Imaging

@article{sawaf_defective_2018,

title = {Defective BTLA functionality is rescued by restoring lipid metabolism in lupus CD4+ Ŧ cells},

author = {Matthieu Sawaf and Jean-Daniel Fauny and Renaud Felten and Flora Sagez and Jacques-Eric Gottenberg and Hélène Dumortier and Fanny Monneaux},

doi = {10.1172/jci.insight.99711},

issn = {2379-3708},

year  = {2018},

date = {2018-01-01},

journal = {JCI insight},

volume = {3},

number = {13},

abstract = {Coinhibitory receptors play an important role in the prevention of autoimmune diseases, such as systemic lupus erythematosus (SLE), by limiting T cell activation. B and T lymphocyte attenuator (BTLA) is an inhibitory receptor, similar to cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD1), that negatively regulates the immune response. The role of BTLA in the pathogenesis of autoimmune diseases in humans and, more specifically, in SLE is largely unknown. We investigated BTLA expression on various T cell subsets, and we did not observe significant variations of BTLA expression between lupus patients and healthy controls. However, the enhancement of BTLA expression after activation was significantly lower in SLE patients compared with that in healthy controls. Furthermore, we found an impaired capacity of BTLA to inhibit T cell activation in SLE due to a poor BTLA recruitment to the immunological synapse following T cell stimulation. Finally, we demonstrated that defective BTLA function can be corrected by restoring intracellular trafficking and by normalizing the lipid metabolism in lupus CD4+ T cells. Collectively, our results evidence that the BTLA signaling pathway is altered in SLE T cells and highlight the potential of targeting this pathway for the development of new therapeutic strategies in lupus.},

keywords = {80 and over, Adolescent, Adult, Aged, Autoimmune Diseases, Autoimmunity, CD4-Positive T-Lymphocytes, Cell Proliferation, CTLA-4 Antigen, Dumortier, Female, France, Humans, I2CT, Imagerie, Immunologic, Immunology, Lipid Metabolism, lupus, Lupus Erythematosus, Lymphocyte Activation, Male, Middle Aged, Monneaux, Programmed Cell Death 1 Receptor, Receptors, Signal Transduction, Systemic, Team-Dumortier, Young Adult},

pubstate = {published},

tppubtype = {article}

}

@article{jacquemin_ox40_2015,

title = {OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting Ŧ Follicular Helper Response},

author = {Clément Jacquemin and Nathalie Schmitt and Cécile Contin-Bordes and Yang Liu and Priya Narayanan and Julien Seneschal and Typhanie Maurouard and David Dougall and Emily Spence Davizon and Hélène Dumortier and Isabelle Douchet and Loïc Raffray and Christophe Richez and Estibaliz Lazaro and Pierre Duffau and Marie-Elise Truchetet and Liliane Khoryati and Patrick Mercié and Lionel Couzi and Pierre Merville and Thierry Schaeverbeke and Jean-François Viallard and Jean-Luc Pellegrin and Jean-François Moreau and Sylviane Muller and Sandy Zurawski and Robert L Coffman and Virginia Pascual and Hideki Ueno and Patrick Blanco},

doi = {10.1016/j.immuni.2015.05.012},

issn = {1097-4180},

year  = {2015},

date = {2015-01-01},

journal = {Immunity},

volume = {42},

number = {6},

pages = {1159--1170},

abstract = {Increased activity of T follicular helper (Tfh) cells plays a major pathogenic role in systemic lupus erythematosus (SLE). However, the mechanisms that cause aberrant Tfh cell responses in SLE remain elusive. Here we showed the OX40 ligand (OX40L)-OX40 axis contributes to the aberrant Tfh response in SLE. OX40L was expressed by myeloid antigen-presenting cells (APCs), but not B cells, in blood and in inflamed tissues in adult and pediatric SLE patients. The frequency of circulating OX40L-expressing myeloid APCs positively correlated with disease activity and the frequency of ICOS(+) blood Tfh cells in SLE. OX40 signals promoted naive and memory CD4(+) T cells to express multiple Tfh cell molecules and were sufficient to induce them to become functional B cell helpers. Immune complexes containing RNA induced OX40L expression on myeloid APCs via TLR7 activation. Our study provides a rationale to target the OX40L-OX40 axis as a therapeutic modality for SLE.},

keywords = {Adolescent, Adult, Aged, Antigen Presentation, B-Lymphocytes, Cell Differentiation, Cells, Cultured, Cytokines, Disease Progression, Dumortier, Female, Helper-Inducer, Humans, I2CT, Immunologic Memory, Inducible T-Cell Co-Stimulator Protein, Lupus Erythematosus, Lymphocyte Activation, Male, Middle Aged, Molecular Targeted Therapy, Myeloid Cells, OX40, OX40 Ligand, Receptors, RNA, Signal Transduction, Systemic, T-Lymphocytes, Team-Dumortier, Toll-Like Receptor 7, Young Adult},

pubstate = {published},

tppubtype = {article}

}

@article{muller_spliceosomal_2008,

title = {Spliceosomal peptide P140 for immunotherapy of systemic lupus erythematosus: results of an early phase II clinical trial},

author = {Sylviane Muller and Fanny Monneaux and Nicolas Schall and Rasho K Rashkov and Boycho A Oparanov and Philippe Wiesel and Jean-Marie Geiger and Robert Zimmer},

doi = {10.1002/art.24027},

issn = {0004-3591},

year  = {2008},

date = {2008-01-01},

journal = {Arthritis and Rheumatism},

volume = {58},

number = {12},

pages = {3873--3883},

abstract = {OBJECTIVE: To assess the safety, tolerability, and efficacy of spliceosomal peptide P140 (IPP-201101; sequence 131-151 of the U1-70K protein phosphorylated at Ser140), which is recognized by lupus CD4+ T cells, in the treatment of patients with systemic lupus erythematosus (SLE). 

METHODS: An open-label, dose-escalation phase II study was conducted in two centers in Bulgaria. Twenty patients (2 male and 18 female) with moderately active SLE received 3 subcutaneous (SC) administrations of a clinical batch of P140 peptide at 2-week intervals. Clinical evaluation was performed using approved scales. A panel of autoantibodies, including antinuclear antibodies, antibodies to extractable nuclear antigens (U1 RNP, SmD1, Ro/SSA, La/SSB), and antibodies to double-stranded DNA (anti-dsDNA), chromatin, cardiolipin, and peptides of the U1-70K protein, was tested by enzyme-linked immunosorbent assay (ELISA). The plasma levels of C-reactive protein, total Ig, IgG, IgG subclasses, IgM, IgA, and IgE, and of the cytokines interleukin-2 and tumor necrosis factor alpha were measured by ELISA and nephelometry. 

RESULTS: IgG anti-dsDNA antibody levels decreased by at least 20% in 7 of 10 patients who received 3 x 200 microg IPP-201101 (group 1), but only in 1 patient in the group receiving 3 x 1,000 microg IPP-201101 (group 2). Physician's global assessment of disease activity scores and scores on the SLE Disease Activity Index were significantly decreased in group 1. The changes occurred progressively in the population of responders, increased in magnitude during the treatment period, and were sustained. No clinical or biologic adverse effects were observed in the individuals, except for some local irritation at the highest concentration. 

CONCLUSION: IPP-201101 was found to be safe and well tolerated by subjects. Three SC doses of IPP-201101 at 200 microg significantly improved the clinical and biologic status of lupus patients.},

keywords = {Adolescent, Adult, Aged, Antibodies, Antinuclear, C-Reactive Protein, DNA, Female, Humans, I2CT, Immunotherapy, Lupus Erythematosus, Male, Middle Aged, Monneaux, Peptide Fragments, Peptides, Severity of Illness Index, Spliceosomes, Systemic, Team-Dumortier, Treatment Outcome, Young Adult},

pubstate = {published},

tppubtype = {article}

}

@article{,

title = {Deficiency of queuine, a highly modified purine base, in transfer RNAs from primary and metastatic ovarian malignant tumors in women},

author = { W. Baranowski and G. Dirheimer and J. A. Jakowicki and G. Keith},

year  = {1994},

date = {1994-01-01},

journal = {Cancer Res},

volume = {54},

number = {16},

pages = {4468-71},

abstract = {The tRNAs from rapidly growing tissues, particularly from neoplasia, often exhibit queuine deficiency. In order to check whether different kinds of ovarian tumors display queuine deficiencies we have analyzed tRNA samples from 16 ovarian malignancies. The tRNAs from histologically normal myometrium (4 samples) and myoma (6 samples) were taken as healthy tissue and benign tumor references. Queuine deficiency was determined by an exchange assay using [8-3H]guanine and tRNA:guanine transglycosylase from Escherichia coli. The mean values of queuine deficiencies in tRNAs were: 10.95 +/- 2.21 (SD) pmol/A260 in gonadal and germ cell tumors (5 cases); 23.75 +/- 7.89 pmol/A260 in primary epithelial tumors (9 cases); and 34.58 +/- 7.18 pmol/A260 in metastatic tumors (2 cases). These values displayed statistically significant differences (P = 0.0003, Kruskal-Wallis test). The queuine deficiencies in tRNAs significantly increased when moving from well-differentiated through moderately differentiated to poorly differentiated tumors, with the highest values found in poorly differentiated metastatic tumors (P = 0.0002, Kruskal-Wallis test). Queuine deficiency determination in tRNAs is proposed as a factor for clinical outcome prognosis of ovarian malignancies.},

note = {0008-5472 

Journal Article},

keywords = {&, Adolescent, Adult, Aged, derivatives/analysis, Female, Gov't, Guanine/*analogs, Human, Middle, Neoplasm/*chemistry, Neoplasms/*chemistry/pathology, Non-U.S., Ovarian, RNA, Support, Transfer/*chemistry},

pubstate = {published},

tppubtype = {article}

}