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Clinical Immunology: the Official Journal of the Clinical Immunology Society

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https://www.readbyqxmd.com/read/28531376/immune-cell-signaling-in-autoimmune-diseases
#1
REVIEW
George C Tsokos, Noel R Rose
On September 20, 2016 the American Autoimmune Related Disease Association convened a selected group of 16 experts in Washington DC to discuss current issues and future directions of research in autoimmune diseases from the cell signaling perspective. The major topics considered included new findings on the follicular T cell cells in mice, their metabolic patterns and their control by the newly discovered T follicular regulatory cells. Current work on the metabolic pathways deemed important for the function of T cells was presented...
May 19, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28506921/decrease-of-blood-anti-%C3%AE-1-3-galactose-abs-levels-in-multiple-sclerosis-ms-and-clinically-isolated-syndrome-cis-patients
#2
L Le Berre, J Rousse, P-A Gourraud, B-M Imbert-Marcille, A Salama, G Evanno, G Semana, A Nicot, E Dugast, P Guérif, C Adjaoud, T Freour, S Brouard, F Agbalika, R Marignier, D Brassat, D-A Laplaud, E Drouet, V Van Pesch, J-P Soulillou
The etiology of multiple sclerosis (MS) remains elusive. Among the possible causes, the increase of anti-Neu5Gc antibodies during EBV primo-infection of Infectious mononucleosis (IMN) may damage the integrity of the blood-brain barrier facilitating the transfer of EBV-infected B cells and anti-EBV T cell clones in the brain. We investigated the change in titers of anti-Neu5Gc and anti-α1,3 Galactose antibodies in 49 IMN, in 76 MS, and 73 clinically isolated syndrome (CIS) patients, as well as age/gender-matched healthy individuals...
May 18, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28526333/systemic-manifestations-of-primary-sj%C3%A3-gren-s-syndrome-in-the-nod-b10sn-h2-b-j-mouse-model
#3
Jeremy Kiripolsky, Long Shen, Yichen Liang, Alisa Li, Lakshmanan Suresh, Yun Lian, Quan-Zhen Li, Daniel P Gaile, Jill M Kramer
Animal models that recapitulate human disease are crucial for the study of Sjögren's Syndrome (SS). While several SS mouse models exist, there are few primary SS (pSS) models that mimic systemic disease manifestations seen in humans. Similar to pSS patients, NOD.B10Sn-H2(b)/J (NOD.B10) mice develop exocrine gland disease and anti-nuclear autoantibodies. However, the disease kinetics and spectrum of extra-glandular disease remain poorly characterized in this model. Our objective was to characterize local and systemic SS manifestations in depth in NOD...
May 16, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28522286/increased-proportions-of-functionally-impaired-regulatory-t-cell-subsets-in-systemic-sclerosis
#4
Emese Ugor, Diána Simon, Giovanni Almanzar, Ramóna Pap, József Najbauer, Péter Németh, Péter Balogh, Martina Prelog, László Czirják, Tímea Berki
Treg abnormalities have been implicated in the pathogenesis of systemic sclerosis (SSc). Treg subpopulations and their cytokines, IL-10 and TGF-β in the peripheral blood of early stage SSc patients were investigated. We hypothesized that epigenetically regulated methylation of the FOXP3 promoter and enhancer regions are altered in Tregs of SSc patients, which might be involved in the T cell imbalance. CD4+CD25+Foxp3+CD127- Treg cells were significantly elevated in patients with diffuse cutaneous SSc and in patients with anti-Scl-70/RNA-Pol-III autoantibody positivity and with lung fibrosis...
May 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28511912/inhibition-of-kdm4a-activity-as-a-strategy-to-suppress-interleukin-6-production-and-attenuate-colitis-induction
#5
Kazuhiro Ishiguro, Osamu Watanabe, Masanao Nakamura, Takeshi Yamamura, Masanobu Matsushita, Hidemi Goto, Yoshiki Hirooka
4-Chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) functions as a hapten and fluoresces upon binding to proteins. Therefore, fluorescence visualization of hapten-proteins is a feature of the colitis induced by NBD-Cl. Using this colitis model, we located activated fibroblasts in the vicinity of hapten-proteins upon colitis induction and observed interleukin (IL)-6 production in the activated fibroblasts. We screened herbal ingredients using primary fibroblasts stimulated with tumor necrosis factor α (TNF-α) and found the suppressive action of Atractylodin on IL-6 production...
May 13, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28506920/regulatory-b-cells-in-rheumatoid-arthritis-alterations-in-patients-receiving-anti-tnf-therapy
#6
Zsuzsanna Bankó, Judit Pozsgay, Tamás Gáti, Bernadette Rojkovich, Ilona Ujfalussy, Gabriella Sármay
Cytokines, including tumor necrosis factor alpha (TNFα) are involved in Rheumatoid arthritis (RA) pathogenesis by augmenting autoimmunity, sustaining long term inflammation in the synovium, and promoting joint damage. Anti-TNF therapy is one of the most efficient and widely used therapies for RA, although its mechanism is not clarified yet. Earlier we demonstrated that RA patients have a reduced number of IL-10 producing regulatory B cells (B10 cells) as compared to healthy individuals and they are functionally impaired...
May 12, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28502680/semaphorin-3a-is-a-key-player-in-the-pathogenesis-of-asthma
#7
Ronen Cozacov, Katlin Halasz, Tharwat Haj, Zahava Vadasz
Immune semaphorins are key players in regulating immune mediated inflammation. Semaphorin3A (sema3A) a secreted and membrane bound member of this family, is well reported for its properties in maintaining self-tolerance. Semaphorin3A was recognized to be a marker for T-regulatory cells (Tregs), and as such is a useful tool for assessing the status of these cells in preventing immune mediated diseases. This study was designed aiming to evaluate how sema3A is possibly involved in bronchial asthma. Here, we found sema3A serum levels and the expression of sema3A on Tregs significantly lower in patients with moderate to severe asthma when compared to healthy individuals...
May 11, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28502679/the-association-between-semaphorin-3a-levels-and-gluten-free-diet-in-patients-with-celiac-disease
#8
Aharon Kessel, Chen Lin, Zahava Vadasz, Regina Peri, Nasren Eiza, Drora Berkowitz
Celiac disease (CD) is an inflammatory disease affecting the small intestine. We aim to assess serum level and expression of semaphorin 3A (Sema3A) on T regulatory (Treg) cells in CD patients. Twenty-six newly diagnosed celiac patients, 13 celiac patients on a gluten-free diet and 16 healthy controls included in the study. Sema3A protein level in the serum of celiac patients was significantly higher compared to healthy group (7.17±1.8ng/ml vs. 5.67±1.5ng/ml, p=0.012). Sema3A expression on Treg cells was statistically lower in celiac patients compared to healthy subjects (p=0...
May 11, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28502678/il-10-producing-regulatory-b-cells-b10-cells-il-17-t-cells-and-autoantibodies-in-systemic-sclerosis
#9
Athanasios Mavropoulos, Christos Liaskos, Theodora Simopoulou, Dimitrios P Bogdanos, Lazaros I Sakkas
We aimed to analyze IL-10+ Breg (B10) cells, found to be reduced in systemic sclerosis (SSc), in relation to SSc-specific autoAbs and IL-17+ and IFNγ+ T cells in SSc. Peripheral blood B10 cells from 26 patients with SSc positive for anti-Topo I or anti-Cen autoAbs, and 12 healthy controls (HC) were studied by flow cytometry. IL-17+ and IFNγ+ T cells were also studied. B10 cells did not correlate with anti-Topo I or anti-Cen Ab levels but were inversely correlated with IL-17+ CD3+ cells and IFNγ+ CD3+ cells...
May 11, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28501589/genetic-modifiers-of-multiple-sclerosis-progression-severity-and-onset
#10
A Dessa Sadovnick, Anthony L Traboulsee, Yinshan Zhao, Cecily Q Bernales, Mary Encarnacion, Jay P Ross, Irene M Yee, Maria G Criscuoli, Carles Vilariño-Güell
The genetic contribution to clinical outcomes for multiple sclerosis (MS) has yet to be defined. We performed exome sequencing analysis in 100 MS patients presenting opposite extremes of clinical phenotype (discovery cohort), and genotyped variants of interest in 2016 MS patients (replication cohort). Linear and logistic regression analyses were used to identify significant associations with disease course, severity and onset. Our analysis of the discovery cohort nominated 38 variants in 21 genes. Replication analysis identified PSMG4 p...
May 10, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28487087/recurrent-respiratory-tract-infections-rrti-in-the-elderly-a-late-onset-mild-immunodeficiency
#11
Esther van de Vosse, Monique M van Ostaijen-Ten Dam, René Vermaire, Els M Verhard, Jacqueline L Waaijer, Jaap A Bakker, Sandra T Bernards, Hermann Eibel, Maarten J van Tol, Jaap T van Dissel, Margje H Haverkamp
Elderly with late-onset recurrent respiratory tract infections (RRTI) often have specific anti-polysaccharide antibody deficiency (SPAD). We hypothesized that late-onset RRTI is caused by mild immunodeficiencies, such as SPAD, that remain hidden through adult life. We analyzed seventeen elderly RRTI patients and matched controls. We determined lymphocyte subsets, expression of BAFF receptors, serum immunoglobulins, complement pathways, Pneumovax-23 vaccination response and genetic variations in BAFFR and MBL2...
May 6, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28487086/an-evaluation-of-the-trec-assay-with-regard-to-the-integration-of-scid-screening-into-the-dutch-newborn-screening-program
#12
Maartje Blom, Ingrid Pico-Knijnenburg, Marja Sijne-van Veen, Anita Boelen, Robbert G M Bredius, Mirjam van der Burg, Peter C J I Schielen
Newborn screening of severe combined immunodeficiency through the detection of T-cell receptor excision circles will provide the opportunity of treating before the occurrence of life-threatening infections. With the EnLite Neonatal TREC assay (PerkinElmer) and end-point PCR, 39 samples (3.0%) of 1295 heel prick cards of the Dutch newborn screening program required a retest after initial analysis. After retest, 21 samples (1.62%) gave TREC levels below cut-off. A significant reduction in TREC levels was observed in heel prick cards stored for three months (n=33) and one year (n=33)...
May 6, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28478106/igg4-related-disease-in-autoimmune-lymphoproliferative-syndrome
#13
LETTER
Annick A J M van de Ven, Maximilian Seidl, Vanessa Drendel, Annette Schmitt-Graeff, Reinhard E Voll, Anne Rensing-Ehl, Carsten Speckmann, Stephan Ehl, Klaus Warnatz, Florian Kollert
A patient with autoimmune lymphoproliferative disorder (ALPS) developed IgG4-related disease. In retrospect, he had high levels of serum IgG4 for several years prior to presenting with IgG4-related pancreatitis. These high IgG4 levels were masked by hypergammaglobulinemia, a common feature of ALPS. We next screened 18 ALPS patients; four of them displayed increased levels of IgG4. Hence, IgG4-related disease should be considered in ALPS patients, especially in those manifesting lymphocytic organ infiltration or excessive hypergammaglobulinaemia...
May 3, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28478105/the-value-of-rituximab-treatment-in-primary-sj%C3%A3-gren-s-syndrome
#14
Gwenny M Verstappen, Jolien F van Nimwegen, Arjan Vissink, Frans G M Kroese, Hendrika Bootsma
The rationale for B-cell depletion therapy with rituximab in pSS relies upon the well-established role of B-cell hyperactivity in immunopathogenesis. In line with this notion, several biomarkers of B-cell activity are significantly affected by treatment, both in the target organs and periphery. In contrast to most biological outcomes, clinical outcomes are not consistent between studies. Although two large RCTs did not meet their primary endpoint, several beneficial clinical effects of treatment have been shown...
May 3, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28478104/what-can-sj%C3%A3-gren-s-syndrome-like-disease-in-mice-contribute-to-human-sj%C3%A3-gren-s-syndrome
#15
Ammon B Peck, Cuong Q Nguyen
For decades, Sjögren's syndrome (SS) and Sjögren's syndrome-like (SS-like) disease in patients and mouse models, respectively, have been intensely investigated in attempts to identify the underlying etiologies, the pathophysiological changes defining disease phenotypes, the nature of the autoimmune responses, and the propensity for developing B cell lymphomas. An emerging question is whether the generation of a multitude of mouse models and the data obtained from their studies is actually important to the understanding of the human disease and potential interventional therapies...
May 3, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28476436/genetics-of-sj%C3%A3-gren-s-syndrome
#16
Leyla Y Teos, Ilias Alevizos
The pathogenesis of Sjögren's syndrome has not been elucidated. There has been evidence that genetics play an important role in the development of this disease from earlier studies. However, till now only a number of genes have been identified to be associated with SS, and these have only a weak or moderate effect. In this review we summarize the findings of the genetics studies and emphasize the need of large multicenter projects that will increase the sample sizes to provide more meaningful associations, as is the case in other common autoimmune diseases...
May 3, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28476437/sjogren-s-syndrome-from-the-perspective-of-ophthalmology
#17
Eric Kuklinski, Penny A Asbell
Sjogren's syndrome (SS) is an autoimmune disease affecting the lacrimal glands resulting in dry eye disease (DED). Ophthalmologists may be the first line of detection of Sjogren's syndrome given the frequency of DED in SS and that dry eye is often the presenting symptom. Numerous symptom questionnaires and tests have been developed to help diagnose DED, but as of yet, there is no "gold standard." Minimally invasive objective metrics are needed for a reliable diagnosis of DED. Currently there is no single test to diagnose SS-associated DED...
May 2, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28461110/granzyme-b-producing-b-cells-in-renal-transplant-patients
#18
Jiqiao Zhu, Ye Zeng, Sebastian Dolff, Anja Bienholz, Monika Lindemann, Alexandra Brinkhoff, Manfred Schedlowski, Shilei Xu, Ming Sun, Hana Guberina, Julia Kirchhof, Andreas Kribben, Oliver Witzke, Benjamin Wilde
OBJECTIVES: A separate subset of Granzyme B (GrB) producing B-cells regulating T-cell mediated immunity has been identified. In the present study, we investigated the role of GrB(+) B-cells in renal transplant patients (RTX). METHODS: 12 healthy controls (HC) and 26 RTX patients were enrolled. In addition, 19 healthy volunteers treated with cyclosporine A (CsA) were enrolled. GrB(+) B-cells were determined via flow cytometry. RESULTS: RTX Patients showed a diminished fraction of GrB(+) B-cells as compared to HC...
April 28, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28461109/influence-of-drug-molecules-on-regulatory-b-cells
#19
Kahina Amrouche, Christophe Jamin
By their suppressive functions, regulatory B (Breg) cells are considered as key elements in the control and development of various disease states. Many signals can induce Bregs in vivo and in vitro and often from heterogeneous populations. Several specific signals delivered in a timely immunological context contribute to the establishment of Bregs. These are endogenous and physiological signals or stimuli, widely discussed in the literature participating in the establishment of an effective immune response...
April 28, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28461108/breg-cells-in-hashimoto-s-thyroiditis-isolated-or-associated-to-further-organ-specific-autoimmune-diseases
#20
Maria Giulia Santaguida, Ilenia Gatto, Giorgio Mangino, Camilla Virili, Ilaria Stramazzo, Poupak Fallahi, Alessandro Antonelli, Maria Segni, Giovanna Romeo, Marco Centanni
Hashimoto thyroiditis (HT) may occur isolated or associated with other non-endocrine autoimmune disorders (NEAD). No data are available about Breg cells in these disorders and this represented the aim of the study. Th17 and Breg cells subset were characterized on peripheral blood mononuclear cells isolated from 18 healthy donors (HD), 19 patients with isolated HT and 26 patients with HT+NEAD. Th17 were higher in patients with isolated HT than in HD but no further changes were seen in patients with HT+NEAD. CD24(hi)CD38(hi) unstimulated Breg cells were similar in HT patients and in HD, but significantly higher in patients with HT+NEAD than in both HT and in HD...
April 28, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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