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Clinical Immunology: the Official Journal of the Clinical Immunology Society

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https://www.readbyqxmd.com/read/27923702/nfkb1-regulates-human-nk-cell-maturation-and-effector-functions
#1
Vassilios Lougaris, Ornella Patrizi, Manuela Baronio, Giovanna Tabellini, Giacomo Tampella, Eufemia Damiati, Natalie Frede, Jos W M van der Meer, Manfred Fliegauf, Bodo Grimbacher, Silvia Parolini, Alessandro Plebani
NFKB1, a component of the canonical NF-κB pathway, was recently reported to be mutated in a limited number of CVID patients. CVID-associated mutations in NFKB2 (non-canonical pathway) have previously been shown to impair NK cell cytotoxic activity. Although a biological function of NFKB1 in non-human NK cells has been reported, the role of NFKB1 mutations for human NK cell biology and disease has not been investigated yet. We decided therefore to evaluate the role of monoallelic NFKB1 mutations in human NK cell maturation and functions...
December 3, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27923701/prognostic-significance-of-repeat-biopsy-in-lupus-nephritis-histopathologic-worsening-and-a-short-time-between-biopsies-is-associated-with-significantly-increased-risk-for-end-stage-renal-disease-and-death
#2
Cristina Arriens, Sixia Chen, David R Karp, Ramesh Saxena, Kamalanathan Sambandam, Eliza Chakravarty, Judith A James, Joan T Merrill
BACKGROUND/PURPOSE: Approximately half of patients with systemic lupus erythematosus (SLE) develop lupus nephritis (LN), a major cause of morbidity and early mortality in that disease. Prolonged renal inflammation is associated with irreversible kidney damage which confers a 30% risk of end stage renal disease (ESRD), making early, aggressive treatment mandatory. Failure to achieve therapeutic response or recurrence of renal flare often prompts repeat biopsy. However, the role of repeat biopsy in determining long-term renal prognosis remains controversial...
December 3, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27919819/patterns-of-constitutively-phosphorylated-kinases-in-b-cells-are-associated-with-disease-severity-in-common-variable-immunodeficiency
#3
Eli Taraldsrud, Pål Aukrust, Silje Jørgensen, Ole Christian Lingjærde, Johanna Olweus, June H Myklebust, Børre Fevang
Patients with common variable immunodeficiency (CVID) constitute a clinically and immunologically heterogeneous group characterized by B-cell dysfunction with hypogammaglobulinemia and defective immunoglobulin class switch of unknown etiology. Current classification systems are insufficient to achieve precise disease management. Characterization of signaling pathways essential for B-cell differentiation and class switch could provide new means to stratify patients. We evaluated constitutive and induced signaling by phospho-specific flow cytometry in 26 CVID patients and 18 healthy blood donors...
December 2, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27916705/newborn-screening-for-severe-combined-immunodeficiency-using-a-novel-and-simplified-method-to-measure-t-cell-excision-circles-trec
#4
Laura Tagliaferri, Joachim B Kunz, Margit Happich, Susanna Esposito, Thomas Bruckner, Daniel Hübschmann, Jürgen G Okun, Georg F Hoffmann, Ansgar Schulz, Judit Kappe, Carsten Speckmann, Martina U Muckenthaler, Andreas E Kulozik
The prognosis of children with severe combined immunodeficiency (SCID) depends on a presymptomatic diagnosis and early treatment before complications occur. We established and tested a simplified, practical and economic newborn screening method based on the quantification of T-cell receptor excision circles (TRECs) on dried blood spots (DBSs) through qPCR. Our method was validated by the analysis of 11 positive controls, which all showed an absence of TRECs, thus yielding a sensitivity of 100%. Further, we analyzed 6034 anonymized newborns of whom 6031 (99,95%) showed a normal TREC qPCR with a median of 600 estimated TREC copies/1...
December 1, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27915003/abnormal-cell-clearance-and-accumulation-of-autophagic-vesicles-in-lymphocytes-from-patients-affected-with-ataxia-teleangiectasia
#5
Roberta D'Assante, Anna Fusco, Loredana Palamaro, Elena Polishchuk, Roman Polishchuk, Gabriella Bianchino, Vitina Grieco, Maria Rosaria Prencipe, Andrea Ballabio, Claudio Pignata
Ataxia-Teleangiectasia (A-T) is a neurodegenerative disorder due to mutations in ATM gene. ATM in the nucleus ensures DNA repair, while its role in the cytosol is still poorly clarified. Abnormal autophagy has been documented in other neurodegenerative disorders, thus we evaluated whether alteration in this process may be involved in the pathogenesis of A-T by analyzing the autophagic vesicles and the genes implicated in the different stages of autophagy. Through transmission electron microscopy (TEM) and immunofluorescence analysis we observed an accumulation of APs associated with a LC3 puncta pattern, and a reduced number of ALs...
November 30, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27894980/natural-killer-cells-in-inflammatory-heart-disease
#6
REVIEW
SuFey Ong, Noel R Rose, Daniela Čiháková
Despite of a multitude of excellent studies, the regulatory role of natural killer (NK) cells in the pathogenesis of inflammatory cardiac disease is greatly underappreciated. Clinical abnormalities in the numbers and functions of NK cells are observed in myocarditis and inflammatory dilated cardiomyopathy (DCMi) as well as in cardiac transplant rejection [1-6]. Because treatment of these disorders remains largely symptomatic in nature, patients have little options for targeted therapies [7,8]. However, blockade of NK cells and their receptors can protect against inflammation and damage in animal models of cardiac injury and inflammation...
November 25, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27890707/novel-mutation-in-dock8-hies-with-severe-phenotype-and-successful-transplantation
#7
Latifa Al Shekaili, Farrukh Sheikh, Sulaiman Al Gazlan, Hasan Al Dhekri, Hamoud Al Mousa, Abdulaziz Al Ghonaium, Bander Al Saud, Saleh Al Mohsen, Agha M Rehan Khaliq, Safiah Al Sumayli, Mufarreh Al Zahrani, Anas Dababo, Ammar AlKawi, Abbas Hawwari, Rand Arnaout
BACKGROUND: Hyper-IgE syndrome (HIES) due to DOCK8 deficiency is an autosomal recessive (AR) primary combined immunodeficiency which results in significant morbidity and mortality at a young age. Different mutations in the DOCK8 gene can lead to variable severity of the disease. OBJECTIVE: We evaluated the genetic mutations in three related patients with severe clinical manifestations suggestive of AR HIES. We also explored whether treatment with stem cell transplantation could lead to complete disease resolution...
November 23, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27890706/the-sphingosine-1-phosphate-receptor-a-novel-therapeutic-target-for-multiple-sclerosis-and-other-autoimmune-diseases
#8
REVIEW
Yang Mao-Draayer, Jeffrey Sarazin, David Fox, Elena Schiopu
Multiple sclerosis (MS) is a prototype autoimmune disease of the central nervous system (CNS). Currently, there is no drug that provides a cure for MS. To date, all immunotherapeutic drugs target relapsing remitting MS (RR-MS); it remains a daunting medical challenge in MS to develop therapy for secondary progressive MS (SP-MS). Since the approval of the non-selective sphingosine-1-phosphate (S1P) receptor modulator FTY720 (fingolimod [Gilenya®]) for RR-MS in 2010, there have been many emerging studies with various selective S1P receptor modulators in other autoimmune conditions...
November 23, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27876461/neutrophil-infiltration-mediated-by-cxcl5-accumulation-in-the-laryngeal-squamous-cell-carcinoma-microenvironment-a-mechanism-by-which-tumour-cells-escape-immune-surveillance
#9
Duo Zhang, Jian Zhou, Di Tang, Lin Zhou, Liang Chou, Kuang-Yen Chou, Lei Tao, Li-Ming Lu
The CXCL5 chemokine is important for neutrophil accumulation in tumour tissues. In this report, we attempted to clarify whether and how infiltrating tumour-associated neutrophils (TANs) in laryngeal squamous cell carcinoma (LSCC) affect the proliferation and activation of T cells. We examined chemokine expression by real-time PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) and performed an immunohistochemical analysis of LSCC microarrays. The relationship between CXCL5 and CD66b (a neutrophil marker) was investigated by immunofluorescence staining...
November 19, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27876460/imo-8400-a-toll-like-receptor-7-8-and-9-antagonist-demonstrates-clinical-activity-in-a-phase-2a-randomized-placebo-controlled-trial-in-patients-with-moderate-to-severe-plaque-psoriasis
#10
Deepak M W Balak, Martijn B A van Doorn, Robert D Arbeit, Rianne Rijneveld, Erica Klaassen, Tim Sullivan, Julie Brevard, H Bing Thio, Errol P Prens, J Koos Burggraaf, Robert Rissmann
BACKGROUND: Aberrant toll-like receptors (TLRs) 7, 8, and 9 activation by self-nucleic acids is implicated in immune-mediated inflammatory diseases (IMIDs) such as psoriasis. In preclinical IMID models, blocking TLR-activation reduced disease severity. IMO-8400 is a first-in-class, oligonucleotide-based antagonist of TLRs 7, 8, and 9. We evaluated the short-term safety and proof-of-concept for efficacy of IMO-8400 in a first-in-patient phase 2 trial. METHODS: Forty-six psoriasis patients were randomly assigned to IMO-8400 in four dose levels or placebo for 12weeks...
November 19, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27871915/inhibition-of-siglec-1-by-lentivirus-mediated-small-interfering-rna-attenuates-atherogenesis-in-apoe-deficient-mice
#11
Yi-Song Xiong, Ai-Lin Wu, Dong Mu, Juan Yu, Ping Zeng, Yi Sun, Jie Xiong
BACKGROUND: Siglec-1 is highly expressed on circulating monocytes and plaque macrophages in atherosclerotic patients, but the exact role of Siglec-1 in atherosclerosis has not been elucidated. METHODS: Lentiviral vector containing small interfering RNA targeting Siglec-1 (Lv-shSiglec-1) or control vector (Lv-shNC) were injected intravenously into 6-week old Apoe(-/-) mice. Then onset of atherosclerosis was observed. RESULTS: Siglec-1 was highly expressed in aortic plaques and it can be down-regulated by Lv-shSiglec-1 injection...
November 15, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27871914/neonatal-levels-of-adiponectin-interleukin-10-and-interleukin-12-are-associated-with-the-risk-of-developing-type-1-diabetes-in-childhood-and-adolescence-a-nationwide-danish-case-control-study
#12
Steffen U Thorsen, Christian B Pipper, Stefanie Eising, Kristin Skogstrand, David M Hougaard, Jannet Svensson, Flemming Pociot
BACKGROUND/AIM: An in-depth understanding of the early phase of type 1 diabetes (T1D) pathogenesis is important for targeting primary prevention. We examined if 14 preselected mediators of immune responses differed in neonates that later developed T1D compared to control neonates. METHODS: The study is a case-control study with a 1:2 matching. The individuals were born between 1981 through 2002. Cases were validated using the National Patient Register and the Danish Childhood Diabetes Register...
November 15, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27871892/pso-p27-a-serpinb3-b4-derived-protein-is-most-likely-a-common-autoantigen-in-chronic-inflammatory-diseases
#13
Ole-Jan Iversen, Hilde Lysvand, Geir Slupphaug
Autoimmune diseases are characterized by chronic inflammatory reactions localized to an organ or organ-system. They are caused by loss of immunologic tolerance toward self-antigens, causing formation of autoantibodies that mistakenly attack their own body. Psoriasis is a chronic inflammatory autoimmune skin disease in which the underlying molecular mechanisms remain elusive. In this review, we present evidence accumulated through more than three decades that the serpin-derived protein Pso p27 is an autoantigen in psoriasis and probably also in other chronic inflammatory diseases...
November 15, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27856306/enhanced-formation-of-giant-cells-in-common-variable-immunodeficiency-relation-to-granulomatous-disease
#14
Timothy H Scott-Taylor, Karen Whiting, Ruth Pettengell, David A Webster
Peripheral monocytes from patients with common variable immunodeficiency (CVID) had on average a 2 fold greater tendency to form giant cells in medium without additional cytokines. Giant cell formation was faster and 3 to 5 fold higher in most CVID cells compared to normal. Addition of IL4, GMCSF, IFNγ, TNFa and both T cell and monocyte conditioned media promoted monocyte fusion of some CVID individuals over 5 fold the normal average level, with combinations of cytokines and monokines acting synergistically...
November 14, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27856305/cyr61-ccn1-is-involved-in-the-pathogenesis-of-psoriasis-vulgaris-via-promoting-il-8-production-by-keratinocytes-in-a-jnk-nf-%C3%AE%C2%BAb-pathway
#15
Pinru Wu, Gang Ma, Xianjin Zhu, Ting Gu, Jie Zhang, Yue Sun, Hui Xu, Rongfen Huo, Beiqing Wang, Baihua Shen, Xiangdong Chen, Ningli Li
PURPOSE: Interleukin-8 (IL-8) is an important factor in the pathogenesis of psoriasis vulgaris, which is characterized by proliferation of keratinocytes, neutrophil infiltration and angiogenesis. Cysteine-rich 61 (Cyr61/CCN1), a secreted extracellular matrix protein, is a novel proinflammatory factor. Whether Cyr61 is involved in the development of psoriasis vulgaris via IL-8 production remains unknown. In this study we explore the role of Cyr61 in IL-8 expression regulation in vivo and in vitro...
November 14, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27856304/a-heterozygous-dominant-negative-mutation-in-the-coiled-coil-domain-of-stat1-is-the-cause-of-autosomal-dominant-mendelian-susceptibility-to-mycobacterial-diseases
#16
Masahiro Ueki, Masafumi Yamada, Kenta Ito, Yusuke Tozawa, Saeko Morino, Yuho Horikoshi, Hidetoshi Takada, Shimaa Said Mohamed Ali Abdrabou, Shunichiro Takezaki, Ichiro Kobayashi, Tadashi Ariga
Heterozygous dominant-negative mutations of STAT1 are responsible for autosomal-dominant Mendelian susceptibility to mycobacterial diseases (AD-MSMD). So far, only 7 mutations have been previously described and are localized to 3 domains: the DNA-binding domain, the SH2 domain, and the tail segment. In this study, we demonstrated the first coiled-coil domain (CCD) mutation of c.749G>C, p.G250A (G250A) in STAT1 as a genetic cause of AD-MSMD in a patient with mycobacterial multiple osteomyelitis. This de novo heterozygous mutation was shown to have a dominant-negative effect on the gamma-activated sequence (GAS) transcriptional activity following IFN-γ stimulation, which could be attributable to the abolished phosphorylation of STAT1 from the wild-type (WT) allele...
November 14, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27847316/allergies-a-t-cells-perspective-in-the-era-beyond-the-th1-th2-paradigm
#17
REVIEW
Moritz Berker, Larissa Johanna Frank, Anja Lidwina Geßner, Niklas Grassl, Anne Verena Holtermann, Stefanie Höppner, Christian Kraef, Martin Dominik Leclaire, Pia Maier, David Alexander Christian Messerer, Lino Möhrmann, Jan Philipp Nieke, Diana Schoch, Dominik Soll, Christina Marianne Paulina Woopen
Allergic diseases have emerged as a major health care burden, especially in the western hemisphere. They are defined by overshooting reactions of an aberrant immune system to harmless exogenous stimuli. The TH1/TH2 paradigm assumes that a dominance of TH2 cell activation and an inadequate TH1 cell response are responsible for the development of allergies. However, the characterization of additional T helper cell subpopulations such as TH9, TH17, TH22, THGM-CSF and their interplay with regulatory T cells suggest further layers of complexity...
November 12, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27825976/progressive-severe-b-cell-deficiency-in-pediatric-rubinstein-taybi-syndrome
#18
LETTER
Vassilios Lougaris, Elena Facchini, Manuela Baronio, Tiziana Lorenzini, Daniele Moratto, Fernando Specchia, Alessandro Plebani
No abstract text is available yet for this article.
November 5, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27818202/the-expression-of-bcl-6-in-circulating-follicular-helper-like-t-cells-positively-correlates-with-the-disease-activity-in-systemic-lupus-erythematosus
#19
Xin Huang, Haijing Wu, Hong Qiu, Huilan Yang, Yaxiong Deng, Ming Zhao, Hairong Luo, Xiang Zhou, Yubin Xie, Vera Chan, Chak-Sing Lau, Qianjin Lu
Increased circulating follicular helper-like T cells (cTfh) are reported in systemic lupus erythematosus (SLE) patients. However, whether B-cell lymphoma 6 (Bcl-6) is expressed in cTfh cells remains to be clarified. In this study, we found that the frequencies of CD4(+)CXCR5(hi)PD-1(hi)cTfh, CD4(+)CXCR5(hi)PD-1(hi)ICOS(hi), and CD4(+)CXCR5(hi)PD-1(hi)Bcl-6(+) populations were significantly increased in SLE patients (n=70) when compared with healthy controls (n=48). Surprisingly, only CD4(+)CXCR5(hi)PD-1(hi)Bcl-6(+) cTfh cells, rather than CD4(+)CXCR5(hi)PD-1(hi) population, were positively correlated with SLEDAI and anti-dsDNA antibodies...
November 3, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27816669/the-bank1-sle-risk-variants-are-associated-with-alterations-in-peripheral-b-cell-signaling-and-development-in-humans
#20
Elizabeth M Dam, Tania Habib, Janice Chen, Andrew Funk, Veronika Glukhova, Mel Davis-Pickett, Shan Wei, Richard James, Jane H Buckner, Karen Cerosaletti
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the development of autoantibodies that drive disease pathogenesis. Genetic studies have associated nonsynonymous variants in the BANK1 B cell scaffolding gene with susceptibility to SLE and autoantibodies in lupus. To determine how the BANK1 SLE-risk variants contribute to the dysregulated B cell program in lupus, we performed genotype/phenotype studies in human B cells. Targeted phospho-proteomics were used to evaluate BCR/CD40 signaling in human B cell lines engineered to express the BANK1 risk or non-risk variant proteins...
November 2, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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