Joris M. van Montfrans, MD, PhD, Andy I. M

Slides:



Advertisements
Similar presentations
Isaac J. Nijman, PhD, Joris M
Advertisements

Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy  Erik Wambre, PhD, Jonathan.
Specific immunotherapy modifies allergen-specific CD4+ T-cell responses in an epitope- dependent manner  Erik Wambre, PhD, Jonathan H. DeLong, BSc, Eddie.
Barbara Stanic, PhD, Willem van de Veen, PhD, Oliver F
Defective calcium signaling and disrupted CD20–B-cell receptor dissociation in patients with common variable immunodeficiency disorders  Annick A.J.M.
Expression of IL-9 receptor α chain on human germinal center B cells modulates IgE secretion  Lama M. Fawaz, PhD, Ehssan Sharif-Askari, PhD, Oumnia Hajoui,
Flow cytometry imaging identifies rare TH2 cells expressing thymic stromal lymphopoietin receptor in a “proallergic” milieu  Amanda J. Reefer, MS, Kathryn.
Combined immunodeficiency due to JAK3 mutation in a child presenting with skin granuloma  Alessia Scarselli, MD, Silvia Di Cesare, BSc, Gigliola Di Matteo,
Homozygous N-terminal missense mutation in TRNT1 leads to progressive B-cell immunodeficiency in adulthood  Glynis Frans, MPharm, Leen Moens, PhD, Heidi.
Human circulating group 2 innate lymphoid cells can express CD154 and promote IgE production  Laura Maggi, PhD, Gianni Montaini, BSc, Alessio Mazzoni,
Correlation of allergen-specific T follicular helper cell counts with specific IgE levels and efficacy of allergen immunotherapy  Yin Yao, MD, Cai-Ling.
Reduced TH1/TH17 CD4 T-cell numbers are associated with impaired purified protein derivative–specific cytokine responses in patients with HIV-1 infection 
William A. Comrie, PhD, Aiman J
A novel mutation in CD132 causes X-CID with defective T-cell activation and impaired humoral reactivity  Taco W. Kuijpers, MD, PhD, Paul A. Baars, PhD,
MiR-155 is overexpressed in patients with atopic dermatitis and modulates T-cell proliferative responses by targeting cytotoxic T lymphocyte–associated.
Human B cells promote T-cell plasticity to optimize antibody response by inducing coexpression of TH1/TFH signatures  Jelle de Wit, PhD, Tineke Jorritsma,
Human CD19 and CD40L deficiencies impair antibody selection and differentially affect somatic hypermutation  Menno C. van Zelm, PhD, Sophinus J.W. Bartol,
Toll-like receptor 7–induced naive human B-cell differentiation and immunoglobulin production  Mark C. Glaum, MD, PhD, Shilpi Narula, MD, Decheng Song,
Magdalena A. Berkowska, PhD, Jorn J
Analysis of somatic hypermutations in the IgM switch region in human B cells  Katsuyuki Horiuchi, MD, PhD, Kohsuke Imai, MD, PhD, Kanako Mitsui-Sekinaka,
Type 3 innate lymphoid cells induce proliferation of CD94+ natural killer cells  Shuo Li, PhD, Hideaki Morita, MD, PhD, Beate Rückert, Sci Tec, Tadech.
Jelle de Wit, PhD, Maarten E. Emmelot, BSc, Martien C. M
Molecular mechanisms of functional natural killer deficiency in patients with partial DiGeorge syndrome  Peilin Zheng, PhD, Lenora M. Noroski, MD, Imelda.
Recurrent viral infections associated with a homozygous CORO1A mutation that disrupts oligomerization and cytoskeletal association  Christina S. Yee,
Jeff Choi, BSc, Rosemary Fernandez, PhD, Holden T
Inflammation in common variable immunodeficiency is associated with a distinct CD8+ response to cytomegalovirus  Sayed Mahdi Marashi, PhD, Mohammad Raeiszadeh,
Mutation in IRF2BP2 is responsible for a familial form of common variable immunodeficiency disorder  Michael D. Keller, MD, Rahul Pandey, PhD, Dong Li,
Modification of cellular and humoral immunity by somatically reverted T cells in X-linked lymphoproliferative syndrome type 1  Akihiro Hoshino, MD, PhD,
Jug r 2–reactive CD4+ T cells have a dominant immune role in walnut allergy  Luis Diego Archila, MSc, David Jeong, MD, Mariona Pascal, PhD, Joan Bartra,
Kathleen R. Bartemes, BA, Gail M. Kephart, BS, Stephanie J
T-cell receptor diversity is selectively skewed in T-cell populations of patients with Wiskott-Aldrich syndrome  Junfeng Wu, MD, Dawei Liu, MS, Wenwei.
CD94/NKG2C is a killer effector molecule in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis  Esther Morel, PhD, Salvador Escamochero,
A novel Rab27a mutation binds melanophilin, but not Munc13-4, causing immunodeficiency without albinism  Petra Netter, PhD, Sanny K. Chan, MD, PhD, Pinaki.
Inhibition of human B-cell development into plasmablasts by histone deacetylase inhibitor valproic acid  Anne-Kathrin Kienzler, MSc, Marta Rizzi, MD,
Defective B-cell memory in patients with Down syndrome
Targeting allergen to FcγRI reveals a novel TH2 regulatory pathway linked to thymic stromal lymphopoietin receptor  Kathryn E. Hulse, PhD, Amanda J. Reefer,
Fibronectin is a TH1-specific molecule in human subjects
De novo oligoclonal expansions of circulating plasmablasts in active and relapsing IgG4- related disease  Hamid Mattoo, PhD, Vinay S. Mahajan, MBBS, PhD,
Patients with atopic dermatitis and history of eczema herpeticum elicit herpes simplex virus–specific type 2 immune responses  Stephan Traidl, Petra Kienlin,
Specific immunotherapy modifies allergen-specific CD4+ T-cell responses in an epitope- dependent manner  Erik Wambre, PhD, Jonathan H. DeLong, BSc, Eddie.
Chronic cat allergen exposure induces a TH2 cell–dependent IgG4 response related to low sensitization  Amedee Renand, PhD, Luis D. Archila, MSc, John.
Impaired natural killer cell functions in patients with signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations  Giovanna.
Brent E. Palmer, PhD, Douglas G. Mack, PhD, Allison K
A novel LPS-responsive beige-like anchor protein (LRBA) mutation presents with normal cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and overactive.
Bet v 1–specific T-cell receptor/forkhead box protein 3 transgenic T cells suppress Bet v 1–specific T-cell effector function in an activation-dependent.
Novel mutation in STXBP2 prevents IL-2–induced natural killer cell cytotoxicity  Rushani W. Saltzman, MD, Linda Monaco-Shawver, BA, Kejian Zhang, MD, MBA,
Fibronectin is a TH1-specific molecule in human subjects
Human CD20+CD43+CD27+CD5− B cells generate antibodies to capsular polysaccharides of Streptococcus pneumoniae  Bert Verbinnen, PhD, Kris Covens, PhD,
Expression of IL-9 receptor α chain on human germinal center B cells modulates IgE secretion  Lama M. Fawaz, PhD, Ehssan Sharif-Askari, PhD, Oumnia Hajoui,
Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy  Erik Wambre, PhD, Jonathan.
Exaggerated follicular helper T-cell responses in patients with LRBA deficiency caused by failure of CTLA4-mediated regulation  Fayhan J. Alroqi, MD,
Defective actin accumulation impairs human natural killer cell function in patients with dedicator of cytokinesis 8 deficiency  Melissa C. Mizesko, MD,
Direct ex vivo analysis of allergen-specific CD4+ T cells
Amplification of Toll-like receptor–mediated signaling through spleen tyrosine kinase in human B-cell activation  Shigeru Iwata, MD, PhD, Kunihiro Yamaoka,
A novel hypomorphic mutation in STIM1 results in a late-onset immunodeficiency  Heidi Schaballie, MD, Rémy Rodriguez, MS, Emmanuel Martin, PhD, Leen Moens,
Persistence of natural killer cells with expansion of a hypofunctional CD56−CD16+KIR+NKG2C+ subset in a patient with atypical Janus kinase 3–deficient.
Matthew J. Loza, PhD, Susan Foster, PhD, Stephen P
Influence of cytomegalovirus infection on immune cell phenotypes in patients with common variable immunodeficiency  Sayed Mahdi Marashi, PhD, Mohammed.
Eosinophilic gastrointestinal disease and peanut allergy are alternatively associated with IL-5+ and IL-5− TH2 responses  Calman Prussin, MD, Joohee Lee,
Deficiency of caspase recruitment domain family, member 11 (CARD11), causes profound combined immunodeficiency in human subjects  Polina Stepensky, MD,
Katie Frith, MD, Anne-Laure Joly, PhD, Cindy S. Ma, PhD, Stuart G
Defective calcium signaling and disrupted CD20–B-cell receptor dissociation in patients with common variable immunodeficiency disorders  Annick A.J.M.
IL-10–producing monocytes differentiate to alternatively activated macrophages and are increased in atopic patients  Antje Prasse, MD, Martin Germann,
Severe cutaneous human papillomavirus infection associated with natural killer cell deficiency following stem cell transplantation for severe combined.
IgG4 production is confined to human IL-10–producing regulatory B cells that suppress antigen-specific immune responses  Willem van de Veen, MSc, Barbara.
Early-onset inflammatory bowel disease and common variable immunodeficiency–like disease caused by IL-21 deficiency  Elisabeth Salzer, MD, Aydan Kansu,
Intact IL-12 signaling is necessary for the generation of human natural killer cells with enhanced effector function after restimulation  Venkateswara.
Perturbations of natural killer cell regulatory functions in respiratory allergic diseases  Francesca Scordamaglia, MD, Mirna Balsamo, PhD, Antonio Scordamaglia,
Invariant natural killer T cells from children with versus without food allergy exhibit differential responsiveness to milk-derived sphingomyelin  Soma.
Der p 1–induced CD4+FOXP3+GATA3+ T cells have suppressive properties and contribute to the polarization of the TH2-associated response  Lieke Reubsaet,
Presentation transcript:

CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia  Joris M. van Montfrans, MD, PhD, Andy I.M. Hoepelman, MD, PhD, Sigrid Otto, BSc, Marielle van Gijn, PhD, Lisette van de Corput, PhD, Roel A. de Weger, PhD, Linda Monaco-Shawver, BSc, Pinaki P. Banerjee, PhD, Elisabeth A.M. Sanders, MD, PhD, Cornelia M. Jol–van der Zijde, PhD, Michael R. Betts, PhD, Jordan S. Orange, MD, PhD, Andries C. Bloem, PhD, Kiki Tesselaar, PhD  Journal of Allergy and Clinical Immunology  Volume 129, Issue 3, Pages 787-793.e6 (March 2012) DOI: 10.1016/j.jaci.2011.11.013 Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Absence of CD27 expression because of a nonsense mutation in the CD27 gene. A, Family pedigree (/, deceased persons; double lining, consanguinity). B, FACS analysis of CD27 membrane expression on PBMCs. C, Sequence analysis of the CD27 gene. The mutation (boldface) identified in both patients in exon 1 results in a premature stop codon (X) in the signal peptide of the protein (NP_001233.1), as depicted in the protein sequence (superimposed on the gene sequence). Journal of Allergy and Clinical Immunology 2012 129, 787-793.e6DOI: (10.1016/j.jaci.2011.11.013) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Phenotypic analysis of the index patient’s B cells. A, The presence of different B-cell subsets was analyzed by using FACS. Within the CD19+ B cells, the fraction of naive (IgM+ and IgD+) or memory (IgA+ or IgG+) B cells was determined. B, The presence of GCs was determined by staining tissue sections with anti-CD79a and anti-CD23 mAb. IF, Interfollicular area; MZ, mantle zone. Journal of Allergy and Clinical Immunology 2012 129, 787-793.e6DOI: (10.1016/j.jaci.2011.11.013) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Functional analysis of the index patient’s B cells. A, PBMCs were tested for their capacity to differentiate into plasmablasts after T cell–independent (TI; SAC/IL2) or T cell–dependent (TD; PWM) stimulation. The fraction of plasmablasts was determined based on morphology and intracellular immunoglobulin staining on day 7. O, Index patient; -, control subjects. B, Vaccination response of the index patient to polysaccharide vaccine (Pneumovax 23) and conjugated polysaccharide Men C vaccine (NeissVac). C, Vaccination response of the index patient to protein antigen (diploid cell rabies vaccine). The mean of healthy control subjects (black line) with 95% CIs (gray region) is shown. Journal of Allergy and Clinical Immunology 2012 129, 787-793.e6DOI: (10.1016/j.jaci.2011.11.013) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Analysis of the index patient’s NK cells. A, Cytotoxic activity of highly enriched, negatively selected ex vivo PBMC NK cells against the indicated targets. B, Antibody-dependent cellular cytotoxicity of Raji cells induced by the addition of rituximab relative to added control IgG. Journal of Allergy and Clinical Immunology 2012 129, 787-793.e6DOI: (10.1016/j.jaci.2011.11.013) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Analysis of the index patient’s T cells. A, Proliferation assays with PBMCs or CD4+ T cells and the indicated stimuli. Results are presented as the stimulation index (index patient cpm/healthy control subject cpm). B, Subset analysis of T cells32 in PBMCs by means of FACS. Within CD8+CD3+ T cells, the fractions of naive (CCR7+CD45RO−), central memory (CCR7+CD45RO+), effector memory (CCR7−CD45RO+), and effector (CCR7−CD45RO+) cells were determined. C, Intracellular accumulation of IL-2 and IFN-γ in EBV-specific CD3+CD8+ T cells after stimulation with HLA-A2–restricted EBV peptide pools. Journal of Allergy and Clinical Immunology 2012 129, 787-793.e6DOI: (10.1016/j.jaci.2011.11.013) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Longitudinal analysis of the index patient’s cell numbers, immunoglobulin numbers, and EBV plasma load over time. In the index patient, cell numbers and immunoglobulin levels (A) and EBV plasma load (B; solid circles, no detectable load; arrows, indicated load) were determinedE1 at the indicated time points (symbols) between 1989 and 1995 (Fig E1, A) and 2000 and 2008 (Fig E1, B), respectively. Journal of Allergy and Clinical Immunology 2012 129, 787-793.e6DOI: (10.1016/j.jaci.2011.11.013) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 NK cell subset analysis demonstrates appropriate developmental and functional NK cell populations in the index patient’s PBMCs. Evaluation of the NK cell subsets in the patient’s (A and C) and control subjects’ (B and D) PBMCs demonstrating populations present among total (CD56+CD3−; Fig E2, A and B) and CD56bright (CD56++CD3−; Fig E2, C and D) NK cells. Arrows depict the gating strategy starting at the side scatter/forward scatter plot. Journal of Allergy and Clinical Immunology 2012 129, 787-793.e6DOI: (10.1016/j.jaci.2011.11.013) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Absence of costimulation through the CD27 ligand CD70 of the index patient’s T cells. Purified CD4+ T cells from the index patient and 2 healthy control subjects were stimulated with PHA and mock transfectants (black bar), CD70 transfectants (gray bar), or CD70 transfectants and blocking CD70 mAb. Proliferation was measured based on tritiated thymidine incorporation and is depicted as the stimulation index (ratio [median cpm situation X]/median cpm + P815). Journal of Allergy and Clinical Immunology 2012 129, 787-793.e6DOI: (10.1016/j.jaci.2011.11.013) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Presence of polyfunctional EBV-specific T cells in the index patient. PBMCs were stimulated, and functional profiles were measured. The pie plots depict the fraction of penta (red), tetra (blue), tri (green), bi (orange), and mono (yellow) functional cells of the CD8+ T cells. The bar graphs represent the relative proportion of the CD8+ T cells having the indicated functions after the different stimulations.E2 MIP1a, Macrophage inflammatory protein 1α; SEB, staphylococcal enterotoxin B. Journal of Allergy and Clinical Immunology 2012 129, 787-793.e6DOI: (10.1016/j.jaci.2011.11.013) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions