
#1
Kenji Chamoto, Muna Al-Habsi, Tasuku Honjo
Immunity developed to defend our bodies from foreign particles, including bacteria and viruses. Although effector cells responsible for acquired immunity, mainly T cells, and B cells, are able to distinguish self from non-self, they sometimes attack the body's tissues because of imperfect central tolerance. Several immune check points developed to limit overactivation of these cells. One of the most important immune checkpoints is programmed cell death-1 (PD-1), which is expressed mainly on activated lymphocytes...
September 20, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28843709/pd-l1-in-breast-cancer-comparative-analysis-of-three-different-antibodies
#2
Tejashree Karnik, Bruce F Kimler, Fang Fan, Ossama Tawfik
The Programmed cell death-1 and its ligand-1 (PD-L1) interaction serve as a regulatory check against excessive immune response to antigen and autoimmunity. We compared the performance of three different PD-L1 antibodies (Ventana SP263, Dako 22C3 and BioCare RbMCAL10 antibodies) in 136 invasive ductal carcinoma specimens including 43 primary, 48 locally metastatic and 46 distantly metastatic disease. PD-L1 expression was correlated with clinicopathologic parameters including tumor size, grade, lymphovascular invasion, estrogen receptor (ER), progesterone receptor (PgR), HER2, Ki67, molecular type, TN status...
August 23, 2017: Human Pathology
https://www.readbyqxmd.com/read/28817445/the-safety-of-pembrolizumab-in-metastatic-melanoma-and-rheumatoid-arthritis
#3
Akshjot Puri, Jade Homsi
Immunotherapy has been in use for the treatment of melanoma since a very long time, but only recently have the cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody ipilimumab and programmed cell death-1 inhibitors such as nivolimumab and pembrolizumab been shown to induce marked improvements in survival in patients with metastatic melanoma. An important concern arises in terms of the safety of the use of these agents in patients with autoimmune diseases, solid organ transplant recipients on immunosuppression, patients with a history of previous hepatitis B or C, and patients with HIV infections as these patients were excluded from pivotal immunotherapy studies...
October 2017: Melanoma Research
https://www.readbyqxmd.com/read/28686285/toward-a-structural-understanding-of-nucleic-acid-sensing-toll-like-receptors-in-the-innate-immune-system
#4
REVIEW
Zhikuan Zhang, Umeharu Ohto, Toshiyuki Shimizu
The history of mankind has been plagued by the tug of war with viral infections. Toll-like receptors (TLRs) and other receptors of the innate immune system constitute an early defense system against invading viruses by recognizing the viral genetic material, the nucleic acids (NAs). Agonistic ligands of NA-sensing TLRs play an emerging role in the treatment of viral diseases, demonstrating a crucial role of these receptors. Recently, crystal structures have afforded new insights into TLR recognition of NAs...
October 2017: FEBS Letters
https://www.readbyqxmd.com/read/28603207/varied-immuno-related-adverse-events-induced-by-immune-check-point-inhibitors-nivolumab-associated-psoriasiform-dermatitis-related-with-increased-serum-level-of-interleukin-6
#5
REVIEW
Naoko Okiyama, Ryota Tanaka
  Nivolumab is a standard recombinant antibody treatment for patients with malignant melanoma (MM), which functions as an immune checkpoint inhibitor by blocking the programmed cell death-1 (PD-1) pathway in T cells. However, it leads to various immune-related adverse events (irAEs), and also exacerbates underlying autoimmune diseases. Herein we report cases of MM with irAE. Case 1: A 69-year-old woman with MM developed destructive thyroiditis resulting in hypothyroidism after 3 doses of nivolumab, and had been treated with thyroid gland auxiliary therapy...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28470464/expanding-diversity-and-common-goal-of-regulatory-t-and-b-cells-ii-in-allergy-malignancy-and-transplantation
#6
REVIEW
Grażyna Korczak-Kowalska, Anna Stelmaszczyk-Emmel, Katarzyna Bocian, Ewelina Kiernozek, Nadzieja Drela, Joanna Domagała-Kulawik
Regulation of immune response was found to play an important role in the course of many diseases such as autoimmune diseases, allergy, malignancy, organ transplantation. The studies on immune regulation focus on the role of regulatory cells (Tregs, Bregs, regulatory myeloid cells) in these disorders. The number and function of Tregs may serve as a marker of disease activity. As in allergy, the depletion of Tregs is observed and the results of allergen-specific immunotherapy could be measured by an increase in the population of IL-10(+) regulatory cells...
May 3, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28363334/novel-immune-check-point-inhibiting-antibodies-in-cancer-therapy-opportunities-and-challenges
#7
Yael Diesendruck, Itai Benhar
Drug resistance of tumor cells to chemotherapy is limiting the therapeutic efficacy of most anticancer drugs and represents a major obstacle in medical oncology. However, treatment of various human malignancies with biologics, mostly monoclonal antibodies (mAbs), is not limited by such chemoresistance mechanisms. However, other resistance or evasion mechanisms limit the efficacy to anticancer therapeutic mAbs that engage tumor-associated antigens on the surface of the malignant cells. Immune checkpoint blocking monoclonal antibodies are heralded as a promising therapeutic approach in clinical oncology...
January 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/26524877/the-nafld-index-a-simple-and-accurate-screening-tool-for-the-prediction-of-non-alcoholic-fatty-liver-disease
#8
Naohiro Ichino, Keisuke Osakabe, Keiko Sugimoto, Koji Suzuki, Hiroya Yamada, Hiroji Takai, Hiroko Sugiyama, Jun Yukitake, Takashi Inoue, Koji Ohashi, Tadayoshi Hata, Nobuyuki Hamajima, Toru Nishikawa, Senju Hashimoto, Naoto Kawabe, Kentaro Yoshioka
OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is a common debilitating condition in many industrialized countries that increases the risk of cardiovascular disease. The aim of this study was to derive a simple and accurate screening tool for the prediction of NAFLD in the Japanese population. METHODS: A total of 945 participants, 279 men and 666 women living in Hokkaido, Japan, were enrolled among residents who attended a health check-up program from 2010 to 2014...
January 2015: Rinsho Byori. the Japanese Journal of Clinical Pathology
https://www.readbyqxmd.com/read/26182138/a-case-of-primary-biliary-cirrhosis-and-autoimmune-hepatitis-overlap-showing-acute-presentation-and-transient-seropositivity-for-immunoglobulin-g-and-anti-nuclear-antibody
#9
Keiichi Fujiwara, Katsushi Seza, Yoshihiro Fukuda, Masayuki Nakano, Osamu Yokosuka
Autoimmune hepatitis (AIH) is generally regarded as a clinically and histologically "chronic" hepatitis. It often shows acute presentation like acute hepatitis without typical clinicopathological features of AIH, especially in a case of overlap with primary biliary cirrhosis (PBC). A 52-year-old man showed mild liver dysfunction for the first time at an annual medical check. Two months later, he showed jaundice, and laboratory tests revealed elevation of liver enzymes, hyperbilirubinemia and prolonged prothrombin time activity like acute liver failure...
December 2013: Clinical Journal of Gastroenterology
https://www.readbyqxmd.com/read/25415286/arthritis-and-tenosynovitis-associated-with-the-anti-pd1-antibody-pembrolizumab-in-metastatic-melanoma
#10
Matthew M K Chan, Richard F Kefford, Matteo Carlino, Arthur Clements, Nicholas Manolios
We report the acute onset of polyarticular inflammatory arthritis in 2 patients receiving the immune check-point inhibitor, pembrolizumab (MK-3475), anti-PD1 drug for metastatic melanoma after 14 and 11 months therapy, respectively. The first patient had severe tenosynovitis, synovitis, bone marrow edema, and myositis, whereas the second patient had predominantly synovitis and tenosynovitis. Good symptomatic control was obtained with bisphosphonates and salazopyrin, avoiding the use of T-cell immunosuppressants...
January 2015: Journal of Immunotherapy
https://www.readbyqxmd.com/read/24995908/unconventional-apoptosis-of-polymorphonuclear-neutrophils-pmn-staurosporine-delays-exposure-of-phosphatidylserine-and-prevents-phagocytosis-by-m%C3%AE-2-macrophages-of-pmn
#11
S Franz, L E Muñoz, P Heyder, M Herrmann, M Schiller
Apoptosis of polymorphonuclear neutrophils (PMN) and subsequent 'silent' removal represents an important check-point for the resolution of inflammation. Failure in PMN clearance resulting in secondary necrosis-driven tissue damage has been implicated in conditions of chronic inflammation and autoimmunity. Apoptotic PMN undergo profound biophysical changes that warrant their efficient recognition and uptake by phagocytes before fading to secondary necrosis. In this study, we demonstrate that staurosporine (STS), a non-selective but potent inhibitor of cyclin-dependent kinase and protein kinase C, exerts a drastic impact on PMN apoptosis...
January 2015: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/24674241/stat3-silenced-human-dendritic-cells-have-an-enhanced-ability-to-prime-ifn%C3%AE-production-by-both-%C3%AE-%C3%AE-and-%C3%AE-%C3%AE-t-lymphocytes
#12
Isabella Sanseverino, Cristina Purificato, Barbara Varano, Lucia Conti, Sandra Gessani, M Cristina Gauzzi
Dendritic cells (DC) are an attractive target for therapeutic manipulation of the immune system to enhance insufficient immune responses, such those occurring in cancer, or to dampen dangerous responses in allergic and autoimmune diseases. Main goal of this study was to manipulate human monocyte-derived DC (MDDC) function by silencing STAT3, since this transcription factor plays a key role as a negative regulator of immune surveillance, and is strongly involved in inflammation. STAT3 silencing did not affect the immunophenotype of both immature and toll-like receptor (TLR) ligand-matured DC...
July 2014: Immunobiology
https://www.readbyqxmd.com/read/24558360/egcg-attenuates-autoimmune-arthritis-by-inhibition-of-stat3-and-hif-1%C3%AE-with-th17-treg-control
#13
Eun-Ji Yang, Jennifer Lee, Seon-Young Lee, Eun-Kyung Kim, Young-Mee Moon, Young Ok Jung, Sung-Hwan Park, Mi-La Cho
Epigallocatechin-3-gallate (EGCG) is a green tea polyphenol exerting potent anti-oxidant and anti-inflammatory effects by inhibiting signaling and gene expression. The objective of the study was to evaluate the effect of EGCG on interleukin (IL)-1 receptor antagonist knockout (IL-1RaKO) autoimmune arthritis models. IL-1RaKO arthritis models were injected intraperitoneally with EGCG three times per week after the first immunization. EGCG decreased the arthritis index and showed protective effects against joint destruction in the IL-1RaKO arthritis models...
2014: PloS One
https://www.readbyqxmd.com/read/24504092/selective-accumulation-of-pro-inflammatory-t-cells-in-the-intestine-contributes-to-the-resistance-to-autoimmune-demyelinating-disease
#14
Kerstin Berer, Marina Boziki, Gurumoorthy Krishnamoorthy
Myelin-specific, pro-inflammatory TH17 cells are widely regarded as the drivers of experimental autoimmune encephalomyelitis (EAE), an animal model for Multiple sclerosis (MS). The factors, responsible for the generation and maintenance of TH17 cells as well as their participation in the pathogenic cascade leading to the demyelinating disease, have been studied extensively. However, how these harmful autoreactive cells are controlled in vivo remains unclear. By comparing TCR transgenic mice on a disease susceptible and a disease resistant genetic background, we show here that pathogenic TH17 cells are sequestered within the intestine of spontaneous EAE resistant B10...
2014: PloS One
https://www.readbyqxmd.com/read/24249581/t-bet-is-a-new-synergistic-meeting-point-for-the-bcr-and-tlr9-signaling-cascades
#15
Dorottya Kövesdi, Adrienn Angyal, Krisztina Huber, Dániel Szili, Gabriella Sármay
The importance of the BCR and TLR9 in autoimmunity and in the production of auto-antibodies is well established but the underlying molecular mechanism still needs to be determined. Here, we aim to characterize the BCR-TLR9 cross-talk by its effect on T-bet, as T-bet is activated and regulated by both receptors and has an important role in class-switching to pathological IgG2a in mice. Using primary mouse B cells, we demonstrate that T-bet expression is synergistically elevated by the cross-talk between the BCR and TLR9...
March 2014: European Journal of Immunology
https://www.readbyqxmd.com/read/23497038/amelioration-of-autoimmune-neuroinflammation-by-the-fusion-molecule-fn14%C3%A2-trail
#16
Hodaya Prinz-Hadad, Tehila Mizrachi, Michal Irony-Tur-Sinai, Tatyana B Prigozhina, Alexandra Aronin, Talma Brenner, Michal Dranitzki-Elhalel
BACKGROUND: Multiple sclerosis (MS) is a, T cell-mediated autoimmune disease, the management of which remains challenging. The recently described fusion protein, Fn14·TRAIL, combining the extracellular domain of Fn14 (capable of blocking the pro-inflammatory TWEAK ligand) fused to the extracellular domain of the TRAIL ligand (capable of sending apoptotic signals through its receptors on activated inflammatory cells) was designed to modulate the immune system as an anti-inflammatory agent...
2013: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/23316667/-ctla-4-blockade-a-new-hope-for-the-immunotherapy-of-malignant-melanoma
#17
REVIEW
Michal Lotem, Sharon Merims, Steven Frank, Inna Ospovat, Tamar Peretz
Ipilimumab (Yervoy) is a monocLonal antibody designed to block cytotoxic T cell antigen 4 (CTLA-4), an inhibitory receptor of T lymphocytes. This drug is the first to receive US FDAs approval for advanced stage malignant melanoma in the last 13 years. So far, no survival benefit was achieved for this patient group with single drug or combination chemo- and chemo-immunotherapy. In phase II and III trials, up to 15% of patients had melanoma regressions, with a decreased hazard ratio of death of 0.72 compared to the standard chemotherapy with Dacarbazine...
October 2012: Harefuah
https://www.readbyqxmd.com/read/22394178/b-cell-based-gene-therapy-for-autoimmune-diseases
#18
David W Scott, Ai-Hong Zhang, Yan Su
The essence of the adaptive immune system is self tolerance, which is maintained by various central and peripheral check points. However, the tolerance mechanisms can be broken in autoimmune disease conditions due to genetic predisposition and environmental triggers. As a consequence, a patient's tissue is attacked by his/her own adaptive immune system. An ideal therapy for autoimmune diseases should include methods to re-establish tolerance to the underpinning autoantigen(s). During the last 15 years our lab has been dedicated to developing a novel B-cell gene therapy approach for antigen-specific tolerance induction...
June 2012: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/22132879/translational-mini-review-series-on-b-cell-subsets-in-disease-transitional-b-cells-in-systemic-lupus-erythematosus-and-sj%C3%A3-gren-s-syndrome-clinical-implications-and-effects-of-b-cell-targeted-therapies
#19
REVIEW
A Vossenkämper, P M K Lutalo, J Spencer
Systemic lupus erythematosus (SLE) and Sjögren's syndrome are autoimmune disorders which are characterized by a disturbed B cell homeostasis which leads ultimately to dysfunction of various organs. One of the B cell subsets that appear in abnormal numbers is the population of transitional B cells, which is increased in the blood of patients with SLE and Sjögren's syndrome. Transitional B cells are newly formed B cells. In mice, transitional B cells undergo selection checks for unwanted specificity in the bone marrow and the spleen in order to eliminate autoreactive B cells from the circulating naive B cell population...
January 2012: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/22077831/blockade-of-cytotoxic-t-lymphocyte-antigen-4-as-a-new-therapeutic-approach-for-advanced-melanoma
#20
REVIEW
Xiang-Yang Wang, Daming Zuo, Devanand Sarkar, Paul B Fisher
INTRODUCTION: The incidence of melanoma continues to rise, and prognosis in patients with metastatic melanoma remains poor. The cytotoxic T-lymphocyte antigen-4 (CTLA-4) serves as one of the primary immune check points and downregulates T-cell activation pathways. Enhancing T-cell activation by antibody blockade of CTLA-4 provides a new approach to overcome tumor-induced immune tolerance. Recently, anti-CTLA-4 therapy demonstrated significant clinical benefits in patients with metastatic melanoma, which led to the approval of ipilimumab by the FDA in early 2011...
December 2011: Expert Opinion on Pharmacotherapy
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