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Clinical Immunology: the Official Journal of the Clinical Immunology Society

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https://www.readbyqxmd.com/read/29689313/alpha-lactose-reverses-liver-injury-via-blockade-of-tim-3-mediated-cd8-apoptosis-in-sepsis
#1
Zhengping Wei, Pingfei Li, Yao Yao, Hai Deng, Shengwu Yi, Cong Zhang, Han Wu, Xiuxiu Xie, Minghui Xia, Ran He, Xiang-Ping Yang, Zhao-Hui Tang
In sepsis, the liver plays a crucial role in regulating immune responses and is also a target organ for immune-related injury. Despite the critical function of CD8+ T cells against opportunistic viral infections, the CD8 immune response in the liver during sepsis remains elusive. Here we found that Tim-3 is highly up-regulated in liver CD8+ T cells in a mouse cecal ligation and puncture model and in peripheral blood CD8+ T cells of human patients with sepsis. The expression of Tim-3 in liver CD8+ T cells displayed a bi-phasic pattern and deletion of Tim-3 led to reduction of CD8+ T cell apoptosis...
April 21, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29679709/unique-glandular-ex-vivo-th1-and-th17-receptor-motifs-in-sj%C3%A3-gren-s-syndrome-patients-using-single-cell-analysis
#2
Alexandria Voigt, Katherine Bohn, Sukesh Sukumaran, Carol M Stewart, Indraneel Bhattacharya, Cuong Q Nguyen
Primary Sjögren's syndrome (pSS) is an autoimmune disease in which the underlying cause has yet to be elucidated. The main objective of this study was to determine the T cell receptor (TCR) repertoires of individual infiltrating T helper (Th)-1 and 17 cells of pSS patients using single-cell analysis. Single-cell analysis of ex-vivo infiltrating T cells demonstrated that pSS patients had higher frequencies of activated Th17 cells. Single-cell TCR sequencing revealed that TCRβ variable (TRBV)3-1/joint (J)1-2 (CLFLSMSACVW) and TRBV20-1/J1-1 (SVGSTAIPP*T) were expressed by activated Th1 and Th17 cells in both cohorts...
April 18, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29678503/caffeine-inhibits-stat1-signaling-and-downregulates-inflammatory-pathways-involved-in-autoimmunity
#3
Merve Iris, Pei-Suen Tsou, Amr H Sawalha
Caffeine is a widely consumed pharmacologically active product. We focused on characterizing immunomodulatory effects of caffeine on peripheral blood mononuclear cells. Caffeine at high doses showed a robust downregulatory effect on cytokine activity and genes related to several autoimmune diseases including lupus and rheumatoid arthritis. Dose-dependent validation experiments showed downregulation at the mRNA levels of key inflammatory genes including STAT1, TNF, and PPARG. TNF and PPARG were suppressed even with the lowest caffeine dose tested, which corresponds to the serum concentration of caffeine after administration of one cup of coffee...
April 17, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29673902/la-ssb-chimeric-autoantibody-receptor-modified-nk92mi-cells-for-targeted-therapy-of-autoimmune-disease
#4
Huimin Meng, Xue Sun, Yanhui Song, Jianxuan Zou, Gangli An, Zeming Jin, Lin Yang
It has been long sought to specifically eliminate B-cell clones that generate autoreactive antibodies, while sparing the immune system when combating autoimmune disease. Although it was impossible to achieve this goal before, newly developed techniques have made it feasible today. Autoantibodies against La/SSB were involved in several autoimmune diseases. Here, we aimed to introduce La/SSB epitope-based chimeric autoantibody receptors (CAAR) into NK92MI cells enabled it to destroy the corresponding La/SSB-specific B cell receptor (BCR) -bearing lymphoma cells (LaA-BCR-Romas, LaA-BCR-Maver-1, and LaA-BCR-Jurkat cells)...
April 16, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29673901/the-role-of-syk-in-peripheral-t-cells
#5
Jeoung-Eun Park, Sirshendu Majumdar, David D Brand, Edward F Rosloniec, Ae-Kyung Yi, John M Stuart, Andrew H Kang, Linda K Myers
The aim of this study was to understand how Syk affects peripheral T cell function. T cells from Syk-/- chimeric mice and DR1 Sykfl/fl CD4cre conditional mice gave strong CD3-induced Th1, Th2, and Th17 cytokine responses. However, an altered peptide ligand (APL) of human CII (256-276) with two substitutions (F263N, E266D), also called A12, elicited only Th2 cytokine responses from Sykfl/fl T cells but not Sykfl/fl- CD4cre T cells. Western blots revealed a marked increase in the phosphorylation of Syk, JNK and p38 upon A12/DR1 activation in WT or Sykfl/fl T cells but not in Sykfl/fl CD4-cre cells...
April 16, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29654845/immune-senescence-epigenetics-and-autoimmunity
#6
Donna Ray, Raymond Yung
Aging of the immune system in humans and animals is characterized by a decline in both adaptive and innate immune responses. Paradoxically, aging is also associated with a state of chronic inflammation ("inflammaging") and an increased likelihood of developing autoimmune diseases. Epigenetic changes in non-dividing and dividing cells, including immune cells, due to environmental factors contribute to the inflammation and autoimmunity that characterize both the state and diseases of aging. Here, we review the epigenetic mechanisms involved in the development of immune senescence and autoimmunity in old age...
April 11, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29654844/oxidative-stress-and-dietary-micronutrient-deficiencies-contribute-to-overexpression-of-epigenetically-regulated-genes-by-lupus-t-cells
#7
Donna Ray, Faith M Strickland, Bruce C Richardson
Patients with active lupus have altered T cells characterized by low DNA methyltransferase levels. We hypothesized that low DNA methyltransferase levels synergize with low methionine levels to cause greater overexpression of genes normally suppressed by DNA methylation. CD4+ T cells from lupus patients and controls were stimulated with PHA then cultured in custom media with normal or low methionine levels. Oxidative stress was induced by treating the normal CD4+ T cells with peroxynitrite prior to culture. Methylation sensitive gene expression was measured by flow cytometry...
April 11, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29649576/epigenetic-alterations-in-primary-sj%C3%A3-gren-s-syndrome-an-overview
#8
Juliana Imgenberg-Kreuz, Johanna K Sandling, Gunnel Nordmark
Primary Sjögren's syndrome (pSS) is a chronic autoimmune rheumatic disease characterized by inflammation of exocrine glands, mainly salivary and lacrimal glands. In addition, pSS may affect multiple other organs resulting in systemic manifestations. Although the precise etiology of pSS remains elusive, pSS is considered to be a multi-factorial disease, where underlying genetic predisposition, environmental factors and epigenetic mechanisms contribute to disease development. Epigenetic mechanisms, such as DNA methylation, histone modifications and non-coding RNAs, may constitute a dynamic link between genome, environment and phenotypic manifestation by their modulating effects on gene expression...
April 9, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29649575/the-interaction-between-environmental-triggers-and-epigenetics-in-autoimmunity
#9
Bruce Richardson
Systemic lupus erythematosus flares when genetically predisposed people encounter environmental agents that cause oxidative stress, such as infections and sunlight. How these modify the immune system to initiate flares is unclear. Drug induced lupus models demonstrate that CD4+ T cells epigenetically altered with DNA methylation inhibitors cause lupus in animal models, and similar T cells are found in patients with active lupus. How infections and sun exposure inhibit T cell DNA methylation is unclear. DNA methylation patterns are replicated each time a cell divides in a process that requires DNA methyltransferase one (Dnmt1), which is upregulated as cells enter mitosis, as well as the methyl donor S-adenosylmethionine, created from dietary sources...
April 9, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29631029/elevated-expression-of-tslp-and-il-33-in-beh%C3%A3-et-s-disease-skin-lesions-il-37-alleviate-inflammatory-effect-of-tslp
#10
Olfa Kacem, Wajih Kaabachi, Imen Ben Dhifallah, Agnes Hamzaoui, Kamel Hamzaoui
The release of TSLP and IL-33 affect the skin integrity, which unsettled transcription factor regulators. We investigate TSLP and IL-33 in Behçet disease (BD) and we prove the effect of the anti-inflammatory cytokine IL-37 in BD skin lesions on TSLP production. TSLP, IL-33 and GATA-3/T-bet, were measured using PCR in BD skin lesions. We tested the suppressive effect of IL-37 on skin samples stimulated with a cytokine mixture inducing TSLP expression. TSLP and IL-33 were increased in BD patients particularly in patients having skin manifestations and correlate with indexed skin lesions...
April 6, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29621613/cytokine-targeting-in-rheumatoid-arthritis
#11
Viet L Bui, Ernie Brahn
No abstract text is available yet for this article.
April 2, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29614335/comparison-of-efficacy-of-tnf-inhibitors-and-abatacept-in-patients-with-rheumatoid-arthritis-adjusted-with-propensity-score-matching
#12
Satoshi Kubo, Shingo Nakayamada, Kazuhisa Nakano, Norifumi Sawamukai, Shintaro Hirata, Kentaro Hanami, Kazuyoshi Saito, Yoshiya Tanaka
The aim of this study was to compare the clinical outcome of patients with rheumatoid arthritis seen in routine clinical practice treated with either TNF inhibitors or abatacept. To overcome potential bias, both propensity score matching and Inverse Probability of Treatment Weighting were used for patient selection. The propensity score matching procedure selected 315 matched pairs of patients who were treated with TNF inhibitors or abatacept. At week 52, SDAI in TNF inhibitors was lower than abatacept. In contrast, analysis of biologics-naive patients using the propensity-score matching (n = 150; in each group) showed comparable clinical efficacy...
March 31, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29608971/more-intensive-cmv-infection-in-chronic-heart-failure-patients-contributes-to-higher-t-lymphocyte-differentiation-degree
#13
Marco Antonio Moro-García, Fernando López-Iglesias, Raquel Marcos-Fernández, Eva Bueno-García, Beatriz Díaz-Molina, José Luis Lambert, Francisco Manuel Suárez-García, Cesar Morís de la Tassa, Rebeca Alonso-Arias
Immunosenescence in chronic heart failure (CHF) is characterized by a high frequency of differentiated T-lymphocytes, contributing to an inflammatory status and a deficient ability to generate immunocompetent responses. CMV is the best known inducer of T-lymphocyte differentiation, and is associated with the phenomenon of immunosenescence. In this study, we included 58 elderly chronic heart failure patients (ECHF), 60 healthy elderly controls (HEC), 40 young chronic heart failure patients (YCHF) and 40 healthy young controls (HYC)...
March 30, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29608970/characterization-of-vibrio-cholerae-neuraminidase-as-an-immunomodulator-for-novel-formulation-of-oral-allergy-immunotherapy
#14
Susanne C Diesner, Cornelia Bergmayr, Xue-Yan Wang, Denise Heiden, Sarah Exenberger, Franziska Roth-Walter, Philipp Starkl, Davide Ret, Isabella Pali-Schöll, Franz Gabor, Eva Untersmayr
To improve current mucosal allergen immunotherapy Vibrio cholerae neuraminidase (NA) was evaluated as a novel epithelial targeting molecule for functionalization of allergen-loaded, poly(D,L-lactide-co-glycolide) (PLGA) microparticles (MPs) and compared to the previously described epithelial targeting lectins wheat germ agglutinin (WGA) and Aleuria aurantia lectin (AAL). All targeters revealed binding to Caco-2 cells, but only NA had high binding specificity to α-L fucose and monosialoganglioside-1. An increased transepithelial uptake was found for NA-MPs in a M-cell co-culture model...
March 30, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29605707/epigenome-wide-association-studies-for-systemic-autoimmune-diseases-the-road-behind-and-the-road-ahead
#15
Elena Carnero-Montoro, Marta E Alarcón-Riquelme
Epigenetics is known to be an important mechanism in the pathogenesis of autoimmune diseases. Epigenetic variations can act as integrators of environmental and genetic exposures and propagate activated states in immune cells. Studying epigenetic alterations by means of genome-wide approaches promises to unravel novel molecular mechanisms related to disease etiology, disease progression, clinical manifestations and treatment responses. This paper reviews what we have learned in the last five years from epigenome-wide studies for three systemic autoimmune diseases, namely systemic lupus erythematosus, primary Sjögren's syndrome, and rheumatoid arthritis...
March 29, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29601854/patients-with-core-antibody-positive-and-surface-antigen-negative-hepatitis-b-anti-hbc-hbsag-on-anti-tnf-therapy-have-a-low-rate-of-reactivation
#16
William T Clarke, Shreya S Amin, Konstantinos Papamichael, Joseph D Feuerstein, Adam S Cheifetz
Anti-TNF agents are widely used to treat immune-mediated disorders. Reactivation of Hepatitis B virus (HBV) is associated with immunosuppressive agents and biologics such as anti-TNF. There are limited data and differing guidelines for patients with negative hepatitis B surface antigen (HBsAg-) but positive antibody to hepatitis B core antigen (anti-HBc+) on anti-TNF with regards to outcomes and need for anti-viral prophylaxis. We examined the prevalence of HBV reactivation in a single-center retrospective cohort study of 120 HBsAg-, anti-HBc+ patients on anti-TNF, totaling 346...
March 27, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29596912/characterization-of-a-large-unc13d-gene-duplication-in-a-patient-with-familial-hemophagocytic-lymphohistiocytosis-type-3
#17
Eitaro Hiejima, Hirofumi Shibata, Takahiro Yasumi, Saeko Shimodera, Masayuki Hori, Kazushi Izawa, Tomoki Kawai, Masaki Matsuoka, Yasuko Kojima, Akira Ohara, Ryuta Nishikomori, Osamu Ohara, Toshio Heike
Familial hemophagocytic lymphohistiocytosis (FHL) type 3 is a life-threatening immune dysregulation syndrome caused by mutations in the UNC13D gene, encoding the munc13-4 protein, which is important for function of cytotoxic lymphocytes. FHL3 accounts for 30-40% of FHL cases, and more than 100 mutations in the UNC13D gene have been described to date. We describe the first case of FHL3 carrying an intragenic duplication of UNC13D, apparently mediated by recombination of Alu elements. NK cell degranulation and munc13-4 protein expression assays are useful for early identification of such mutations, which may be missed by analysis of genomic DNA alone...
March 26, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29574040/epigenetics-as-biomarkers-in-autoimmune-diseases
#18
Haijing Wu, Jieyue Liao, Qianwen Li, Ming Yang, Ming Zhao, Qianjin Lu
Autoimmune diseases are immune system disorders in which immune cells cannot distinguish self-antigens from foreign ones. The current criteria for autoimmune disease diagnosis are based on clinical manifestations and laboratory tests. However, none of these markers shows both high sensitivity and specificity. In addition, some autoimmune diseases, for example, systemic lupus erythematosus (SLE), are highly heterogeneous and often exhibit various manifestations. On the other hand, certain autoimmune diseases, such as Sjogren's syndrome versus SLE, share similar symptoms and autoantibodies, which also causes difficulties in diagnosis...
March 21, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29574039/phase-ib-trial-of-folate-binding-protein-fbp-derived-peptide-vaccines-e39-and-an-attenuated-version-e39-an-analysis-of-safety-and-immune-response
#19
Timothy J Vreeland, Jennifer K Litton, Na Qiao, Anne V Philips, Gheath Alatrash, Diane F Hale, Doreen O Jackson, Kaitlin M Peace, Julia M Greene, John S Berry, Guy T Clifton, George E Peoples, Elizabeth A Mittendorf
In this randomized phase Ib trial, we tested combining the E39 peptide vaccine with a vaccine created from E39', an attenuated version of E39. Patients with breast or ovarian cancer, who were disease-free after standard of care therapy, were enrolled and randomized to one of three arms. Arm EE received six E39 inoculations; arm EE' received three E39 inoculations followed by three E39'; and arm E'E received three E39' inoculations, followed by three E39. Within each arm, the first five patients received 500 μg of peptide and the remainder received 1000 μg...
March 21, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29572183/tnfaip3-haploinsufficiency-is-the-cause-of-autoinflammatory-manifestations-in-a-patient-with-a-deletion-of-13mb-on-chromosome-6
#20
Clara Franco-Jarava, Hongying Wang, Andrea Martin-Nalda, de la Sierra Daniel Alvarez, Marina García-Prat, Domingo Bodet, Vicenç García-Patos, Alberto Plaja, Francesc Rudilla, Victor Rodriguez-Sureda, Laura García-Latorre, Ivona Aksentijevich, Roger Colobran, Pere Soler-Palacín
There is scarce literature about autoinflammation in syndromic patients. We describe a patient who, in addition to psychomotor and growth delay, presented with fevers, neutrophilic dermatosis, and recurrent orogenital ulcers. Comparative Genomic Hybridization (CGH) array permitted to identify a 13.13Mb deletion on chromosome 6, encompassing 53 genes, and including TNFAIP3 gene (A20). A20 is a potent inhibitor of the NF-kB signalling pathway and restricts inflammation via its deubiquitinase activity. Western blotting and immunoprecipitation assays showed decreased A20 expression and increased phosphorylation of p65 and IkBa...
March 20, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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