Bart O Roep

Summary

Affiliation: Leiden University Medical Center
Country: The Netherlands

Publications

  1. ncbi request reprint Cross-reactive mycobacterial and self hsp60 epitope recognition in I-A(g7) expressing NOD, NOD-asp and Biozzi AB/H mice
    Astrid G S van Halteren
    Department of Immunohematology and Blood Transfusion, Leids Universitair Medisch Centrum, The Netherlands
    J Autoimmun 18:139-47. 2002
  2. pmc Simultaneous detection of circulating autoreactive CD8+ T-cells specific for different islet cell-associated epitopes using combinatorial MHC multimers
    Jurjen H Velthuis
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Diabetes 59:1721-30. 2010
  3. doi request reprint Diabetogenic T lymphocytes in human Type 1 diabetes
    Bart O Roep
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands
    Curr Opin Immunol 23:746-53. 2011
  4. ncbi request reprint Modulation of autoimmunity to beta-cell antigens by proteases
    B O Roep
    Department of Immunohaematology and Blood Transfusion, Leiden University Medical Centre, The Netherlands
    Diabetologia 45:686-92. 2002
  5. ncbi request reprint Are insights gained from NOD mice sufficient to guide clinical translation? Another inconvenient truth
    Bart O Roep
    Department of Immunohaematology and Blood Transfusion, E3 Q, LUMC, P O Box 9600, NL 2300 RC Leiden, The Netherlands
    Ann N Y Acad Sci 1103:1-10. 2007
  6. ncbi request reprint The role of T-cells in the pathogenesis of Type 1 diabetes: from cause to cure
    Bart O Roep
    Dept Immunohaematology and Blood Transfusion, E3 Q, Leiden University Medical Center, P O Box 9600, 2300 RC Leiden, The Netherlands
    Diabetologia 46:305-21. 2003
  7. ncbi request reprint Molecular mimicry in autoimmune neurological disease after viral infection
    Bart O Roep
    Department Immunoheamtology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Curr Med Chem 10:1939-43. 2003
  8. ncbi request reprint Surrogate end points in the design of immunotherapy trials: emerging lessons from type 1 diabetes
    Bart O Roep
    Leiden University Medical Center, National Diabetes Expert Center, Leiden, The Netherlands
    Nat Rev Immunol 10:145-52. 2010
  9. ncbi request reprint Islet autoreactive CD8 T-cells in type 1 diabetes: licensed to kill?
    Bart O Roep
    Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Diabetes 57:1156. 2008
  10. ncbi request reprint Animal models have little to teach us about type 1 diabetes: 1. In support of this proposal
    B O Roep
    Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, E3 Q, PO Box 9600, 2300 RC, Leiden, The Netherlands
    Diabetologia 47:1650-6. 2004

Detail Information

Publications112 found, 100 shown here

  1. ncbi request reprint Cross-reactive mycobacterial and self hsp60 epitope recognition in I-A(g7) expressing NOD, NOD-asp and Biozzi AB/H mice
    Astrid G S van Halteren
    Department of Immunohematology and Blood Transfusion, Leids Universitair Medisch Centrum, The Netherlands
    J Autoimmun 18:139-47. 2002
    ..Yet, proliferation of hsp60 autoreactive T cells is solely measured in combination with insulitis and as such serves as a surrogate marker for islet inflammation...
  2. pmc Simultaneous detection of circulating autoreactive CD8+ T-cells specific for different islet cell-associated epitopes using combinatorial MHC multimers
    Jurjen H Velthuis
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Diabetes 59:1721-30. 2010
    ..Yet, conventional detection techniques (ELISPOT and HLA tetramers) require many cells and are relatively insensitive...
  3. doi request reprint Diabetogenic T lymphocytes in human Type 1 diabetes
    Bart O Roep
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands
    Curr Opin Immunol 23:746-53. 2011
    ..For these reasons, this review will focus on the role of diabetogenic T lymphocytes in this disease-defining event...
  4. ncbi request reprint Modulation of autoimmunity to beta-cell antigens by proteases
    B O Roep
    Department of Immunohaematology and Blood Transfusion, Leiden University Medical Centre, The Netherlands
    Diabetologia 45:686-92. 2002
    ..Proteases are used in therapy for autoimmune diseases yet the mechanism of their action remains to be determined. We studied the immunological basis of protease therapy in the context of Type I (insulin-dependent) diabetes mellitus...
  5. ncbi request reprint Are insights gained from NOD mice sufficient to guide clinical translation? Another inconvenient truth
    Bart O Roep
    Department of Immunohaematology and Blood Transfusion, E3 Q, LUMC, P O Box 9600, NL 2300 RC Leiden, The Netherlands
    Ann N Y Acad Sci 1103:1-10. 2007
    ..I will argue that animal models have limited but evident value when it comes to teaching us about type 1 diabetes in humans, and we can take advantage of this value more efficiently...
  6. ncbi request reprint The role of T-cells in the pathogenesis of Type 1 diabetes: from cause to cure
    Bart O Roep
    Dept Immunohaematology and Blood Transfusion, E3 Q, Leiden University Medical Center, P O Box 9600, 2300 RC Leiden, The Netherlands
    Diabetologia 46:305-21. 2003
    ....
  7. ncbi request reprint Molecular mimicry in autoimmune neurological disease after viral infection
    Bart O Roep
    Department Immunoheamtology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Curr Med Chem 10:1939-43. 2003
    ..Subsequent microarray studies unequivocally demonstrated functional mimicry of seemingly disparate amino acid sequences. This review summarises the present evidence for molecular mimicry in neurological autoimmune diseases and virus..
  8. ncbi request reprint Surrogate end points in the design of immunotherapy trials: emerging lessons from type 1 diabetes
    Bart O Roep
    Leiden University Medical Center, National Diabetes Expert Center, Leiden, The Netherlands
    Nat Rev Immunol 10:145-52. 2010
    ..In this Opinion article we offer a perspective on the future of clinical trial design in which the process is significantly shortened by making greater use of laboratory measures to determine therapeutic outcome...
  9. ncbi request reprint Islet autoreactive CD8 T-cells in type 1 diabetes: licensed to kill?
    Bart O Roep
    Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Diabetes 57:1156. 2008
  10. ncbi request reprint Animal models have little to teach us about type 1 diabetes: 1. In support of this proposal
    B O Roep
    Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, E3 Q, PO Box 9600, 2300 RC, Leiden, The Netherlands
    Diabetologia 47:1650-6. 2004
  11. ncbi request reprint Molecular mimicry in type 1 diabetes: immune cross-reactivity between islet autoantigen and human cytomegalovirus but not Coxsackie virus
    B O Roep
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Ann N Y Acad Sci 958:163-5. 2002
    ..However, T cell clones reactive with linear homologies previously described as putative candidates for T cell cross-reactivity between GAD65 and Coxsackie virus peptide were unable to recognize the homologous counterparts...
  12. doi request reprint Discovery of low-affinity preproinsulin epitopes and detection of autoreactive CD8 T-cells using combinatorial MHC multimers
    Wendy W Unger
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    J Autoimmun 37:151-9. 2011
    ....
  13. doi request reprint Transfer of regulatory properties from tolerogenic to proinflammatory dendritic cells via induced autoreactive regulatory T cells
    Fleur S Kleijwegt
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
    J Immunol 187:6357-64. 2011
    ..Our data indicated that human tolerogenic DCs confer infectious tolerance by inducing Ag-specific Tregs, which, in turn, re-educate proinflammatory mature DCs into DCs with regulatory properties...
  14. pmc Genetically engineered human islets protected from CD8-mediated autoimmune destruction in vivo
    Arnaud Zaldumbide
    Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands
    Mol Ther 21:1592-601. 2013
    ..Collectively, our data provide proof of concept that human β cells can be efficiently genetically modified to provide protection from killing mediated by autoreactive T cells and retain their function in vitro and in vivo. ..
  15. doi request reprint Pretransplantation GAD-autoantibody status to guide prophylactic antibody induction therapy in simultaneous pancreas and kidney transplantation
    Jan Ringers
    1 Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands 2 Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands 3 Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands 4 Department of Immunology of Diabetes Unit, San Raffaele Scientific Institute Milan, Italy 5 Center for Regenerative Therapies Dresden, Dresden, Germany 6 Address correspondence to Johan W de Fijter, M D, Ph D, Department of Nephrology, Leiden University Medical Center, C3 P22, P O Box 9600, NL 2300 RC Leiden, The Netherlands
    Transplantation 96:745-52. 2013
    ..We assessed the safety and efficacy of daclizumab or ATG prophylaxis in combination with triple immunotherapy in simultaneous pancreas-kidney transplant (SPKT) recipients...
  16. doi request reprint Tolerogenic dendritic cells impede priming of naïve CD8⁺ T cells and deplete memory CD8⁺ T cells
    Fleur S Kleijwegt
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Eur J Immunol 43:85-92. 2013
    ..Yet, Combi-DCs pulsed with CD8(+) T-cell epitopes also act as targets of cytotoxicity, which is undesirable for survival of Combi-DCs infused into patients in therapeutic immune intervention strategies...
  17. ncbi request reprint Elevated levels of mannose-binding lectin at clinical manifestation of type 1 diabetes in juveniles
    Lee H Bouwman
    Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
    Diabetes 54:3002-6. 2005
    ....
  18. pmc Type 1 diabetes-associated HLA-DQ8 transdimer accommodates a unique peptide repertoire
    Menno van Lummel
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    J Biol Chem 287:9514-24. 2012
    ..Our findings provide a molecular basis for the association between HLA-DQ transdimers and T1D and set the stage for rational testing of potential diabetogenic peptide epitopes...
  19. doi request reprint Induction of Treg by monocyte-derived DC modulated by vitamin D3 or dexamethasone: differential role for PD-L1
    Wendy W J Unger
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Eur J Immunol 39:3147-59. 2009
    ..Both are potentially useful to specifically down-regulate unwanted immune responses and induce immune tolerance. These modulated DC appear suitable as adjuvant in antigen-specific clinical vaccination intervention strategies...
  20. ncbi request reprint Alloreactivity against repeated HLA mismatches of sequential islet grafts transplanted in non-uremic type 1 diabetes patients
    Corine A van Kampen
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Transplantation 80:118-26. 2005
    ....
  21. ncbi request reprint 1alpha,25-dihydroxyvitamin D3 or analogue treated dendritic cells modulate human autoreactive T cells via the selective induction of apoptosis
    Astrid G S van Halteren
    Department of Immunohematology and Blood Transfusion, E3Q, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
    J Autoimmun 23:233-9. 2004
    ..Thus, in vitro preconditioning of DC with 1,25(OH)2D3 or analogue yields regulatory DC that may interfere with ongoing autoimmunity in vivo without affecting T cells with other specificities...
  22. ncbi request reprint Critical role for TNF in the induction of human antigen-specific regulatory T cells by tolerogenic dendritic cells
    Fleur S Kleijwegt
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, P O Box 9600, 2300 RC Leiden, The Netherlands
    J Immunol 185:1412-8. 2010
    ..Interaction between mTNF and TNFRII instructs the induction of suppressive Tregs by VD3-DCs. Anti-TNF therapy may therefore act adversely in different patients or disease pathways...
  23. pmc Cellular islet autoimmunity associates with clinical outcome of islet cell transplantation
    Volkert A L Huurman
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    PLoS ONE 3:e2435. 2008
    ..We tested the hypothesis that allograft rejection and recurrent autoimmunity contribute to this progressive loss of islet allograft function...
  24. doi request reprint Posttranslational modification of HLA-DQ binding islet autoantigens in type 1 diabetes
    Menno van Lummel
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Diabetes 63:237-47. 2014
    ..Most patients responded by interferon-γ, whereas most healthy donors produced interleukin-10 only. Thus, T-cell autoreactivity exists to modified islet epitopes that differs in quality and quantity between patients and healthy donors. ..
  25. ncbi request reprint Alternative splicing and differential expression of the islet autoantigen IGRP between pancreas and thymus contributes to immunogenicity of pancreatic islets but not diabetogenicity in humans
    V Martijn de Jong
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, E3 Q, P O Box 9600, NL2300RC, Leiden, The Netherlands
    Diabetologia 56:2651-8. 2013
    ..We tested whether specific splice variation in islets vs thymus correlates with loss of tolerance to IGRP in type 1 diabetes...
  26. pmc Autoreactive CD8 T cells associated with beta cell destruction in type 1 diabetes
    Gabrielle G M Pinkse
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands
    Proc Natl Acad Sci U S A 102:18425-30. 2005
    ..We demonstrate that CD8 T cell autoreactivity is associated with beta cell destruction in type 1 diabetes in humans...
  27. ncbi request reprint Therapy with the hsp60 peptide DiaPep277 in C-peptide positive type 1 diabetes patients
    Volkert A L Huurman
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Diabetes Metab Res Rev 23:269-75. 2007
    ..A randomized, double-blind, phase Ib/II study of peptide treatment was undertaken in recent onset type 1 diabetes patients with remaining insulin production...
  28. doi request reprint Clinical Dutch-English Lambert-Eaton Myasthenic syndrome (LEMS) tumor association prediction score accurately predicts small-cell lung cancer in the LEMS
    Maarten J Titulaer
    Leiden University Medical Center, Leiden, The Netherlands
    J Clin Oncol 29:902-8. 2011
    ..In view of its profound impact on therapy and survival, we developed and validated a score to identify the presence of SCLC early in the course of LEMS...
  29. ncbi request reprint Association analysis of myosin IXB and type 1 diabetes
    Stephan Persengiev
    Department Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Hum Immunol 71:598-601. 2010
    ..57). We conclude that MYO9B might not be a strong determinant of T1D, although there was some association in our initial Dutch study. Further studies are needed to evaluate the role of MYO9B in T1D...
  30. ncbi request reprint HLA class I epitope discovery in type 1 diabetes: independent and reproducible identification of proinsulin epitopes of CD8 T cells--report of the IDS T Cell Workshop Committee
    Gabrielle G M Pinkse
    Department of Immunohematology and Blood Transfusion, E3Q, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    Ann N Y Acad Sci 1079:19-23. 2006
    ..These studies imply that CD8 T cell-based HLA tetramers and ELISPOT analyses can be useful to monitor T1DM as well as islet transplantation, and may provide useful tools to assess immunological efficacy of immune intervention trials...
  31. ncbi request reprint Immune markers of disease and therapeutic intervention in type 1 diabetes
    Bart O Roep
    Department of Immunohaematology and Blood Transfusion, E3 Q, Leiden University Medical Center, PO Box 9600, NL 2300 RC Leiden, The Netherlands
    Novartis Found Symp 292:159-71; discussion 171-3, 202-3. 2008
    ..The challenge for the future is to determine which immune factors associate with tolerance to beta cell antigens, and to define what measures T cells can provide to suppress autoreactivity...
  32. ncbi request reprint Molecular mimicry in type 1 diabetes mellitus revisited: T-cell clones to GAD65 peptides with sequence homology to Coxsackie or proinsulin peptides do not crossreact with homologous counterpart
    N C Schloot
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Hum Immunol 62:299-309. 2001
    ..Yet, T-cell clones did not crossreact with linear sequence homologies, despite strong T-cell responses to individual peptides...
  33. pmc Cytomegalovirus in autoimmunity: T cell crossreactivity to viral antigen and autoantigen glutamic acid decarboxylase
    H S Hiemstra
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, P. O. Box 9600, NL-2300 RC Leiden, The Netherlands
    Proc Natl Acad Sci U S A 98:3988-91. 2001
    ..Thus, hCMV may be involved in the loss of T cell tolerance to autoantigen GAD65 by a mechanism of molecular mimicry leading to autoimmunity...
  34. ncbi request reprint Autoreactive T cell responses in insulin-dependent (Type 1) diabetes mellitus. Report of the first international workshop for standardization of T cell assays
    B O Roep
    Department of Immunohaematology and Blood Bank, Leiden University Medical Center, Leiden, The Netherlands
    J Autoimmun 13:267-82. 1999
    ....
  35. ncbi request reprint HLA-DR binding analysis of peptides from islet antigens in IDDM
    A Geluk
    Department of Immunohematology and Blood Bank, Leiden University Medical Center, The Netherlands
    Diabetes 47:1594-601. 1998
    ..Furthermore, negative thymic selection of insulin peptides in low-risk (HLA-DR2 expressing) subjects may explain the lack of autoreactivity to insulin in such individuals...
  36. ncbi request reprint Choice of antibody immunotherapy influences cytomegalovirus viremia in simultaneous pancreas-kidney transplant recipients
    Volkert A L Huurman
    Department of Surgery, Leiden University Medical Center, P O Box 9600, NL 2300 RC Leiden, Netherlands
    Diabetes Care 29:842-7. 2006
    ..In this study, we assessed the pattern of CMV viremia in SPK transplant recipients receiving either antithymocyte globulin (ATG) or anti-CD25 (daclizumab) immunosuppressive induction therapy...
  37. pmc Antigen targets of type 1 diabetes autoimmunity
    Bart O Roep
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 Leiden, The Netherlands
    Cold Spring Harb Perspect Med 2:a007781. 2012
    ..Here we will discuss recently gained insights into the identity, biology, structure, and presentation of islet antigens in relation to disease heterogeneity and β-cell destruction...
  38. doi request reprint Gluten-specific T cells cross-react between HLA-DQ8 and the HLA-DQ2α/DQ8β transdimer
    Yvonne Kooy-Winkelaar
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
    J Immunol 187:5123-9. 2011
    ..Because type 1 diabetes is strongly associated with the presence of HLA-DQ8trans, our findings may bear relevance to this disease as well...
  39. ncbi request reprint T-cell assays to determine disease activity and clinical efficacy of immune therapy in type 1 diabetes
    Pieter van de Linde
    Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
    Am J Ther 12:573-9. 2005
    ....
  40. ncbi request reprint Redirection of human autoreactive T-cells Upon interaction with dendritic cells modulated by TX527, an analog of 1,25 dihydroxyvitamin D(3)
    Astrid G S van Halteren
    Department of Immunohematology and Blood Transfusion, Leids Universitair Medisch Centrum, 2300 RC Leiden, The Netherlands
    Diabetes 51:2119-25. 2002
    ..Collectively, we provide evidence that nonhypercalcemic TX527 is a potent in vitro DC modulator, yielding DCs with the potential to change cytokine responses of committed autoreactive T-cells...
  41. ncbi request reprint Altered peptide ligands of islet autoantigen Imogen 38 inhibit antigen specific T cell reactivity in human type-1 diabetes
    A Geluk
    Department of Immunohematology and Blood Bank, Leiden University Medical Center, The Netherlands
    J Autoimmun 11:353-61. 1998
    ..Thus, the p55-70 APL inhibit beta cell autoantigen-induced activation of an Imogen-reactive T-cell clone derived from an IDDM patient, by acting as partial TCR agonists that inhibit TCR down-modulation...
  42. pmc Immunological efficacy of heat shock protein 60 peptide DiaPep277 therapy in clinical type I diabetes
    V A L Huurman
    Department of Immunohematology and Blood Transfusion, and Surgery, Leiden University Medical Center, Leiden, The Netherlands
    Clin Exp Immunol 152:488-97. 2008
    ..Declining or temporary proliferative responses to peptide DiaPep277 treatment may serve as an immunological biomarker for clinical efficacy...
  43. ncbi request reprint Mechanisms of antibody immunotherapy on clonal islet reactive T cells
    P van de Linde
    Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Hum Immunol 67:264-73. 2006
    ..ATG and the humanized monoclonal antibodies displayed contrasting mechanisms of action...
  44. doi request reprint Allograft-specific cytokine profiles associate with clinical outcome after islet cell transplantation
    V A L Huurman
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Am J Transplant 9:382-8. 2009
    ..Islet donor-specific IL10 production correlates with low alloreactivity and superior islet function...
  45. ncbi request reprint HLA and smoking in prediction and prognosis of small cell lung cancer in autoimmune Lambert-Eaton myasthenic syndrome
    Paul W Wirtz
    Department of Neurology, Leiden University Medical Center, P O Box 9600, 2300 RC Leiden, The Netherlands
    J Neuroimmunol 159:230-7. 2005
    ..Moreover, negativity for HLA-B8 combined with smoking behavior points more strongly to an underlying SCLC and predicts a worse prognosis in SCLC-LEMS patients...
  46. pmc Islet-specific CTL cloned from a type 1 diabetes patient cause beta-cell destruction after engraftment into HLA-A2 transgenic NOD/scid/IL2RG null mice
    Wendy W J Unger
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    PLoS ONE 7:e49213. 2012
    ....
  47. pmc Adenoviral vectors stimulate glucagon transcription in human mesenchymal stem cells expressing pancreatic transcription factors
    Arnaud Zaldumbide
    Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands
    PLoS ONE 7:e48093. 2012
    ..From these data we conclude that E1-deleted adenoviral vectors are not inert gene-transfer vectors and contribute to the modulation of the cellular differentiation pathways...
  48. doi request reprint The TRAF1-C5 region on chromosome 9q33 is associated with multiple autoimmune diseases
    Fina A S Kurreeman
    Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands
    Ann Rheum Dis 69:696-9. 2010
    ....
  49. ncbi request reprint Mannose-binding lectin: clinical implications for infection, transplantation, and autoimmunity
    Lee H Bouwman
    Department of Surgery, Leiden University Medical Center, P O Box 9600, 2300 RC Leiden, The Netherlands
    Hum Immunol 67:247-56. 2006
    ..This review provides a general outline of the genetic and molecular characteristics of MBL and discusses MBL-disease association and its consequence in infection, transplantation, and autoimmunity...
  50. doi request reprint Accumulation of autoreactive effector T cells and allo-specific regulatory T cells in the pancreas allograft of a type 1 diabetic recipient
    J H Velthuis
    Department of Immunohaematology and Blood Transfusion, Leiden University Medical Centre, P O Box 9600, 2300 RC, Leiden, The Netherlands
    Diabetologia 52:494-503. 2009
    ..We characterised infiltrating lymphocytes isolated from a pancreatic graft with normal endocrine function in a kidney-pancreas recipient with type 1 diabetes...
  51. ncbi request reprint Mannose binding lectin gene polymorphisms confer a major risk for severe infections after liver transplantation
    Lee H Bouwman
    Department of Surgery, Leiden University Medical Center, The Netherlands
    Gastroenterology 129:408-14. 2005
    ..The aims of our study were to establish the role of the liver in production of serum MBL and to evaluate the effect of MBL variant alleles on the susceptibility to infection after liver transplantation...
  52. ncbi request reprint Infectious tolerance as candidate therapy for type 1 diabetes: transfer of immunoregulatory properties from human regulatory T cells to other T cells and proinflammatory dendritic cells
    Fleur S Kleijwegt
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Crit Rev Immunol 33:415-34. 2013
    ....
  53. doi request reprint Preservation of recall immunity in anti-CD3-treated recent onset type 1 diabetes patients
    Gonnie M Alkemade
    Juvenile Diabetes Research Foundation Center for β Cell Therapy in Diabetes, Leiden, The Netherlands
    Diabetes Metab Res Rev 27:925-7. 2011
    ..The safety of any immune modulating agent in type 1 diabetes mellitus (T1DM) involves its selectivity on autoimmunity and its preservation of recall and tumour immunity...
  54. ncbi request reprint Autoreactive T cells in endocrine/organ-specific autoimmunity: why has progress been so slow?
    Bart O Roep
    Department of Immunohaematology and Blood Transfusion, E3 Q, Leiden University Medical Center, Albinusdreef 2, P O Box 9600, 2300 RC Leiden, The Netherlands
    Springer Semin Immunopathol 24:261-71. 2002
    ....
  55. ncbi request reprint HLA class I and II in Lambert-Eaton myasthenic syndrome without associated tumor
    P W Wirtz
    Department of Neurology, Leiden University Medical Center, The Netherlands
    Hum Immunol 62:809-13. 2001
    ..e. HLA-DR3 and -DQ2). HLA-B8+ patients had significantly younger age at onset of LEMS and tended to be female. This study shows that HLA-class I haplotype is associated with a distinct phenotype in NT-LEMS...
  56. ncbi request reprint T cell reactivity to heat shock protein 60 in diabetes-susceptible and genetically protected nonobese diabetic mice is associated with a protective cytokine profile
    A G van Halteren
    Department of Cell Biology and Immunology, Medical Faculty, Vrije Universiteit Amsterdam, Amsterdam
    J Immunol 165:5544-51. 2000
    ..Moreover, the capacity to respond to (self) hsp60 is independent of the MHC class II-associated genetic predisposition to diabetes...
  57. pmc Differential inhibition of autoreactive memory- and alloreactive naive T cell responses by soluble cytotoxic T lymphocyte antigen 4 (sCTLA4), CTLA4Ig and LEA29Y
    V A L Huurman
    Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
    Clin Exp Immunol 150:487-93. 2007
    ..Our results indicate a differential role for sCTLA4, CTLA4Ig and LEA29Y proteins in memory versus primary immune responses with implications for efficacy in intervention therapy...
  58. ncbi request reprint Elevated IL-16 levels in patients with systemic lupus erythematosus are associated with disease severity but not with genetic susceptibility to lupus
    L R Lard
    Department of Rheumatology, Leiden University Medical Centre, The Netherlands
    Lupus 11:181-5. 2002
    ..In conclusion, these results implicate an association of IL-16 with SLE...
  59. pmc Islet inflammation and CXCL10 in recent-onset type 1 diabetes
    B O Roep
    Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Clin Exp Immunol 159:338-43. 2010
    ..We demonstrate further pro- and anti-inflammatory islet autoreactivity, indicating that different adaptive and innate immune responses may contribute to insulitis and beta cell destruction...
  60. ncbi request reprint Functional genetic polymorphisms in cytokines and metabolic genes as additional genetic markers for susceptibility to develop type 1 diabetes
    P Eerligh
    Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Genes Immun 5:36-40. 2004
    ..The consequences of the increased transmission of a low Th2 expressing genotypes together with a normal Th1 profile may result in a net proinflammatory cytokine expression pattern...
  61. pmc Relevance of cytotoxic alloreactivity under different immunosuppressive regimens in clinical islet cell transplantation
    D L Roelen
    Department of Immunohaematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands
    Clin Exp Immunol 156:141-8. 2009
    ..This observational study demonstrates the usefulness of monitoring T cell reactivity against islet allografts to correlate immune function with graft survival...
  62. ncbi request reprint [Transplantation of the islets of Langerhans in patients with diabetes mellitus type 1]
    O T Terpstra
    afd Heelkunde, Leids Universitair Medisch Centrum, Postbus 9600, 2300 RC Leiden
    Ned Tijdschr Geneeskd 149:12-6. 2005
    ..Alternatives to pancreas donation, be it post-mortem or from a living donor, could be: sources for islets are xenotransplantation with the aid of pig islets and beta-cell neogenesis from embryonic stem cells or pancreatic duct cells...
  63. ncbi request reprint Human clonal CD8 autoreactivity to an IGRP islet epitope shared between mice and men
    W W J Unger
    Department of Immunohematology and Blood Transfusion, LUMC, E3 Q, P O Box 9600, 2300 RC Leiden, The Netherlands
    Ann N Y Acad Sci 1103:192-5. 2007
    ..We isolated a human CD8 T cell clone against this epitope, which confirms that this IGRP epitope is shared across species...
  64. ncbi request reprint [Indications for a favourable effect of intensive insulin therapy for newly-diagnosed type 2 diabetes]
    B O Roep
    Leids Universitair Medisch Centrum, Postbus 9600, 2300 RC Leiden
    Ned Tijdschr Geneeskd 152:2378-80. 2008
    ..These interesting findings need confirmation, notably in caucasoid populations, before guidelines for treatment of patients with type 2 diabetes can be changed...
  65. ncbi request reprint Strong association of MuSK antibody-positive myasthenia gravis and HLA-DR14-DQ5
    E H Niks
    Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
    Neurology 66:1772-4. 2006
    ..0 x 10(-8)). This association between MuSK Ab+ MG and a relatively rare HLA haplotype differs from the previously described association of early-onset acetylcholine receptor Ab+ MG with HLA-B8-DR3...
  66. ncbi request reprint HLA-DQ polymorphism and degree of heteroplasmy of the A3243G mitochondrial DNA mutation in maternally inherited diabetes and deafness
    E H van Essen
    Department of Metabolic Diseases and Endocrinology, Leiden University Medical Centre, The Netherlands
    Diabet Med 17:841-7. 2000
    ..Phenotypic expression of MIDD includes Type 1-like and Type 2-like diabetes. This study examined whether HLA-DQ phenotype and the degree of heteroplasmy in leucocyte and oral mucosa DNA influence clinical expression of the 3242 mutation...
  67. pmc Selective unresponsiveness to beta cell autoantigens after induction immunosuppression in pancreas transplantation with anti-interleukin-2 receptor antibody versus anti-thymocyte globulin
    P van de Linde
    Department of Surgery, LUMC, Leiden, The Netherlands
    Clin Exp Immunol 149:56-62. 2007
    ..The autoimmunity is affected effectively after daclizumab induction, while memory responses towards bacterial, viral and tumour antigens are preserved...
  68. ncbi request reprint HLA incompatibility and immunogenicity of human pancreatic islet preparations cocultured with blood cells of healthy donors
    Lee H Bouwman
    Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
    Hum Immunol 66:494-500. 2005
    ..Our results identify the potential immunogenicity of islet preparations transplanted between HLA-DR incompatible subjects regardless of an autoimmune background of the recipient...
  69. doi request reprint Changing faces, unmasking the beta-cell: post-translational modification of antigens in type 1 diabetes
    Menno van Lummel
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Curr Opin Endocrinol Diabetes Obes 20:299-306. 2013
    ..Description on post-translational modification of islet-autoantigens in type 1 diabetes (T1D)...
  70. ncbi request reprint [Immunotherapy for type 1 diabetes mellitus (DM1)]
    Cornelis R van der Torren
    Leids Universitair Medisch Centrum, afd Immunohaematologie and Bloedtransfusie, Leiden, The Netherlands
    Ned Tijdschr Geneeskd 156:A4268. 2012
    ..Discussion on the acceptability of the side effects of immunotherapy is desirable...
  71. ncbi request reprint Protection against anti-citrullinated protein antibody-positive rheumatoid arthritis is predominantly associated with HLA-DRB1*1301: a meta-analysis of HLA-DRB1 associations with anti-citrullinated protein antibody-positive and anti-citrullinated protein
    Diane Van der Woude
    Leiden University Medical Center, Leiden, The Netherlands
    Arthritis Rheum 62:1236-45. 2010
    ..The aim of this study was to perform a meta-analysis of 4 European populations to investigate which HLA-DRB1 alleles are associated with protection in anti-citrullinated protein antibody (ACPA)-positive RA and ACPA-negative RA...
  72. ncbi request reprint Satisfaction (not) guaranteed: re-evaluating the use of animal models of type 1 diabetes
    Bart O Roep
    Bart O Roep is at the Leiden University Medical Center, Department of Immunohematology and Blood Transfusion, Leiden NL 2300 RC, The Netherlands
    Nat Rev Immunol 4:989-97. 2004
    ....
  73. ncbi request reprint Genotype effects and epistasis in type 1 diabetes and HLA-DQ trans dimer associations with disease
    B P C Koeleman
    Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, The Netherlands
    Genes Immun 5:381-8. 2004
    ..This result provides new evidence for the potential importance of trans-encoded HLA DQ molecules in the determination of HLA-associated risk in T1D...
  74. ncbi request reprint Sequence variation within the major histocompatibility complex subregion centromeric of HLA class II in type 1 diabetes
    A R van der Slik
    Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Tissue Antigens 69:348-53. 2007
    ..We propose that studying genetic variants in the xMHC may be particularly rewarding to define disease pathways in patients displaying intermediate risk DQ-DR haplotypes...
  75. ncbi request reprint HLA class II associations with Type 1 diabetes mellitus: a multivariate approach
    R F Schipper
    Department of Immunohaematology and Bloodtransfusion, Leiden University Medical Center, Leiden, The Netherlands
    Tissue Antigens 57:144-50. 2001
    ..We confirm that the DR9DQ9/DR17DQ2 genotype is associated with susceptibility in the Dutch population, which has previously been noticed as a HLA risk genotypes in Asian populations only...
  76. ncbi request reprint HLA-DRB1*0403 is associated with dominant protection against IDDM in the general Dutch population and subjects with high-risk DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 genotype
    B O Roep
    Department of Immunohaematology and Blood Bank, Leiden University Medical Centre, The Netherlands
    Tissue Antigens 54:88-90. 1999
    ..We found that HLA-DRB1*0403 is strongly associated with dominant protection against development of IDDM in unrelated subject, even in the context of the highest risk HLA-DQ phenotypes and HLA-DR4-DQB1*0302 (P < 0.0001)...
  77. ncbi request reprint KIR in type 1 diabetes: disparate distribution of activating and inhibitory natural killer cell receptors in patients versus HLA-matched control subjects
    Arno R van der Slik
    Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Diabetes 52:2639-42. 2003
    ..035). We propose that the genetic imbalance between KIR and their HLA class 1 ligands may enhance the activation of T-cells with a low affinity for pancreatic self-antigens, thereby contributing to the pathogenesis of type 1 diabetes...
  78. doi request reprint Plasmid-encoded proinsulin preserves C-peptide while specifically reducing proinsulin-specific CD8⁺ T cells in type 1 diabetes
    Bart O Roep
    Department for Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands
    Sci Transl Med 5:191ra82. 2013
    ..Thus, we demonstrate that a plasmid encoding proinsulin reduces the frequency of CD8⁺ T cells reactive to proinsulin while preserving C-peptide over the course of dosing...
  79. pmc Association of interferon-gamma and interleukin 10 genotypes and serum levels with partial clinical remission in type 1 diabetes
    B Z Alizadeh
    Department of Immunohaematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands
    Clin Exp Immunol 145:480-4. 2006
    ..These data imply that remission is partially immune-mediated and involves regulation of IFN-gamma transcription...
  80. ncbi request reprint Insulin-like growth factor 1 promoter polymorphism influences insulin gene variable number of tandem repeat-associated risk for juvenile onset type 1 diabetes
    P Eerligh
    Department Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Tissue Antigens 63:568-71. 2004
    ..These results provide the first evidence for an association of IGF1 with T1D and imply that co-inheritance of these functional genetic variants of IGF1 and insulin predispose to T1D...
  81. ncbi request reprint Type 1 diabetes: how to resist a fatal attraction
    B O Roep
    Leiden University Medical Centre, Department of Immunohaematology and Blood Transfusion, The Netherlands
    Neth J Med 60:296-7. 2002
  82. ncbi request reprint Homing of human autoreactive T cells into pancreatic tissue of NOD-scid mice
    A G S van Halteren
    Department of Immunohematology and Blood Transfusion, E3Q, LUMC, PO Box 9600, 2300 RC, Leiden, The Netherlands
    Diabetologia 48:75-82. 2005
    ..We investigated the in vivo migration patterns of human islet-reactive T cell clones after transfer into compromised hosts...
  83. doi request reprint Immune modulation in humans: implications for type 1 diabetes mellitus
    Bart O Roep
    Leiden University Medical Center, Department of Immunohaematology and Blood Transfusion, P O Box 9600, NL 2300 RC Leiden, Netherlands
    Nat Rev Endocrinol 10:229-42. 2014
    ..In this Review, we discuss the current knowledge on immune regulation and dysfunction in humans that is the basis of tissue-specific immune regulation as an alternative to generalized immune suppression. ..
  84. ncbi request reprint Susceptibility loci for complex regional pain syndrome
    Willem Johan T van de Beek
    Department of Neurology, Leiden University Medical Center, P O Box 9600, 2300 RC, Leiden, The Netherlands
    Pain 103:93-7. 2003
    ..Additionally, an association with the D6S1014 locus was found, supporting the previous finding of an association with HLA-DR13...
  85. ncbi request reprint HLA-B8 in patients with the Lambert-Eaton myasthenic syndrome reduces likelihood of associated small cell lung carcinoma
    Paul W Wirtz
    Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
    Ann N Y Acad Sci 998:200-1. 2003
  86. ncbi request reprint IGF1 promoter polymorphism and cranial growth in individuals born very preterm
    Anne M Euser
    Department of Clinical Epidemiology, Leiden University Medical Center, The Netherlands
    Horm Res Paediatr 76:27-34. 2011
    ..Major defects in the IGF1 gene are associated with severely reduced cranial and linear growth. The association between IGF1 promoter polymorphisms and growth is uncertain...
  87. ncbi request reprint Enhanced concentrations of interleukin 16 are associated with joint destruction in patients with rheumatoid arthritis
    Leroy R Lard
    Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
    J Rheumatol 31:35-9. 2004
    ..To investigate the role of interleukin 16 (IL-16) in the development of rheumatoid arthritis (RA) and joint destruction...
  88. ncbi request reprint Autoimmunity in Addison's disease
    P Martín Martorell
    Leiden University Medical Centre, Department of Endocrinology, The Netherlands
    Neth J Med 60:269-75. 2002
    ..The adrenocortical function of patients positive for antibodies should be followed yearly...
  89. ncbi request reprint Modelling KIR-HLA genotype disparities in type 1 diabetes
    A R van der Slik
    Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Tissue Antigens 69:101-5. 2007
    ..However, logistic regression showed that activating KIR genotypes do influence the overall hierarchy of protection/susceptibility as reflected by composite inhibitory and activating KIR-HLA genotype models...
  90. ncbi request reprint A mini meta-analysis of studies on CD4+CD25+ T cells in human type 1 diabetes: report of the Immunology of Diabetes Society T Cell Workshop
    Timothy I M Tree
    Department of Immunobiology, King s College London, Guy s Hospital, London SE1 9RT, UK
    Ann N Y Acad Sci 1079:9-18. 2006
    ..We therefore performed a mini meta-analysis to compare the results in the four published studies, account for differences in their findings, and draw a consensus view on the role of this important cell subset in human T1DM...
  91. pmc Coxsackie B4 virus infection of beta cells and natural killer cell insulitis in recent-onset type 1 diabetic patients
    Francesco Dotta
    Department of Internal Medicine, Endocrine and Metabolic Sciences, and Biochemistry, University of Siena, 53100 Siena, Italy
    Proc Natl Acad Sci U S A 104:5115-20. 2007
    ..These studies provide direct evidence that enterovirus can infect beta cells in patients with type 1 diabetes and that infection is associated with inflammation and functional impairment...
  92. pmc DRB1*0401-restricted human T cell clone specific for the major proinsulin73-90 epitope expresses a down-regulatory T helper 2 phenotype
    Ivana Durinovic-Bello
    Department of Internal Medicine I, Division of Endocrinology, University of Ulm, D 89081 Ulm, Germany
    Proc Natl Acad Sci U S A 103:11683-8. 2006
    ....
  93. ncbi request reprint Enhancing the sensitivity of assays to detect T cell reactivity: the effect of cell separation and cryopreservation media
    Timothy I M Tree
    Department of Immunobiology, Guy s, King s and St Thomas School of Medicine, 2nd Floor, New Guy s House, Guy s Hospital London SE1 9RT, UK
    Ann N Y Acad Sci 1037:26-32. 2004
    ....
  94. ncbi request reprint Analysis of a functional BTNL2 polymorphism in type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus
    Gisela Orozco
    Instituto de Biomedicina, CSIC, Granada, Spain
    Hum Immunol 66:1235-41. 2005
    ..The BTNL2 rs2076530 polymorphism is associated with T1D, RA, and SLE because of its strong linkage disequalibrium with predisposing HLA DQB1-DRB1 haplotypes in Caucasian populations...
  95. ncbi request reprint Defective suppressor function in CD4(+)CD25(+) T-cells from patients with type 1 diabetes
    Shelley Lindley
    Department of Immunobiology, Guy s, King s and St Thomas School of Medicine, 2nd Floor, New Guy s House, Guy s Hospital London SE1 9RT, UK
    Diabetes 54:92-9. 2005
    ..007) and intracellular CTLA-4 (P = 0.01). These data demonstrate deficiency in function of the CD4(+)CD25(+) Treg population that may influence the pathogenesis of type 1 diabetes...
  96. ncbi request reprint Comparison of cytokine ELISpot assay formats for the detection of islet antigen autoreactive T cells. Report of the third immunology of diabetes society T-cell workshop
    Nanette C Schloot
    German Diabetes Research Institute at the Heinrich Heine University, Dusseldorf, Germany
    J Autoimmun 21:365-76. 2003
    ..The results demonstrate the potential for detection of low-level autoreactive T cell responses and identify assay characteristics that will be useful for studies in type 1 diabetes...
  97. ncbi request reprint Detection of autoreactive T cells in type 1 diabetes using coded autoantigens and an immunoglobulin-free cytokine ELISPOT assay: report from the fourth immunology of diabetes society T cell workshop
    Masao Nagata
    Department of Immunobiology, Guy s, King s and St Thomas School of Medicine, 2nd Floor, New Guy s House, Guy s Hospital, London SE1 9RT, UK
    Ann N Y Acad Sci 1037:10-5. 2004
    ..These results confirm the utility of the blinded performance of T cell assays as the most robust platform for assessing technologies to T cell autoreactivity...
  98. ncbi request reprint Processing and presentation of the islet autoantigen GAD by vascular endothelial cells promotes transmigration of autoreactive T-cells
    James E Greening
    Department of Immunology, Guy s, King s and St Thomas School of Medicine, Rayne Institute, 123 Coldharbour Lane, London SE5 9NU, U K
    Diabetes 52:717-25. 2003
    ..These results support the hypothesis that presentation of autoantigens by islet endothelium in vivo could promote transmigration of circulating islet autoantigen-specific T-cells primed in regional lymph nodes against islet autoantigens...
  99. ncbi request reprint HLA-DQ-regulated T-cell responses to islet cell autoantigens insulin and GAD65
    Timothy I M Tree
    Department of Immunology, Guy s, King s, and St Thomas School of Medicine, Denmark Hill Campus, Rayne Institute, London, UK
    Diabetes 53:1692-9. 2004
    ..These results indicate that HLA-DQ acts as a restriction element for both proliferative and suppressor cells, with the relative balance of these cells dependent on the nature of the autoantigen...
  100. pmc Autoreactive T cell responses show proinflammatory polarization in diabetes but a regulatory phenotype in health
    Sefina Arif
    Department of Immunobiology, Guy s, King s and St Thomas School of Medicine, King s College London, Guy s Campus, London, United Kingdom
    J Clin Invest 113:451-63. 2004
    ..We conclude that development of T1DM depends on the balance of autoreactive Th1 and Treg cells, which may be open to favorable manipulation by immune intervention...
  101. doi request reprint Islet antigen specific IL-10+ immune responses but not CD4+CD25+FoxP3+ cells at diagnosis predict glycemic control in type 1 diabetes
    Srinath Sanda
    Benaroya Research Institute and the University of Washington School of Medicine, 1201 9th Avenue, Seattle, WA 98101, USA
    Clin Immunol 127:138-43. 2008
    ..These data provide an immune phenotype of the honeymoon phase and suggest that analyzing IL-10 and FoxP3 at diagnosis may identify patients that will experience better glucose control...