Pulmonary sarcoidosis is associated with exosomal vitamin D–binding protein and inflammatory molecules Maria-Jose Martinez-Bravo, PhD, Casper J.E. Wahlund,

Slides:

Advertisements

Similar presentations

Serum granzymes and CD30 are increased in children's milk protein sensitive enteropathy and celiac disease Merja T. Augustin, MD, Jorma Kokkonen, MD,

Advertisements

Serum granzymes and CD30 are increased in children's milk protein sensitive enteropathy and celiac disease Merja T. Augustin, MD, Jorma Kokkonen, MD,

Exosome-enclosed microRNAs in exhaled breath hold potential for biomarker discovery in patients with pulmonary diseases Anirban Sinha, MSc, Amit Kumar.

Defective calcium signaling and disrupted CD20–B-cell receptor dissociation in patients with common variable immunodeficiency disorders Annick A.J.M.

Exploring the repertoire of IgE-binding self-antigens associated with atopic eczema Sabine Zeller, MSc, Claudio Rhyner, PhD, Norbert Meyer, MD, Peter.

Repeated FcεRI triggering reveals modified mast cell function related to chronic allergic responses in tissue Jolien Suurmond, MSc, Kim L.L. Habets,

Sytze de Roock, PhD, Arie J

Reduced IFN-γ receptor expression and attenuated IFN-γ response by dendritic cells in patients with atopic dermatitis Eva Gros, MSc, Susanne Petzold,

Ann-Marie M. Schoos, MD, PhD, Jacob D

Hypersensitivity reactions due to nitrile gloves

CD4+ T cells in patients with chronic inflammatory rheumatic disorders show distinct levels of exhaustion Theresa Frenz, PhD, Elena Grabski, PhD, Daniela.

Epithelial proteome profiling suggests the essential role of interferon-inducible proteins in patients with allergic rhinitis Joseph Ndika, PhD, Liisa.

Frank Kirstein, PhD, Natalie E

Reduction of CRKL expression in patients with partial DiGeorge syndrome is associated with impairment of T-cell functions Mauro Giacomelli, PhD, Rajesh.

Estrogen and progesterone decrease let-7f microRNA expression and increase IL-23/IL- 23 receptor signaling and IL-17A production in patients with severe.

Gender differences in the bronchoalveolar lavage cell proteome of patients with chronic obstructive pulmonary disease Maxie Kohler, PhD, AnnSofi Sandberg,

Flow cytometric measurement of STAT1 and STAT3 phosphorylation in CD4+ and CD8+ T cells—clinical applications in primary immunodeficiency diagnostics

Beatriz Garcillán, MS, Marina S

Mass cytometry profiling the response of basophils and the complete peripheral blood compartment to peanut Leticia Tordesillas, PhD, Adeeb H. Rahman,

Exosomes from human macrophages and dendritic cells contain enzymes for leukotriene biosynthesis and promote granulocyte migration Julia Esser, BS, Ulf.

Clara cell 16-kd protein downregulates TH2 differentiation of human naive neonatal T cells Sofi Johansson, MSc, Göran Wennergren, MD, PhD, Nils Åberg,

Frank Kirstein, PhD, Natalie E

Lieuwe D. Bos, MSc, PhD, Peter J. Sterk, MD, PhD, Stephen J

Blood fibrocytes are recruited during acute exacerbations of chronic obstructive pulmonary disease through a CXCR4-dependent pathway Isabelle Dupin,

Cleaved kininogen as a biomarker for bradykinin release in hereditary angioedema Zonne L.M. Hofman, MSc, Steven de Maat, PhD, Chiara Suffritti, PhD, Andrea.

Transmembrane activator and CAML interactor (TACI) haploinsufficiency results in B- cell dysfunction in patients with Smith-Magenis syndrome Javier Chinen,

Miriam Wittmann, MD, Jana Zeitvogel, Dong Wang, MD, Thomas Werfel, MD

Lower airway microbiota and mycobiota in children with severe asthma

Corticosteroid-resistant asthma is associated with classical antimicrobial activation of airway macrophages Elena Goleva, PhD, Pia J. Hauk, MD, Clifton.

Expression of FcɛRI on dendritic cell subsets in peripheral blood of patients with atopic dermatitis and allergic asthma Inge M.J. Beeren, MSc, Marjolein.

Davide Pennino, MSc, Pankaj K

T-box 21 transcription factor is responsible for distorted TH2 differentiation in human peripheral CD4+ T cells Osamu Kaminuma, DVM, PhD, Fujiko Kitamura,

Benjamin T. Prince, MD, Msci, Ashley L. Devonshire, MD, MPH, Kristin A

Chronic cat allergen exposure induces a TH2 cell–dependent IgG4 response related to low sensitization Amedee Renand, PhD, Luis D. Archila, MSc, John.

A peptide derived from the Wiskott-Aldrich syndrome (WAS) protein-interacting protein (WIP) restores WAS protein level and actin cytoskeleton reorganization.

Brent E. Palmer, PhD, Douglas G. Mack, PhD, Allison K

Expression of the cysteinyl leukotriene receptors cysLT1 and cysLT2 in aspirin-sensitive and aspirin-tolerant chronic rhinosinusitis Chris Corrigan,

Chronic rhinosinusitis with nasal polyps is characterized by B-cell inflammation and EBV-induced protein 2 expression Kathryn E. Hulse, PhD, James E.

Nasal mucus proteomic changes reflect altered immune responses and epithelial permeability in patients with allergic rhinitis Peter Valentin Tomazic,

Mammalian target of rapamycin inhibition counterbalances the inflammatory status of immune cells in patients with chronic granulomatous disease Aurélie.

Statins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase

T-bet inhibits innate lymphoid cell–mediated eosinophilic airway inflammation by suppressing IL-9 production Ayako Matsuki, MD, Hiroaki Takatori, MD,

Janina Dose, PhD, Anke Schloesser, PhD, Guillermo G

Biosimilars and drug development in allergic and immunologic diseases

IκB kinase–driven nuclear factor-κB activation in patients with asthma and chronic obstructive pulmonary disease Rosalia Gagliardo, PhD, Pascal Chanez,

What is an “eosinophilic phenotype” of asthma?

Casein-related anaphylaxis after use of an Everlast kickboxing glove

Impaired intestinal tolerance in the absence of a functional complement system Pirkka T. Pekkarinen, MD, Kirsi Vaali, PhD, Hanna Jarva, MD, PhD, Eliisa.

Autophagy: Nobel Prize 2016 and allergy and asthma research

Allergen-specific CD8+ T cells in peanut-allergic individuals

Sara Paveglio, PhD, MS, Erin Bennett, MS, Kelly L. Hawley, PhD, Adam P

Sputum inflammatory cells from patients with allergic rhinitis and asthma have decreased inflammasome gene expression Willie June Brickey, PhD, Neil.

Dysregulation of innate immune receptors on neutrophils in chronic granulomatous disease Dominik Hartl, MD, Natalie Lehmann, MD, Florian Hoffmann, MD,

Analysis of the lineage relationship between mast cells and basophils using the c-kit D816V mutation as a biologic signature Can N. Kocabas, MD, Akif.

Exosome-enclosed microRNAs in exhaled breath hold potential for biomarker discovery in patients with pulmonary diseases Anirban Sinha, MSc, Amit Kumar.

Human rhinovirus infection enhances airway epithelial cell production of growth factors involved in airway remodeling Richard Leigh, MBChB, PhD, Wale.

CCL17/thymus and activation-regulated chemokine induces calcitonin gene–related peptide in human airway epithelial cells through CCR4 Kandace Bonner,

Defective calcium signaling and disrupted CD20–B-cell receptor dissociation in patients with common variable immunodeficiency disorders Annick A.J.M.

Reply Journal of Allergy and Clinical Immunology

CD25 deficiency causes an immune dysregulation, polyendocrinopathy, enteropathy, X- linked–like syndrome, and defective IL-10 expression from CD4 lymphocytes

Cigarette smoke exposure is associated with vitamin D3 deficiencies in patients with chronic rhinosinusitis Jennifer K. Mulligan, PhD, Whitney Nagel,

Bleomycin hydrolase downregulation in lesional skin of adult atopic dermatitis patients is independent of FLG gene mutations Laurence Pellerin, PhD,

IgG4 production is confined to human IL-10–producing regulatory B cells that suppress antigen-specific immune responses Willem van de Veen, MSc, Barbara.

Karl J. Staples, PhD, Timothy S. C. Hinks, MB BS, Jon A

Anti-inflammatory and corticosteroid-enhancing actions of vitamin D in monocytes of patients with steroid-resistant and those with steroid-sensitive asthma

Pulmonary chemokines and their receptors differentiate children with asthma and chronic cough Dominik Hartl, MD, Matthias Griese, MD, Thomas Nicolai,

IL-31 is associated with cutaneous lymphocyte antigen–positive skin homing T cells in patients with atopic dermatitis Janine Bilsborough, PhD, Donald.

Statins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase

Effect of codeine on objective measurement of cough in chronic obstructive pulmonary disease Jaclyn Smith, MD, PhD, Emily Owen, MPhil, John Earis, MD,

Natural history of cow’s milk allergy

Presentation transcript:

Pulmonary sarcoidosis is associated with exosomal vitamin D–binding protein and inflammatory molecules Maria-Jose Martinez-Bravo, PhD, Casper J.E. Wahlund, MSc, Khaleda Rahman Qazi, PhD, Robert Moulder, PhD, Ana Lukic, MSc, Olof Rådmark, PhD, Riitta Lahesmaa, PhD, Johan Grunewald, MD, PhD, Anders Eklund, MD, PhD, Susanne Gabrielsson, PhD Journal of Allergy and Clinical Immunology Volume 139, Issue 4, Pages 1186-1194 (April 2017) DOI: 10.1016/j.jaci.2016.05.051 Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Protein profiles of BALF exosomes captured by anti–MHC class II–coated latex beads and analyzed by using flow cytometry. A and B, Exosome markers tetraspanin CD63 and CD9. C and D, Expression of HLA-DR and CD54 on exosomes. MFI, Mean fluorescence intensity normalized to isotype controls. Open circles indicate patients with Löfgren syndrome, and solid circles represent patients with chronic sarcoidosis. **P < .01, Mann-Whitney or Kruskal-Wallis test (the latter for patients with Löfgren syndrome/patients with non-Löfgren disorders/healthy subjects). Journal of Allergy and Clinical Immunology 2017 139, 1186-1194DOI: (10.1016/j.jaci.2016.05.051) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Summary of the biological processes affected in BALF exosomes from patients with sarcoidosis compared with those from healthy control subjects, as measured by using iTRAQ. DAVID, a functional annotation clustering tool, was used to group related biological processes. Annotation clusters with an upregulated and downregulated expression score of greater than 2 are shown. Journal of Allergy and Clinical Immunology 2017 139, 1186-1194DOI: (10.1016/j.jaci.2016.05.051) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Activating and inhibiting proteins involved in the complement cascade show a different profile in BALF exosomes from patients with sarcoidosis and healthy control subjects, as measured by using iTRAQ. Abundance of proteins is related to the internal control. Bars represent relative linear protein abundance in patients with sarcoidosis and healthy control subjects. Journal of Allergy and Clinical Immunology 2017 139, 1186-1194DOI: (10.1016/j.jaci.2016.05.051) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 CD55 levels are lower in BALF exosomes from patients than in those from healthy control subjects, as measured by using iTRAQ and flow cytometry. A, Relative abundance of CD55 compared with a pooled reference, as measured by using iTRAQ in patients with sarcoidosis and healthy control subjects. B, CD55 levels on exosomes bound to anti-CD63–coated beads and measured by using flow cytometry adjusted to isotype-matched control. Open circles indicate patients with Löfgren syndrome, and solid circles indicate patients with chronic sarcoidosis. **P < .01, Mann-Whitney or Kruskal-Wallis test (the latter for patients with Löfgren syndrome/patients with non-Löfgren disorders/healthy subjects). Journal of Allergy and Clinical Immunology 2017 139, 1186-1194DOI: (10.1016/j.jaci.2016.05.051) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 BALF exosomes from patients carry more complement C3 than those of healthy control subjects. A, Relative abundance of C3 compared with an internal pooled reference measured by using iTRAQ in patients with sarcoidosis and healthy control subjects. B, C3 levels on exosomes bound to CD63-coated beads and measured by using flow cytometry adjusted to isotype-matched controls. C, Western Blot analysis of C3 in protein isolates from BALF exosomes of patients with sarcoidosis (P1-P6) and healthy control subjects (H1-H5). Before transfer, the gel was scanned for total protein contents; relative intensities correlating with protein amounts are plotted in percentage of the strongest sample. MW, Molecular weight marker. Open circles indicate patients with Löfgren syndrome, and solid circles indicate patients with chronic sarcoidosis. **P < .01, Mann-Whitney or Kruskal-Wallis test (the latter for patients with Löfgren syndrome/patients with non-Löfgren disorders/healthy subjects). Journal of Allergy and Clinical Immunology 2017 139, 1186-1194DOI: (10.1016/j.jaci.2016.05.051) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 BALF exosomes carry LT pathway enzymes. A, LTA4H in BALF exosomes detected by using iTRAQ in patients with sarcoidosis and healthy subjects. Open circles indicate patients with Löfgren syndrome, and solid circles indicate patients with chronic sarcoidosis. B, Western blot analysis of 5-LO and LTA4H in patients (S) and healthy control subjects (H). C, Quantitative analysis of LTA4H Western blot band intensities. *P < .05, Mann-Whitney or Kruskal-Wallis test (the latter for patients with Löfgren syndrome/patients with non-Löfgren disorders/healthy subjects). Journal of Allergy and Clinical Immunology 2017 139, 1186-1194DOI: (10.1016/j.jaci.2016.05.051) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 7 VDBP is present on exosomes and is enriched in patients compared with healthy control subjects. A, Relative abundance of VDBP on BALF exosomes, as detected by using iTRAQ relative to a pooled reference. B, VDBP on BALF exosomes from healthy control subjects and patients with sarcoidosis, as measured by using ELISA. In the sarcoidosis group open circles indicate patients with Löfgren syndrome, and solid circles indicate patients with chronic disease. C, VDBP measured in plasma of patients and healthy control subjects by using ELISA. D, VDBP levels on exosomes isolated from plasma, as measured by using ELISA. *P < .05 and **P < .01, Mann-Whitney or Kruskal-Wallis test (the latter for patients with Löfgren syndrome/patients with non-Löfgren disorders/healthy subjects). Journal of Allergy and Clinical Immunology 2017 139, 1186-1194DOI: (10.1016/j.jaci.2016.05.051) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions