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Clinical Immunology: the Official Journal of the Clinical Immunology Society

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https://www.readbyqxmd.com/read/30099194/myd88-signaling-in-t-regulatory-cells-by-endogenous-ligands-dampens-skin-inflammation-in-filaggrin-deficient-mice
#1
Sabine Hoff, Michiko K Oyoshi, Jason L Hornick, Raif S Geha
Mutations in filaggrin are associated with atopic dermatitis. Filaggrin-deficient flaky tail (Flgft/ft ) mice develop spontaneous inflammatory skin lesion that wax and wane. We show that loss of MyD88 promotes the persistence of skin lesions in Flgft/ft mice and exaggerates their expression of the Th17-associated cytokines Il7a and Il22. The development and persistence of skin lesions in Flgft/ft mice was independent of the microbiota. MyD88-mediated signals are shown to be important for the accumulation of T regulatory cells (Tregs) in lesional skin of Flgft/ft mice...
August 9, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/30077805/formononetin-attenuated-allergic-diseases-through-inhibition-of-epithelial-derived-cytokines-by-regulating-e-cadherin
#2
Li Lianqu, Wang Yan, Wang Xiaoyu, Tao Yu, Bao Kaifa, Hua Yongqing, Jiang Guorong, Hong Min
Radix Astragali, has long been used to alleviate allergic diseases (ADs). Formononetin is one of the major active components in Radix Astragali, but its mechanism on ADs is not definitively known. The fluorescein isothiocyanate isomer-induced atopic contact dermatitis mouse model and poly I:C or lipopolysaccharide-treated HaCaT cells were used to examine thymic stromal lymphopoietin (TSLP)/interleukin (IL)-33 production and expression of E-cadherin. After administration of formononetin, TSLP/IL-33 levels decreased both in vitro and in vivo, while E-cadherin was increased in vivo and restored in vitro...
August 2, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/30077013/epitope-mapping-of-anti-alk-antibodies-in-children-with-anaplastic-large-cell-lymphoma
#3
Fabian Knörr, Simone Weber, Vijay K Singh, Karen Pulford, Alfred Reiter, Wilhelm Woessmann, Christine Damm-Welk
Patients with Nucleophosmin (NPM)-Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) mount ALK autoantibodies. The titer of these autoantibodies inversely correlates with the risk of relapse. The epitopes recognized by these autoantibodies in NPM-ALK might be associated with different ALK-antibody levels. We used overlapping peptide microarray technology to analyze epitope-binding to NPM-ALK by plasma or serum from 129 ALK-positive ALCL patients and 21 controls. Antibodies present in sera from ALCL patients bound to epitopes mainly in the C-terminal region of the ALK portion of NPM-ALK (amino acid positions 469-496, 561-588, 617-644)...
August 1, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/30075290/deficiencies-in-the-cd19-complex
#4
REVIEW
Marjolein W J Wentink, Menno van Zelm, Jacques J M van Dongen, Klaus Warnatz, Mirjam van der Burg
Signaling via the CD19-complex, consisting of CD19, CD81, CD21 and CD225, is critically important for B-cell development, differentiation and maturation. In this complex, each protein has its own distinct function. Over the past decade, 15 patients with antibody deficiency due to deficiencies in the CD19-complex have been described. These patients have deficiencies in different complex-members, all caused by either homozygous or compound heterozygous mutations. Although all patients had antibody deficiencies, the clinical phenotype was different per deficient protein...
July 31, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/30063982/autosomal-recessive-agammaglobulinemia-first-case-with-a-novel-tcf3-mutation-from-pakistan
#5
LETTER
Sonia Qureshi, Muhammad Dawood Amir Sheikh, Farah Naz Qamar, Wayne Bainter, Janet Chou, Raif S Geha
Autosomal Recessive Agammaglobulinemia (ARA) is an uncommon type of primary immunodeficiency characterized by mutations in genes responsible for early B cell differentiation and function. One such gene is the TCF3 gene, which encodes a transcription factor important for immunoglobulin gene expression. We present the case of a 9 year old girl with history of diarrhea and recurrent pneumonias. Laboratory investigation showed significantly reduced levels of immunoglobulins along with a significant fall in the number of CD19+ cells...
July 28, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/30063981/th1-skewed-profile-and-excessive-production-of-proinflammatory-cytokines-in-a-nfkb1-deficient-patient-with-cvid-and-severe-gastrointestinal-manifestations
#6
Romina Dieli-Crimi, Mónica Martínez-Gallo, Clara Franco-Jarava, Maria Antolin, Laura Blasco, Ida Paramonov, Maria E Semidey, Antoni Álvarez Fernández, Xavier Molero, Julio Velásquez, Andrea Martín-Nalda, Ricardo Pujol-Borrell, Roger Colobran
Monoallelic loss-of-function mutations in NFKB1 were recently recognized as the most common monogenic cause of common variable immunodeficiency (CVID). The prototypic clinical phenotype of NFKB1-deficient patients includes common CVID features, such as hypogammaglobulinaemia and sinopulmonary infections, plus other highly variable individual manifestations. Here, we describe a patient with a profound CVID phenotype and severe gastrointestinal manifestations, including chronic and recurrent diarrhoea. Using an NGS customized panel of 323 genes related to primary immunodeficiencies, we identified a novel monoallelic loss-of-function mutation in NFKB1 leading to a truncated protein (c...
July 28, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/30056130/toll-like-receptor-9-ligands-increase-type-i-interferon-induced-b-cell-activating-factor-expression-in-chronic-rhinosinusitis-with-nasal-polyposis
#7
Jun Xu, Jin-Woo Lee, Soo-Kyoung Park, Sung-Bok Lee, Young-Hoon Yoon, Sun-Hee Yeon, Ki-Sang Rha, Ji-Ae Choi, Chang-Hwa Song, Yong Min Kim
B-cell activating factor (BAFF) has been proposed to play a crucial role in the pathogenesis of chronic rhinosinusitis with nasal polyp (CRSwNP). The aim of this study was to evaluate the role of toll-like receptor (TLR) 9-mediated BAFF activation on the pathogenesis of CRSwNP. NP and uncinate tissue (UT) were obtained from patients with CRSwNP or CRS without NP, and control subjects. The expression of TLR9, high mobility group box-1 protein (HMGB1), type I interferon (IFN), BAFF, and anti-double stranded DNA (dsDNA) antibody were examined in the tissues and the cultured dispersed NP cells (DNPCs)...
July 26, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/30053428/clinical-and-molecular-features-of-x-linked-hyper-igm-syndrome-an-experience-from-north-india
#8
Amit Rawat, Babu Mathew, Vignesh Pandiarajan, Ankur Jindal, Madhubala Sharma, Deepti Suri, Anju Gupta, Shubham Goel, Adil Karim, Biman Saikia, Ranjana W Minz, Kohsuke Imai, Shigeaki Nonoyama, Osamu Ohara, Silvia Clara Giliani, Luigi D Notarangelo, Koon-Wing Chan, Yu-Lung Lau, Surjit Singh
X-linked hyper IgM Syndrome (XLHIGM), the most frequent form of the Hyper IgM syndromes is a primary immune deficiency resulting from a mutation in the CD40 ligand gene (CD40LG). We analyzed the clinical and laboratory features of ten patients with XLHIGM, who were diagnosed at a tertiary care hospital in North India. Most common infections were sinopulmonary infections (80%) and diarrhea (50%). Sclerosing cholangitis and necrotising fasciitis were noted in one patient each. Three novel mutations in CD40LG (c...
July 25, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/30048691/diagnosis-of-dock8-deficiency-using-flow-cytometry-biomarkers-an-egyptian-center-experience
#9
Safa S Meshaal, Rabab E El Hawary, Alia Eldash, Bodo Grimbacher, Nadezhda Camacho-Ordonez, Dalia S Abd Elaziz, Nermeen M Galal, Jeannette A Boutros, Shereen M Shawky, Aisha M Elmarsafy
In the past few years, several genes were shown to be implicated in various forms of the Hyper Immunoglobulin E syndrome. The present study is the first to describe a cohort of DOCK8 deficiency patients from Egypt. The study included 15 patients with features of combined immunodeficiency (CID) suggestive of DOCK8 deficiency. Flow cytometry was used for evaluation of DOCK8 expression and studying different immunological characteristics of those patients including evaluation of Th17, Tregs, T and B lymphocytes differentiation and the effect of the DOCK8 deficiency on the activation of the STAT3...
July 24, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/30048690/high-frequencies-of-asymptomatic-epstein-barr-virus-viremia-in-affected-and-unaffected-individuals-with-ctla4-mutations
#10
Akihiro Hoshino, Kay Tanita, Kenji Kanda, Ken-Ichi Imadome, Yoshiaki Shikama, Takahiro Yasumi, Kohsuke Imai, Masatoshi Takagi, Tomohiro Morio, Hirokazu Kanegane
Patients with CTLA4 mutations present with autoimmune diseases, lymphoproliferation, and hypogammaglobulinemia, and a subset of patients developed Epstein-Barr virus (EBV)-associated malignancies, suggesting an impaired immune function against EBV. Here we investigated EBV infection in individuals with CTLA4 mutations. We measured EBV viral DNA in healthy individuals, individuals with autoimmune diseases, and individuals with CTLA4 mutations. In addition, we evaluated the numbers and function of EBV-specific T cells, invariant NKT cells, and NK cells...
July 24, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/30036638/anti-polysaccharide-and-anti-diphtheria-protective-antibodies-after-13-valent-pneumococcal-conjugate-vaccination-in-rheumatoid-arthritis-patients-under-immunosuppressive-therapy
#11
Sara Caporuscio, Roberto Ieraci, Guido Valesini, Raffaela Teloni, Sabrina Mariotti, Francesca Romana Spinelli, Claudia Ferlito, Simonetta Salemi, Andrea Picchianti Diamanti, Giorgia Meneguzzi, Milica Markovic, Mayla Sgrulletti, Christina von Hunolstein, Luisa Ralli, Antonietta Pinto, Gerardo Salerno, Marco Canzoni, Maria Laura Sorgi, Bruno Laganà, Roberta Di Rosa, Roberto Nisini, Raffaele D'Amelio
Immunogenicity of 13-valent pneumococcal polysaccharide (PnPS) conjugate vaccine (PCV13) was evaluated in 38 rheumatoid arthritis patients under immunosuppressive treatment and 20 healthy controls (HC). Antibodies to all PnPS and diphtheria-toxin analogue conjugate protein were measured pre- (T0), 1 (T1), 6 (T2), 12 (T3) months post-immunization. Patients and HC had similar response to individual PnPS. Mean antibody levels to all PnPS but one doubled at T1 compared with T0, with T3 persistence for only 8-7/13 PnPS...
July 21, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/30036637/cd4-t-cell-loss-and-th2-and-th17-bias-are-associated-with-the-severity-of-severe-fever-with-thrombocytopenia-syndrome-sfts
#12
Meng-Meng Li, Wen-Jing Zhang, Xiu-Fang Weng, Ming-Yue Li, Jia Liu, Yan Xiong, Shu-E Xiong, Cong-Cong Zou, Hua Wang, Meng-Ji Lu, Dong-Liang Yang, Cheng Peng, Xin Zheng
Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging infectious disease caused by a novel bunyavirus with high mortality. Immune suppression is thought to be crucial in disease progression. However, data on immune responses during SFTS are scarce. This study aimed to evaluate the changes in CD4 T-cell subsets throughout the entirety of infection and analyse their relationships with disease severity in SFTS patients. In parallel with CD4 T-cell depletion, decreased Th1, Th2 and Treg numbers, but comparable Th17-cell numbers, were observed in deceased patients compared with those in surviving patients...
July 20, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/30025819/effects-of-hla-status-and-her2-status-on-outcomes-in-breast-cancer-patients-at-risk-for-recurrence-implications-for-vaccine-trial-design
#13
Doreen O Jackson, Francois A Trappey, G Travis Clifton, Timothy J Vreeland, Kaitlin M Peace, Diane F Hale, Jennifer K Litton, James L Murray, Sonia A Perez, Michael Papamichail, Elizabeth A Mittendorf, George E Peoples
Immunotherapy, using peptide-based cancer vaccines is being studied to assess its potential in breast cancer. Trials of HLA-restricted peptide vaccines have been difficult to enroll given HLA subtype restrictions. It is necessary to determine the prognostic significance of HLA-status in breast cancer if patients who are ineligible to receive a vaccine due to their HLA-status are used as controls. The impact of targeted tumor associated antigen expression, when it effects eligibility is also important. We examined control patients from two randomized phase II trials that tested HER2-peptide vaccines to determine the effect of HLA-A2 status and HER2 expression on disease-free survival...
July 17, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/30025818/systemic-lupus-erythematosus-myasthenia-gravis-overlap-syndrome-presentation-and-treatment-depend-on-prior-thymectomy
#14
Scott Brian Minchenberg, Geeta Chaparala, Zachary Oaks, Katalin Banki, Andras Perl
In this study, we investigated four patients who met the diagnostic criteria for overlapping systemic lupus erythematosus (SLE) and myasthenia gravis (MG) but responded differently to treatment. All patients were acetylcholine receptor (AChR) and antinuclear antibody positive at the time of SLE diagnosis. Two patients presented with SLE who have been effectively treated with cholinesterase inhibitors for MG. These patients developed SLE with photosensitivity, rash, and arthritis post thymectomy, which had been performed 29 years and 40 years earlier, respectively...
July 17, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/30006120/hla-g-protein-expression-in-colorectal-cancer-evaluated-by-immunohistochemistry-and-western-blot-analysis-its-expression-characteristics-remain-enigmatic
#15
Marloes Swets, Anne Wouters, Daniëlle Krijgsman, Ronald L P van Vlierberghe, Arnoud Boot, Jaap D van Eendenburg, Tom van Wezel, Hans Gelderblom, Cornelis J H van de Velde, Peter J van den Elsen, Peter J K Kuppen
HLA-G protein expression could play a role in evasion of tumor immune surveillance. Accumulating evidence demonstrates that HLA-G is expressed in different types of malignancies, including colorectal cancer (CRC). The purpose of the current study was to further unravel whether HLA-G protein expression could play a role in immune evasion of CRC. Therefore, to firmly establish HLA-G protein expression, eight early passage human CRC cell lines and five human rectal cancer tissues were analyzed by western blot analysis...
July 10, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/30004016/hydroxychloroquine-as-a-novel-therapeutic-approach-in-mast-cell-activation-diseases
#16
Eric Espinosa, Salvatore Valitutti, Michel Laroche, Camille Laurent, Pol André Apoil, Olivier Hermine, Michel Lavit, Carle Paul, Cristina Bulai Livideanu
There is no therapeutic agent approved in cutaneous mastocytosis and mast cell activation syndrome. We report the efficacy of hydroxychloroquine in four patients with cutaneous mastocytosis (n = 2) and mast cell activation syndrome (n = 2). We show that this molecule reduces the long-term survival of primary human mast cells, interferes with lysosome function and leads to the accumulation of non-functional tryptase in the mast cell granules. Furthermore, hydroxychloroquine decreases the production of pro-inflammatory mediators...
July 10, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29990590/novel-minor-hla-dr-associated-antigens-in-type-1-diabetes
#17
Denise Müller, Tanja Telieps, Anne Eugster, Christina Weinzierl, Manja Jolink, Anette-Gabriele Ziegler, Ezio Bonifacio
Type 1 diabetes is an autoimmune disease leading to insulin deficiency. Autoantibodies to beta cell proteins are already present in the asymptomatic phase of type 1 diabetes. Recent findings have suggested a number of additional minor autoantigens in patients with type 1 diabetes. We have established luciferase immunoprecipitation systems (LIPS) for anti-MTIF3, anti-PPIL2, anti-NUP50 and anti-MLH1 and analyzed samples from 500 patients with type 1 diabetes at onset of clinical disease and 200 healthy individuals who had a family history of type 1 diabetes but no evidence of beta cell autoantibodies...
July 7, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29981383/hydroxychloroquine-efficiently-suppresses-inflammatory-responses-of-human-class-switched-memory-b-cells-via-toll-like-receptor-9-inhibition
#18
Masataka Torigoe, Kei Sakata, Akina Ishii, Shigeru Iwata, Shingo Nakayamada, Yoshiya Tanaka
Hydroxychloroquine is widely used for autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Although B cells contribute to the pathogenesis of these diseases, the action of hydroxychloroquine on B cells remains unclear. Here we examined the effects of hydroxychloroquine on functions of B cell subsets. Hydroxychloroquine efficiently inhibited the mammalian target of rapamycin complex 1, differentiation of CD19+ IgD- CD27+ class-switched memory B cells to plasmablasts and their IgG production, under stimulation with CpG, a Toll-like receptor (TLR)-9 ligand...
July 4, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29966714/hematological-malignancies-associated-with-primary-immunodeficiency-disorders
#19
REVIEW
Lucy Duan, Eyal Grunebaum
Primary Immunodeficiency disorders (PID) have been increasingly recognized in association with hematologic malignancies. To better appreciate this association, a systemic search of the Ovid MEDLINE database was performed with terms related of hematologic malignancies and all PID described in the 2017 International Union of Immunological Societies Expert Committee for Primary Immunodeficiency. More than 60 PID distinct PID, caused by cell-intrinsic and extrinsic mechanisms were associated with diverse hematologic malignancies...
July 4, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/30018024/yb-1-increases-glomerular-but-decreases-interstitial-fibrosis-in-cni-induced-nephropathy
#20
Lydia Gibbert, Daniela Hermert, Jialin Wang, Daniel M Breitkopf, Christina Alidousty, Matthias Neusser, Clemens D Cohen, Elisabeth Gröne, Iris Macheleidt, Thomas Rauen, Gerald S Braun, Jürgen Floege, Tammo Ostendorf, Ute Raffetseder
Calcineurin inhibitors (CNIs) are a cornerstone of the current treatment in solid organ transplantation and autoimmune disease. However, CNIs also bear deleterious effects as they cause glomerular and tubulointerstitial fibrosis in the kidney. We recently identified Y-box protein-1 (YB-1) as a novel downstream effector of CNI-signaling in the cytoplasm of glomerular cells. In the present study, we corroborate the pro-fibrotic role of YB-1 in glomeruli of patients under CNI-treatment. Such effects in glomeruli are significantly mitigated in CNI-treated mice with half-normal YB-1 expression (Yb1+/- )...
July 3, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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