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arthritis and CTLA-4

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https://www.readbyqxmd.com/read/29771573/increased-circulating-proinflammatory-t-lymphocytes-in-children-with-different-forms-of-anterior-uveitis-results-from-a-pilot-study
#1
Karoline Walscheid, Lisa Neekamp, Arnd Heiligenhaus, Toni Weinhage, Carsten Heinz, Dirk Foell
PURPOSE: To characterize peripheral blood T cells in juvenile idiopathic arthritis-associated uveitis (JIAU). METHODS: Blood samples were taken from children with JIAU (n = 18), JIA without ocular involvement (n = 11), idiopathic anterior uveitis (IAU, n = 12), and healthy controls (n = 11). Cells were stained for T cell surface markers, and intracellular cytokine staining was performed after cell stimulation and analyzed by flow cytometry. RESULTS: The Th1/Th2 ratio was increased in JIAU patients...
May 17, 2018: Ocular Immunology and Inflammation
https://www.readbyqxmd.com/read/29757670/regulatory-t-cell-dynamics-with-abatacept-treatment-in-rheumatoid-arthritis
#2
Kane Langdon, Nagaraja Haleagrahara
The progressive damage in rheumatoid arthritis (RA) has been linked to an increase in inflammatory Th1/Th17 cells and a decrease in number or function of immunomodulatory regulatory T cells (Tregs). Many therapies that are effective in RA are shown to affect Th1/Th17 cells and/or Tregs. One such therapy, abatacept, utilizes a physiologic immunomodulatory molecule called cytotoxic lymphocyte antigen-4 (CTLA-4) which causes contact-dependent inhibition of inflammatory T-cell activation. Recent advances in CTLA-4 research has uncovered the method by which this occurs physiologically but the actions of the CTLA-4Ig fusion protein are still not fully understood...
May 14, 2018: International Reviews of Immunology
https://www.readbyqxmd.com/read/29610684/immune-toxicity-with-checkpoint-inhibition-for-metastatic-melanoma-case-series-and-clinical-management
#3
Anna J Lomax, Jennifer Lim, Robert Cheng, Arianne Sweeting, Patricia Lowe, Neil McGill, Nicholas Shackel, Elizabeth L Chua, Catriona McNeil
Immune checkpoint inhibitors (anti-PD-1 and anti-CTLA-4 antibodies) are a standard of care for advanced melanoma. Novel toxicities comprise immune-related adverse events (irAE). With increasing use, irAE require recognition, practical management strategies, and multidisciplinary care. We retrospectively evaluated the incidence, kinetics, and management of irAE in 41 patients receiving anti-PD-1 antibody therapy (pembrolizumab) for advanced melanoma. 63% received prior anti-CTLA-4 antibody therapy (ipilimumab)...
2018: Journal of Skin Cancer
https://www.readbyqxmd.com/read/29573850/clinical-presentation-of-immune-checkpoint-inhibitor-induced-inflammatory-arthritis-differs-by-immunotherapy-regimen
#4
Laura C Cappelli, Julie R Brahmer, Patrick M Forde, Dung T Le, Evan J Lipson, Jarushka Naidoo, Lei Zheng, Clifton O Bingham, Ami A Shah
INTRODUCTION: Immune checkpoint inhibitors (ICIs) are a class of cancer immunotherapy, increasingly utilized to treat malignancies. Inflammatory arthritis (IA) is a potential consequence of ICI use, but there is limited information to guide evaluation and management of this immune-related adverse event (irAE). This study aimed to characterize clinical phenotypes, IA treatment and response in the largest cohort of patients with ICI-induced IA reported to date. METHODS: Patients with rheumatologist-confirmed IA occurring during or after ICI treatment with no prior history of autoimmune disease were included...
March 21, 2018: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/29489833/immune-checkpoint-inhibitor-pd-1-pathway-is-down-regulated-in-synovium-at-various-stages-of-rheumatoid-arthritis-disease-progression
#5
Yanxia Guo, Alice M Walsh, Mary Canavan, Mihir D Wechalekar, Suzanne Cole, Xuefeng Yin, Brittney Scott, Mathew Loza, Carl Orr, Trudy McGarry, Michele Bombardieri, Frances Humby, Susanna M Proudman, Costantino Pitzalis, Malcolm D Smith, Joshua R Friedman, Ian Anderson, Loui Madakamutil, Douglas J Veale, Ursula Fearon, Sunil Nagpal
Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development...
2018: PloS One
https://www.readbyqxmd.com/read/29401118/how-does-abatacept-really-work-in-rheumatoid-arthritis
#6
Michael Bonelli, Clemens Scheinecker
PURPOSE OF REVIEW: The purpose of this review is to summarize the current knowledge concerning the mechanisms of action of Abatacept in patients with rheumatoid arthritis. RECENT FINDINGS: Abatacept (CTLA-4Ig) represents a soluble, recombinant, fully humanized fusion protein, comprising the extracellular domain of CTLA-4 and the Fc portion of IgG1. Abatacept binds to the costimulatory molecules CD80 and CD86 on antigen-presenting cells (APC), thereby blocking interaction with CD28 on T cells...
May 2018: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/29370826/bank1-alters-b-cell-responses-and-influences-the-interactions-between-b-cells-and-induced-t-regulatory-cells-in-mice-with-collagen-induced-arthritis
#7
Jie Yang, Jie Ren, Yiming Yang, Juan Sun, Xiaohui Zhou, Shucong Zheng, Dandan Xuan, Yu Xue, Huimin Fan, Jiong Zhang, Hejian Zou, Weiguo Wan, Ning Kong
BACKGROUND: Functional variants of the B cell gene, B cell scaffold protein with ankyrin repeats 1 (BANK1) contribute to rheumatoid arthritis (RA) susceptibility, but their influences on B cell responses are unclear. Moreover, the function of induced T regulatory cells (iTregs) in the inflammatory milieu in a collagen-induced arthritis (CIA) model is unknown. This study was performed to investigate the roles of BANK1 in CIA and the interaction between B cells and iTregs. METHODS: The changes in BANK1 mRNA and protein levels and their correlation with disease severity in CIA were determined...
January 25, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29278210/biologics-in-inflammatory-and-immunomediated-arthritis
#8
Michele M Luchetti, Devis Benfaremo, Armando Gabrielli
BACKGROUND: Biologic drugs, introduced in clinical practice almost twenty years ago, represent nowadays a prominent treatment option in patients with chronic inflammatory arthritis, such as Rheumatoid Arthritis, Psoriatic Arthritis and Spondyloarthritis, that include ankylosing spondylitis and non-radiographic axial spondyloarthritis. METHODS: Several compounds targeting different pathways have been marketed and approved for the treatment of inflammatory arthritis, with a significant impact on the clinical outcomes and the natural history of the diseases...
2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/29230210/checkpoint-blockade-toxicity-and-immune-homeostasis-in-the-gastrointestinal-tract
#9
REVIEW
Michael Dougan
Monoclonal antibodies targeting the regulatory immune "checkpoint" receptors CTLA-4, PD-1, and PD-L1 are now standard therapy for diverse malignancies including melanoma, lung cancer, and renal cell carcinoma. Although effective in many patients and able to induce cures in some, targeting these regulatory pathways has led to a new class of immune-related adverse events. In many respects, these immune toxicities resemble idiopathic autoimmune diseases, such as inflammatory bowel disease, autoimmune hepatitis, rheumatoid arthritis, and vitiligo...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29191375/rheumatologic-symptoms-in-oncologic-patients-on-pd-1-inhibitors
#10
Wilson F Kuswanto, Lindsey A MacFarlane, Lydia Gedmintas, Alexandra Mulloy, Toni K Choueiri, Bonnie L Bermas
OBJECTIVE: Immune checkpoint inhibitors are effective cancer therapies that have been associated with immune-related adverse events (irAEs). Recent reports of irAEs describe symptoms resembling classic rheumatologic syndromes, most notably associated with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor blockade. Though cases have been described, there are fewer reports of rheumatologic disease associated with programmed cell death protein-1 (PD-1) inhibitors. Here, we describe a series of four patients presenting to the Brigham and Women's Hospital (BWH) Arthritis Center with de novo polymyalgia rheumatica (PMR)-type conditions and/or peripheral synovitis after treatment with PD-1/PD-Ligand 1 (PD-L1) pathway inhibitors...
October 31, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/29125905/arthritis-after-cancer-immunotherapy-symptom-duration-and-treatment-response
#11
Melanie H Smith, Anne R Bass
OBJECTIVE: Musculoskeletal manifestations of immune related adverse events (irAEs) after checkpoint inhibitor immunotherapy for cancer remain incompletely characterized and poorly understood. A recently published case series suggested that immunotherapy-induced arthritis is an aggressive process requiring high dose corticosteroids. METHODS: This was a retrospective chart review of all patients with musculoskeletal irAEs first seen by one of the authors between 2014 and 2016...
November 10, 2017: Arthritis Care & Research
https://www.readbyqxmd.com/read/28963072/prostaglandin-e-2-restrains-human-treg-cell-differentiation-via-e-prostanoid-receptor-2-protein-kinase-a-signaling
#12
Hui Li, Hai-Ying Chen, Wen-Xuan Liu, Xian-Xian Jia, Jing-Ge Zhang, Chun-Ling Ma, Xiao-Jing Zhang, Feng Yu, Bin Cong
Regulatory T cells (Treg cells) belong to a class of immunosuppressive cells that control the pathological changes of autoimmunity and inflammation. Prostaglandin E2 (PGE2 ) is a potent lipid mediator of immune inflammation including rheumatoid arthritis (RA) that exerts its effects via four subtypes of G-protein-coupled receptors (EP1-4). The ability of PGE2 to regulate human Treg differentiation has not yet been reported. In the current study, we investigated the effects of PGE2 on the differentiation of naïve T cells from healthy and RA patients into Treg cells and the intracellular signaling involved in this process in vitro...
November 2017: Immunology Letters
https://www.readbyqxmd.com/read/28817445/the-safety-of-pembrolizumab-in-metastatic-melanoma-and-rheumatoid-arthritis
#13
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/28673326/therapeutic-effect-of-a-novel-histone-deacetylase-6-inhibitor-ckd-l-on-collagen-induced-arthritis-in-vivo-and-regulatory-t-cells-in-rheumatoid-arthritis-in-vitro
#14
Bo Ram Oh, Dong-Hyeon Suh, Daekwon Bae, Nina Ha, Young Il Choi, Hyun Jung Yoo, Jin Kyun Park, Eun Young Lee, Eun Bong Lee, Yeong Wook Song
BACKGROUND: Histone deacetylase (HDAC) inhibitor has recently been reported to have a therapeutic effect as an anti-inflammatory agent in collagen-induced arthritis (CIA). We investigated the therapeutic effect of a new selective HDAC6 inhibitor, CKD-L, compared to ITF 2357 or Tubastatin A on CIA and regulatory T (Treg) cells in patients with rheumatoid arthritis (RA). METHODS: CIA was induced by bovine type II collagen (CII) in DBA/1 J mice. Mice were treated with HDAC inhibitor for 18 days...
July 3, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28646772/prevalence-of-immune-related-systemic-adverse-events-in-patients-treated-with-anti-programmed-cell-death-1-anti-programmed-cell-death-ligand-1-agents-a-single-centre-pharmacovigilance-database-analysis
#15
Sébastien Le Burel, Stéphane Champiat, Christine Mateus, Aurélien Marabelle, Jean-Marie Michot, Caroline Robert, Rakiba Belkhir, Jean-Charles Soria, Salim Laghouati, Anne-Laure Voisin, Olivier Fain, Arsène Mékinian, Laetitia Coutte, Tali-Anne Szwebel, Laetitia Dunogeant, Bertrand Lioger, Cécile Luxembourger, Xavier Mariette, Olivier Lambotte
AIM: The growing use of immune checkpoint inhibitors (ICIs) is associated with the occurrence of immune-related adverse events (irAEs). Few data are published on systemic, immunohaematological and rheumatic irAEs. In a pharmacovigilance database analysis, we screened for these irAEs and calculated their prevalence. PATIENTS AND METHODS: Participants were recruited via Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie (REISAMIC)1  a French registry of grade ≥2 irAEs occurring in ICI-treated patients...
September 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28611624/flare-up-of-rheumatoid-arthritis-by-anti-ctla-4-antibody-but-not-by-anti-pd1-therapy-in-a-patient-with-metastatic-melanoma
#16
Nicoletta F Jaberg-Bentele, Michael Kunz, Shatha Abuhammad, Reinhard Dummer
A 47-year-old female patient with rheumatoid arthritis (RA) treated with methotrexate, was diagnosed with metastatic melanoma. After surgical removal of the tumor, the patient started treatment with ipilimumab while methotrexate was stopped. One week after initiation of ipilimumab, the patient developed typical symptoms of RA. Analgetic therapy was started. After 4 cycles of ipilimumab, melanoma progression was radiologically evident. The treatment plan was changed to pembrolizumab (anti-PD1 antibody), and the patient did not show active signs of RA anymore...
January 2017: Case Reports in Dermatology
https://www.readbyqxmd.com/read/28497863/ctla-4-expressed-by-foxp3-regulatory-t-cells-prevents-inflammatory-tissue-attack-and-not-t-cell-priming-in-arthritis
#17
Katrin Klocke, Rikard Holmdahl, Kajsa Wing
Cytotoxic T-lymphocyte antigen 4 (CTLA-4) -mediated regulation of already tolerized autoreactive T cells is critical for understanding autoimmune responses. Although defects in CTLA-4 contribute to abnormal FOXP3+ regulatory T (Treg) cell function in rheumatoid arthritis, its role in autoreactive T cells remains elusive. We studied immunity towards the dominant collagen type II (CII) T-cell epitope in collagen-induced arthritis both in the heterologous setting and in the autologous setting where CII is mutated at position E266D in mouse cartilage...
September 2017: Immunology
https://www.readbyqxmd.com/read/28384040/ctla-4-49-g-a-polymorphism-confers-autoimmune-disease-risk-an-updated-meta-analysis
#18
Ke Wang, Qin Zhu, Yunjie Lu, Hao Lu, Feng Zhang, Xuehao Wang, Ye Fan
BACKGROUND: Cytotoxic T lymphocyte antigen-4 (CTLA-4) plays a pivotal role in immune homeostasis. Dysregulated expression of CTLA-4 leads to many autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes (T1D). There has been a controversial association between the CTLA-4 +49 G/A SNP (rs231775) and autoimmune diseases. Therefore, this meta-analysis was performed to assess the link between rs231775 and autoimmune disease risk. MATERIALS AND METHODS: We retrieved the available studies from PUBMED and EMBASE through February, 2016 and then performed meta-analyses that included all populations, as well as by ethnicity...
April 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28373873/novel-senescent-regulatory-t-cell-subset-with-impaired-suppressive-function-in-rheumatoid-arthritis
#19
Johannes Fessler, Andrea Raicht, Rusmir Husic, Anja Ficjan, Christine Schwarz, Christina Duftner, Wolfgang Schwinger, Winfried B Graninger, Martin H Stradner, Christian Dejaco
OBJECTIVE: Premature senescence of lymphocytes is a hallmark of inflammatory rheumatic diseases such as rheumatoid arthritis (RA). Early T-cell aging affects conventional T-cells but is presumably not limited to this cell population; rather it might also occur in the regulatory T-cells (Tregs) compartment. In RA, Tregs fail to halt aberrant immune reactions and disease progression. Whether this is associated with early Treg senescence leading to phenotypic and functional changes of this subset is elusive so far...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28325750/molecular-pathways-evaluating-the-potential-for-b7-h4-as-an-immunoregulatory-target
#20
REVIEW
Heather L MacGregor, Pamela S Ohashi
With the clinical success of CTLA-4 and PD-1 blockade in treating malignancies, there is tremendous interest in finding new ways to augment antitumor responses by targeting other inhibitory molecules. In this review, we describe one such molecule. B7-H4, a member of the B7 family of immunoregulatory proteins, inhibits T cell proliferation and cytokine production through ligation of an unknown receptor expressed by activated T cells. Notably, B7-H4 protein expression is observed in a high proportion of patients' tumors across a wide variety of malignancies...
June 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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