VERNON HOLERS

Summary

Affiliation: University of Colorado Health Sciences Center
Country: USA

Publications

  1. ncbi Inhibition of the alternative complement activation pathway in traumatic brain injury by a monoclonal anti-factor B antibody: a randomized placebo-controlled study in mice
    Iris Leinhase
    Department of Trauma and Reconstructive Surgery, Charite University Medical School, Campus Benjamin Franklin, Berlin, Germany
    J Neuroinflammation 4:13. 2007
  2. ncbi Reduced neuronal cell death after experimental brain injury in mice lacking a functional alternative pathway of complement activation
    Iris Leinhase
    Department of Trauma and Reconstructive Surgery, Charite University Medical School, Campus Benjamin Franklin, 12200 Berlin, Germany
    BMC Neurosci 7:55. 2006
  3. ncbi The alternative pathway of complement in disease: opportunities for therapeutic targeting
    V Michael Holers
    Department of Medicine, University of Colorado Health Sciences Center, P O Box B 115, 4200 East Ninth Ave, Denver, CO 80262, USA
    Mol Immunol 41:147-52. 2004
  4. ncbi The complement system as a therapeutic target in autoimmunity
    V Michael Holers
    Department of Medicine and Immunology, Health Science Center, University of Colorado, Denver, CO 80262, USA
    Clin Immunol 107:140-51. 2003
  5. ncbi Are anti-cyclic citrullinated peptide antibodies pathogenic in rheumatoid arthritis?
    V Michael Holers
    Division of Rheumatology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    Nat Clin Pract Rheumatol 2:400-1. 2006
  6. ncbi Antibodies to citrullinated proteins: pathogenic and diagnostic significance
    V Michael Holers
    Division of Rheumatology, Department of Medicine, University of Colorado at Denver and Health Sciences Center, Mail Stop B115, P O Box 6511, Aurora, CO 80045, USA
    Curr Rheumatol Rep 9:396-400. 2007
  7. ncbi Complement receptors and the shaping of the natural antibody repertoire
    V Michael Holers
    Division of Rheumatology, Department of Medicine, B 115, University of Colorado Health Sciences Center, 4200 E 9th Avenue, Denver, CO 80262, USA
    Springer Semin Immunopathol 26:405-23. 2005
  8. ncbi Anti-C1q autoantibodies amplify pathogenic complement activation in systemic lupus erythematosus
    V Michael Holers
    Departments of Medicine and Immunology, University of Colorado Health Sciences Center, Denver, Colorado, USA
    J Clin Invest 114:616-9. 2004
  9. ncbi Phenotypes of complement knockouts
    V M Holers
    Division of Rheumatology, Box B 115, University of Colorado Health Sciences Center, Denver 80262, USA
    Immunopharmacology 49:125-31. 2000
  10. ncbi Complement receptor 2, natural antibodies and innate immunity: Inter-relationships in B cell selection and activation
    V Michael Holers
    Department of Immunology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    Mol Immunol 44:64-72. 2007

Research Grants

  1. Complement in the Pathogenesis of Autoimmune Arthritis
    VERNON HOLERS; Fiscal Year: 2009
  2. C3D/EBV RECEPTOR LIGAND BINDING SITES
    V Holers; Fiscal Year: 2006
  3. Evolution of Autoimmunity in Rheumatoid Arthritis
    V Holers; Fiscal Year: 2005
  4. Complement in the Pathogenesis of Autoimmune Arthritis
    VERNON HOLERS; Fiscal Year: 2007
  5. RA-Related Autoantibodies in Healthy FDR of RA Patients
    V Holers; Fiscal Year: 2007
  6. DENVER AUTOIMMUNITY CENTER OF EXCELLENCE
    V Holers; Fiscal Year: 2007
  7. RESEARCH TRAINING IN RHEUMATOLOGY
    V Holers; Fiscal Year: 2007
  8. MOUSE MEMBRANE RCA PROTEINS IN THE IMMUNE RESPONSE
    V Holers; Fiscal Year: 2007
  9. MOUSE MEMBRANE RCA PROTEINS IN THE IMMUNE RESPONSE
    V Holers; Fiscal Year: 2002
  10. C3D/EBV RECEPTOR LIGAND BINDING SITES
    V Holers; Fiscal Year: 2001

Detail Information

Publications83

  1. ncbi Inhibition of the alternative complement activation pathway in traumatic brain injury by a monoclonal anti-factor B antibody: a randomized placebo-controlled study in mice
    Iris Leinhase
    Department of Trauma and Reconstructive Surgery, Charite University Medical School, Campus Benjamin Franklin, Berlin, Germany
    J Neuroinflammation 4:13. 2007
    ..This neutralizing antibody represents a specific and potent inhibitor of the alternative complement pathway in mice...
  2. ncbi Reduced neuronal cell death after experimental brain injury in mice lacking a functional alternative pathway of complement activation
    Iris Leinhase
    Department of Trauma and Reconstructive Surgery, Charite University Medical School, Campus Benjamin Franklin, 12200 Berlin, Germany
    BMC Neurosci 7:55. 2006
    ....
  3. ncbi The alternative pathway of complement in disease: opportunities for therapeutic targeting
    V Michael Holers
    Department of Medicine, University of Colorado Health Sciences Center, P O Box B 115, 4200 East Ninth Ave, Denver, CO 80262, USA
    Mol Immunol 41:147-52. 2004
    ..It is also expected that several clinically relevant studies will be presented at the XXth International Complement Workshop that will identify additional areas of interest with regard to this pathway...
  4. ncbi The complement system as a therapeutic target in autoimmunity
    V Michael Holers
    Department of Medicine and Immunology, Health Science Center, University of Colorado, Denver, CO 80262, USA
    Clin Immunol 107:140-51. 2003
  5. ncbi Are anti-cyclic citrullinated peptide antibodies pathogenic in rheumatoid arthritis?
    V Michael Holers
    Division of Rheumatology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    Nat Clin Pract Rheumatol 2:400-1. 2006
  6. ncbi Antibodies to citrullinated proteins: pathogenic and diagnostic significance
    V Michael Holers
    Division of Rheumatology, Department of Medicine, University of Colorado at Denver and Health Sciences Center, Mail Stop B115, P O Box 6511, Aurora, CO 80045, USA
    Curr Rheumatol Rep 9:396-400. 2007
    ....
  7. ncbi Complement receptors and the shaping of the natural antibody repertoire
    V Michael Holers
    Division of Rheumatology, Department of Medicine, B 115, University of Colorado Health Sciences Center, 4200 E 9th Avenue, Denver, CO 80262, USA
    Springer Semin Immunopathol 26:405-23. 2005
    ..This review will examine the evidence that has accumulated over the last few years supporting these hypotheses...
  8. ncbi Anti-C1q autoantibodies amplify pathogenic complement activation in systemic lupus erythematosus
    V Michael Holers
    Departments of Medicine and Immunology, University of Colorado Health Sciences Center, Denver, Colorado, USA
    J Clin Invest 114:616-9. 2004
    ..These studies are the first, to our knowledge, to provide a causal link between anti-C1q antibodies and target organ damage in SLE...
  9. ncbi Phenotypes of complement knockouts
    V M Holers
    Division of Rheumatology, Box B 115, University of Colorado Health Sciences Center, Denver 80262, USA
    Immunopharmacology 49:125-31. 2000
    ..A discussion of future experimental directions thought to be important by this author then follows and concludes the review...
  10. ncbi Complement receptor 2, natural antibodies and innate immunity: Inter-relationships in B cell selection and activation
    V Michael Holers
    Department of Immunology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    Mol Immunol 44:64-72. 2007
    ....
  11. ncbi Complement receptor 2 and autoimmunity
    V Michael Holers
    Departments of Medicine and Immunology, University of Colorado Health Sciences Center, Denver, Colo, USA
    Curr Dir Autoimmun 7:33-48. 2004
    ....
  12. ncbi The spectrum of complement alternative pathway-mediated diseases
    V Michael Holers
    Department of Medicine and Immunology, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA
    Immunol Rev 223:300-16. 2008
    ..This article reviews evidence in support of the essential role of the alternative pathway in the generation of tissue injury and the rationale for development of therapies that modulate its activity...
  13. ncbi Cr2, a candidate gene in the murine Sle1c lupus susceptibility locus, encodes a dysfunctional protein
    S A Boackle
    Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    Immunity 15:775-85. 2001
    ..These data demonstrate a functionally significant phenotype for the NZM2410 Cr2 allele and strongly support its role as a lupus susceptibility gene...
  14. ncbi Inhibiting the complement system does not reduce injury in renal ischemia reperfusion
    P Park
    Department of Medicine, Section of Nephrology, The University of Chicago, 4841 S Maryland, Chicago, IL 60637, USA
    J Am Soc Nephrol 12:1383-90. 2001
    ..Thus, renal IRI in mice may have a partial complement dependence, yet pharmacologic inhibition of the complement system does not seem to be effective, likely because of the presence of other mediator systems that operate in parallel...
  15. ncbi Complement activation pathways in murine immune complex-induced arthritis and in C3a and C5a generation in vitro
    N K Banda
    Division of Rheumatology, University of Colorado Denver, Aurora, CO 80045, USA
    Clin Exp Immunol 159:100-8. 2010
    ..We conclude that neither the CP nor LP alone is capable of mediating CAIA in vivo and that mouse sera exhibits a high level of IgG-induced C5a generation in vitro through either the CP or AP...
  16. ncbi Epitope mapping using the X-ray crystallographic structure of complement receptor type 2 (CR2)/CD21: identification of a highly inhibitory monoclonal antibody that directly recognizes the CR2-C3d interface
    J M Guthridge
    Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    J Immunol 167:5758-66. 2001
    ..Thus, we have created an anti-human CR2 mAb that blocks the C3d ligand by direct contact with its interaction site, and we have provided confirmatory evidence that the C3d binding site seen in its crystal structure exists in solution...
  17. ncbi Modulation of renal disease in MRL/lpr mice genetically deficient in the alternative complement pathway factor B
    H Watanabe
    Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA
    J Immunol 164:786-94. 2000
    ....
  18. ncbi Complement component C3 is not required for full expression of immune complex glomerulonephritis in MRL/lpr mice
    H Sekine
    Department of Medicine, Medical University of South Carolina and the Medical Research Service, Ralph H Johnson Veterans Affairs Medical Center, Charleston, SC 29425, USA
    J Immunol 166:6444-51. 2001
    ..These results indicate that C3 and/or activation of C3 is not required for full expression of immune complex renal disease in MRL/lpr mice and may in fact play a beneficial role via clearance of immune complexes...
  19. ncbi A critical role for murine complement regulator crry in fetomaternal tolerance
    C Xu
    Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Science 287:498-501. 2000
    ..Thus, the regulation of complement is critical in fetal control of maternal processes that mediate tissue damage...
  20. ncbi Expression of a soluble complement inhibitor protects transgenic mice from antibody-induced acute renal failure
    B Schiller
    Department of Medicine, Section of Nephrology, The University of Chicago, Illinois 60637, USA
    J Am Soc Nephrol 12:71-9. 2001
    ..Animals that overexpress soluble Crry in renal tubules and elsewhere are protected from the acute renal failure that occurs in this model, which ultimately seems to develop because of complement activation focused on tubules...
  21. ncbi Structure of complement receptor 2 in complex with its C3d ligand
    G Szakonyi
    Department of Biochemistry and Molecular Genetics, University of Colorado Health Science Center, School of Medicine, Denver, CO 80262, USA
    Science 292:1725-8. 2001
    ..These results provide a detailed understanding of receptor-ligand interactions in this protein family and reveal potential target sites for molecular drug design...
  22. ncbi Expression of human complement receptor 2 (CR2, CD21) in Cr2-/- mice restores humoral immune function
    K J Marchbank
    Division of Rheumatology, Departments of Medicine and Immunology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    J Immunol 165:2354-61. 2000
    ..Therefore, hCR2-transgenic mice offer a valuable model system to further examine immunologic roles as well as structure-function relationships important for hCR2 function in primary cells in vivo...
  23. ncbi Structure of complement receptor (CR) 2 and CR2-C3d complexes
    J Hannan
    Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA
    Biochem Soc Trans 30:983-9. 2002
    ..To characterize this interaction further, several approaches directed at the determination of solution phase interactions as well as the analysis of the three-dimensional structure of CR2 alone and key CR2 mutants will be necessary...
  24. ncbi Characterization of C3-binding proteins on mouse neutrophils and platelets
    R J Quigg
    Department of Medicine, The University of Chicago, IL 60637, USA
    J Immunol 159:2438-44. 1997
    ..These appear to be distinct from the heretofore identified mouse B lymphocyte MCR1 and MCR2. The identity of these C3b- and C3d-binding proteins on mouse neutrophils and platelets awaits further study...
  25. ncbi CR2/CD21 proximal promoter activity is critically dependent on a cell type-specific repressor
    D Ulgiati
    Department of Immunology and Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    J Immunol 167:6912-9. 2001
    ..Thus, E2A activity is key not only for early B cell development, but also for controlling CR2 expression, a gene expressed only during later stages of ontogeny...
  26. ncbi Transgenic mice overexpressing the complement inhibitor crry as a soluble protein are protected from antibody-induced glomerular injury
    R J Quigg
    Department of Medicine, Section of Nephrology, The University of Chicago, Chicago, Illinois 60637, USA
    J Exp Med 188:1321-31. 1998
    ..These results support the hypothesis that continuous complement inhibition at the C3 convertase step is feasible and effective in complement-mediated injury states...
  27. ncbi A site in the complement receptor 2 (CR2/CD21) silencer is necessary for lineage specific transcriptional regulation
    K W Makar
    Department of Immunology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    Int Immunol 13:657-64. 2001
    ..These results demonstrate the importance of this site in regulating CR2 expression and suggest that CBF1, a component of the developmentally important Notch signaling pathway, may play a role in the control of human CR2 gene expression...
  28. ncbi Activation of complement mediates antiphospholipid antibody-induced pregnancy loss
    J E Salmon
    Department of Medicine, Hospital for Special Surgery Weill Medical College, Cornell University, New York, NY 10021, USA
    Lupus 12:535-8. 2003
    ....
  29. ncbi Cigarette smoking, disease severity and autoantibody expression in African Americans with recent-onset rheumatoid arthritis
    T R Mikuls
    Department of Medicine, University of Nebraska Medical Center and Omaha VA Medical Center, Omaha, NE 68198 6270, USA
    Ann Rheum Dis 67:1529-34. 2008
    ....
  30. ncbi Complement activation as a mediator of antiphospholipid antibody induced pregnancy loss and thrombosis
    J E Salmon
    Department of Medicine, Hospital for Special Surgery-Weill Medical College, Cornell University, New York 10021, USA
    Ann Rheum Dis 61:ii46-50. 2002
  31. ncbi Structural studies in solution of the recombinant N-terminal pair of short consensus/complement repeat domains of complement receptor type 2 (CR2/CD21) and interactions with its ligand C3dg
    J M Guthridge
    Department of Medicine, Division of Rheumatology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
    Biochemistry 40:5931-41. 2001
    ..Sedimentation modeling showed that the arrangement of the two SCR domains in CR2 SCR 1-2 is highly extended in solution...
  32. ncbi Intrinsic B cell hypo-responsiveness in mice prematurely expressing human CR2/CD21 during B cell development
    Liudmila Kulik
    Department of Medicine and Immunology, UCHSC, Denver, CO 80262, USA
    Eur J Immunol 37:623-33. 2007
    ..Overall, these data suggest that premature hCR2 expression and the consequences thereof during B cell development intrinsically alters the way mature B cells develop and subsequently respond to antigen through the BCR signaling complex...
  33. ncbi Antibodies against citrullinated proteins enhance tissue injury in experimental autoimmune arthritis
    Kristine A Kuhn
    Department of Immunology and Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA
    J Clin Invest 116:961-73. 2006
    ..These results demonstrate that antibodies against citrullinated proteins are centrally involved in the pathogenesis of autoimmune arthritis...
  34. ncbi Defective B cell ontogeny and immune response in human complement receptor 2 (CR2, CD21) transgenic mice is partially recovered in the absence of C3
    Jason Twohig
    Department of Medical Biochemistry and Immunology, Cardiff University, Heath Park, Cardiff CF14 4XX, UK
    Mol Immunol 44:3434-44. 2007
    ....
  35. ncbi Alternative complement pathway activation is essential for inflammation and joint destruction in the passive transfer model of collagen-induced arthritis
    Nirmal K Banda
    Divisions of Rheumatology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    J Immunol 177:1904-12. 2006
    ..The mechanisms by which these target organ-specific mAbs bypass the requirements for engagement of the classical pathway remain to be defined but do not appear to involve a lack of alternative pathway regulatory proteins...
  36. ncbi Factor B of the alternative complement pathway regulates development of airway hyperresponsiveness and inflammation
    Christian Taube
    Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA
    Proc Natl Acad Sci U S A 103:8084-9. 2006
    ..These results demonstrate that in sensitized hosts complement activation through the alternative pathway after allergen exposure is critical to the development of AHR and airway inflammation...
  37. ncbi Pharmacological complement inhibition at the C3 convertase level promotes neuronal survival, neuroprotective intracerebral gene expression, and neurological outcome after traumatic brain injury
    Iris Leinhase
    Department of Trauma and Reconstructive Surgery, Charite University Medical School, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany
    Exp Neurol 199:454-64. 2006
    ..These data suggest that pharmacological complement inhibition represents a promising approach for attenuation of neuroinflammation and secondary neurodegeneration after head injury...
  38. ncbi Characterization of human complement receptor type 2 (CR2/CD21) as a receptor for IFN-alpha: a potential role in systemic lupus erythematosus
    Rengasamy Asokan
    Department of Medicine and Department of Immunology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA
    J Immunol 177:383-94. 2006
    ....
  39. ncbi The alternative pathway of complement activation is critical for blister induction in experimental epidermolysis bullosa acquisita
    Sidonia Mihai
    Department of Dermatology, University of Lubeck, Lubeck, Germany, and Department of Pediatrics, Laboratory of Developmental Immunology, Massachusetts General Hospital, Boston 02115, USA
    J Immunol 178:6514-21. 2007
    ....
  40. ncbi Complement activation fragment Bb in early pregnancy and spontaneous preterm birth
    Anne M Lynch
    Department of Obstetrics and Gynecology, University of Colorado Denver, Denver, CO 80045, USA
    Am J Obstet Gynecol 199:354.e1-8. 2008
    ....
  41. ncbi Evidence for non-traditional activation of complement factor C3 during murine liver regeneration
    Amelia Clark
    Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, United States
    Mol Immunol 45:3125-32. 2008
    ..In vitro analysis raises the possibility that plasmin may contribute to non-traditional complement activation during liver regeneration in vivo...
  42. ncbi Complement receptor CR2/CR1 deficiency protects mice from collagen-induced arthritis and associates with reduced autoantibodies to type II collagen and citrullinated antigens
    Kristine A Kuhn
    Departments of Immunology and Medicine, University of Colorado Health Sciences Center, Aurora, CO 80045, USA
    Mol Immunol 45:2808-19. 2008
    ....
  43. ncbi The HLA-DRB1 shared epitope is associated with susceptibility to rheumatoid arthritis in African Americans through European genetic admixture
    Laura B Hughes
    University of Alabama at Birmingham 35294 2182, USA
    Arthritis Rheum 58:349-58. 2008
    ....
  44. ncbi Alternative complement pathway activation fragment Bb in early pregnancy as a predictor of preeclampsia
    Anne M Lynch
    Department of Obstetrics and Gynecology, University of Colorado at Denver and Health Sciences Center, Denver, CO, USA
    Am J Obstet Gynecol 198:385.e1-9. 2008
    ..The purpose of this study was to determine whether elevated levels of the activation fragment Bb in early pregnancy are predictive of preeclampsia...
  45. ncbi A complement C3 inhibitor specifically targeted to sites of complement activation effectively ameliorates collagen-induced arthritis in DBA/1J mice
    Hongbin Song
    Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA
    J Immunol 179:7860-7. 2007
    ..Of interest, a previous study reported that Crry-Ig, an untargeted counterpart of CR2-Crry, had minimal effect on disease, even when administered at a sufficiently high dose to maintain chronic complement inhibition...
  46. ncbi Isolating the Epstein-Barr virus gp350/220 binding site on complement receptor type 2 (CR2/CD21)
    Kendra A Young
    Department of Medicine and Immunology, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado 80045, USA
    J Biol Chem 282:36614-25. 2007
    ....
  47. ncbi Pathogenic complement activation in collagen antibody-induced arthritis in mice requires amplification by the alternative pathway
    Nirmal K Banda
    Division of Rheumatology B115, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045, USA
    J Immunol 179:4101-9. 2007
    ..These results indicate that the alternative pathway amplification loop, with its ability to greatly enhance C3 activation, is necessary to mediate inflammatory arthritis induced by adherent immune complexes...
  48. ncbi Cutting edge: Complement (C3d)-linked antigens break B cell anergy
    Taras Lyubchenko
    Division of Rheumatology, Department of Medicine, University of Colorado School of Medicine, Denver, CO 802602, USA
    J Immunol 179:2695-9. 2007
    ..This mechanism may place individuals exposed to complement-fixing bacteria at risk for autoimmunity...
  49. ncbi The alternative pathway of complement is activated in the glomeruli and tubulointerstitium of mice with adriamycin nephropathy
    Amanda M Lenderink
    Department of Medicine, University of Colorado, Denver, USA
    Am J Physiol Renal Physiol 293:F555-64. 2007
    ..These results demonstrate that complement activation in this nonimmune complex-mediated model of progressive renal disease requires an intact alternative pathway...
  50. ncbi Role for CD21 in the establishment of an extracellular HIV reservoir in lymphoid tissues
    Jason Ho
    Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 178:6968-74. 2007
    ..Our findings demonstrate a critical role for CD21 in HIV trapping by LN cells and suggest a new therapeutic avenue for reducing HIV reservoirs...
  51. ncbi C3a is required for the production of CXC chemokines by tubular epithelial cells after renal ishemia/reperfusion
    Joshua M Thurman
    Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    J Immunol 178:1819-28. 2007
    ..This innate immune system thereby recognizes hypoxic injury and triggers a systemic inflammatory response through the generation of C3a and subsequent activation of the NF-kappaB system...
  52. ncbi Treatment with an inhibitory monoclonal antibody to mouse factor B protects mice from induction of apoptosis and renal ischemia/reperfusion injury
    Joshua M Thurman
    Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA, and Department of Pathology, University Hospital Dubrava, Zabreb, Croatia
    J Am Soc Nephrol 17:707-15. 2006
    ..Thus, use of an inhibitory mAb to mouse factor B effectively prevented activation of complement in the kidney after I/R and protected the mice from necrotic and apoptotic injury of the tubules...
  53. ncbi Altered renal tubular expression of the complement inhibitor Crry permits complement activation after ischemia/reperfusion
    Joshua M Thurman
    Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
    J Clin Invest 116:357-68. 2006
    ..Increased C3 mRNA and decreased factor H mRNA were also detected in the outer medulla after I/R, suggesting that altered synthesis of these factors might further contribute to complement activation in this location...
  54. ncbi Administration of the soluble complement inhibitor, Crry-Ig, reduces inflammation and aquaporin 4 expression in lupus cerebritis
    Jessy J Alexander
    Department of Medicine, Section of Nephrology, University of Chicago, Chicago, IL 60637, USA
    Biochim Biophys Acta 1639:169-76. 2003
    ..It is conceivable that increased AQ4 expression results in cerebral edema and hence complement inhibition may provide a new therapeutic option in inflammatory cerebral disorders such as lupus cerebritis...
  55. ncbi Can we accurately predict the development of rheumatoid arthritis in the preclinical phase?
    Darcy S Majka
    Arthritis Rheum 48:2701-5. 2003
  56. ncbi Inhibition of complement activation decreases airway inflammation and hyperresponsiveness
    Christian Taube
    Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA
    Am J Respir Crit Care Med 168:1333-41. 2003
    ..These results suggest that prevention of complement activation may have a therapeutic role in the treatment of allergic airway inflammation and asthma in sensitized individuals...
  57. ncbi Prevention of collagen-induced arthritis in mice transgenic for the complement inhibitor complement receptor 1-related gene/protein y
    Nirmal K Banda
    Division of Rheumatology, University of Colorado Health Sciences Center, Denver, CO 80262 BolderPATH, Boulder, CO 80309, USA
    J Immunol 171:2109-15. 2003
    ..These results suggest that suppression of CIA in Crry-Tg mice may be due to enhanced synthesis of Crry locally in the joint with decreased production of proinflammatory cytokines...
  58. ncbi Complement receptor 2-mediated targeting of complement inhibitors to sites of complement activation
    Hongbin Song
    Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    J Clin Invest 111:1875-85. 2003
    ..Finally, the in vivo validity of the targeting strategy was confirmed by the demonstration that CR2-DAF, but not soluble DAF, targets to the kidney in mouse models of lupus nephritis that are associated with renal complement deposition...
  59. ncbi The extended multidomain solution structures of the complement protein Crry and its chimeric conjugate Crry-Ig by scattering, analytical ultracentrifugation and constrained modelling: implications for function and therapy
    Mohammed Aslam
    Department of Biochemistry and Molecular Biology, Darwin Building, University College London, Gower Street, London WC1E 6BT, UK
    J Mol Biol 329:525-50. 2003
    ..A structural comparison between Crry and complement receptor type 1 indicated that the domain arrangement of Crry SCR 1-3 is as extended as that of the CR1 SCR 15-17 NMR structure...
  60. ncbi Administration of a soluble recombinant complement C3 inhibitor protects against renal disease in MRL/lpr mice
    Lihua Bao
    Section of Nephrology, The University of Chicago, Illinois 60637, USA
    J Am Soc Nephrol 14:670-9. 2003
    ..Thus, inhibition of complement activation with Crry-Ig significantly reduces renal disease in MRL/lpr lupus mice. The data support the strategy of using recombinant complement C3 inhibitors to treat human lupus nephritis...
  61. ncbi Lack of a functional alternative complement pathway ameliorates ischemic acute renal failure in mice
    Joshua M Thurman
    Division of Nephrology University of Colorado Health Sciences Center, Denver, CO 80262, USA
    J Immunol 170:1517-23. 2003
    ..Our results demonstrate that complement activation in the kidney after I/R occurs exclusively via the alternative pathway, and that selective inhibition of this pathway provides protection to the kidneys from ischemic ARF...
  62. ncbi Role of complement in the development of autoimmunity
    Susan A Boackle
    University of Colorado Health Sciences Center, Denver, Colo, USA
    Curr Dir Autoimmun 6:154-68. 2003
    ..Understanding the mechanisms by which these receptors participate in the maintenance of B cell tolerance will be critical in developing appropriate therapeutic interventions for patients with autoimmune diseases such as SLE...
  63. ncbi Expression of human complement receptor type 2 (CD21) in mice during early B cell development results in a reduction in mature B cells and hypogammaglobulinemia
    Kevin J Marchbank
    Complement Biology Group, Department of Medical Biochemistry, University of Wales College of Medicine, Heath Park, Cardiff, United Kingdom
    J Immunol 169:3526-35. 2002
    ..Alterations in B cell development are most likely due to engagement of pre-B cell receptor-mediated or other regulatory pathways by hCR2 in a CD19- and possibly C3 ligand-dependent manner...
  64. ncbi Mice deficient in complement receptors 1 and 2 lack a tissue injury-inducing subset of the natural antibody repertoire
    Sherry D Fleming
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
    J Immunol 169:2126-33. 2002
    ..In sum, CR2/CR1 play an unanticipated but critical role in the development of a subset of the natural Ab repertoire that has particular importance in the pathogenesis of IR injury...
  65. ncbi Transgenic expression of a soluble complement inhibitor protects against renal disease and promotes survival in MRL/lpr mice
    Lihua Bao
    Department of Medicine, Section of Nephrology, University of Chicago, Chicago, IL 60637, USA
    J Immunol 168:3601-7. 2002
    ..Thus, long-term complement inhibition reduces renal disease in MRL/lpr mice, which translates into improved survival. MRL/lpr mice in which complement is inhibited still have spontaneous mortality, yet this is not from renal disease...
  66. ncbi Arthritis critically dependent on innate immune system players
    Hong Ji
    Section on Immunology and Immunogenetics, Joslin Diabetes Center, Boston, MA 02215, USA
    Immunity 16:157-68. 2002
    ..We suggest that autoimmune disease, even one that is organ specific, can occur when mobilization of an adaptive immune response results in runaway activation of the innate response...
  67. ncbi Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome
    Guillermina Girardi
    Department of Medicine, Hospital for Special Surgery Weill Medical College, Cornell University, 535 East 70th Street, New York, New York 10021, USA
    J Clin Invest 112:1644-54. 2003
    ..Our findings identify the key innate immune effectors engaged by pathogenic autoantibodies that mediate poor pregnancy outcomes in APS and provide novel and important targets for prevention of pregnancy loss in APS...
  68. ncbi Effects of complement factor D deficiency on the renal disease of MRL/lpr mice
    Margaret K Elliott
    Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
    Kidney Int 65:129-38. 2004
    ....
  69. ncbi Targeted complement inhibition by C3d recognition ameliorates tissue injury without apparent increase in susceptibility to infection
    Carl Atkinson
    Department of Microbiology and Immunology, Children s Research Institute, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    J Clin Invest 115:2444-53. 2005
    ..Thus, compared with systemic inhibition, CR2-mediated targeting of a complement inhibitor of activation improved bioavailability, significantly enhanced efficacy, and maintained host resistance to infection...
  70. ncbi B cells from mice prematurely expressing human complement receptor type 2 are unresponsive to T-dependent antigens
    Louise Birrell
    Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, UK
    J Immunol 174:6974-82. 2005
    ..We conclude that this phenotype and these mice may offer an additional means to dissect mechanisms underlying B cell tolerance and Ag responsiveness both in bone marrow and periphery...
  71. ncbi Coligation of the B cell receptor with complement receptor type 2 (CR2/CD21) using its natural ligand C3dg: activation without engagement of an inhibitory signaling pathway
    Taras Lyubchenko
    Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80220, USA
    J Immunol 174:3264-72. 2005
    ....
  72. ncbi Innate autoimmunity
    Michael C Carroll
    CBR Institute for Biomedical Research, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    Adv Immunol 86:137-57. 2005
    ....
  73. ncbi Acute tubular necrosis is characterized by activation of the alternative pathway of complement
    Joshua M Thurman
    Department of Internal Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
    Kidney Int 67:524-30. 2005
    ..The purpose of this study was to determine whether alternative pathway activation also occurs during the development of ischemic acute tubular necrosis in the human kidney...
  74. ncbi Antibodies against cyclic citrullinated peptide are associated with HLA-DR4 in simplex and multiplex polyarticular-onset juvenile rheumatoid arthritis
    Elizabeth D Ferucci
    Division of Rheumatology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA
    Arthritis Rheum 52:239-46. 2005
    ..Anti-CCP antibodies in JRA are associated with polyarticular onset, a polyarticular course, and erosive disease...
  75. ncbi Anti-phospholipid antibodies restore mesenteric ischemia/reperfusion-induced injury in complement receptor 2/complement receptor 1-deficient mice
    Sherry D Fleming
    Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
    J Immunol 173:7055-61. 2004
    ..We conclude that anti-phospholipid Abs can bind to tissues subjected to I/R insult and mediate tissue damage...
  76. ncbi A novel inhibitor of the alternative complement pathway prevents antiphospholipid antibody-induced pregnancy loss in mice
    Joshua M Thurman
    Division of Nephrology and Hypertension, University of Colorado Health Sciences Center, 4200 E 9th Avenue, B 115, Denver, CO 80262, USA
    Mol Immunol 42:87-97. 2005
    ..The mAb protects mice in an in vivo model of antiphospholipid antibody syndrome, demonstrating the therapeutic potential for the inhibition of factor B in this disease...
  77. ncbi CR1/CR2 deficiency alters IgG3 autoantibody production and IgA glomerular deposition in the MRL/lpr model of SLE
    Susan A Boackle
    Department of Medicine and Immunology, Division of Rheumatology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    Autoimmunity 37:111-23. 2004
    ..Together these data support the concept that alterations in CR1/CR2 expression or function affect the regulation of autoantibody production and/or clearance and may have clinical consequences...
  78. ncbi Complement activation is critical to airway hyperresponsiveness after acute ozone exposure
    Jung-Won Park
    Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA
    Am J Respir Crit Care Med 169:726-32. 2004
    ..However, this neutrophil response does not appear necessary for the development of AHR...
  79. ncbi Complement C3 activation is required for antiphospholipid antibody-induced fetal loss
    V Michael Holers
    Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    J Exp Med 195:211-20. 2002
    ..While antigenic epitopes recognized by aPL antibodies are important in the pathogenesis of APS, our data show that in vivo complement activation is required for aPL antibody-induced fetal loss and growth retardation...
  80. ncbi Structure of the Epstein-Barr virus major envelope glycoprotein
    Gerda Szakonyi
    Department of Molecular and Computational Biology, University of Southern California, 1050 Childs Way, Los Angeles, California 90089, USA
    Nat Struct Mol Biol 13:996-1001. 2006
    ..These results provide structural information for developing drugs and vaccines to prevent infection by EBV and related viruses...
  81. ncbi Candidate inhibitors of porcine complement
    Ebbe B Thorgersen
    Institute of Immunology, Rikshospitalet Radiumhospitalet Medical Center and University of Oslo, N 0027 Oslo, Norway
    Mol Immunol 44:1827-34. 2007
    ..05 mg/mL for all three activators. All candidates tested inhibited porcine complement activation, but in different ways and to different degrees. Of the complement-specific candidates, VCP inhibited all activators completely at low doses...
  82. ncbi Molecular basis of the interaction between complement receptor type 2 (CR2/CD21) and Epstein-Barr virus glycoprotein gp350
    Kendra A Young
    Institute of Structural Biology and Molecular Biology, School of Biological Sciences, Mayfield Road, University of Edinburgh, Edinburgh EH9 3JR, Scotland, United Kingdom
    J Virol 82:11217-27. 2008
    ..The mutagenesis data were used to calculate a model of the CR2-gp350 complex using the soft-docking program HADDOCK...
  83. ncbi Extended flexible linker structures in the complement chimaeric conjugate CR2-Ig by scattering, analytical ultracentrifugation and constrained modelling: implications for function and therapy
    Hannah E Gilbert
    Department of Biochemistry and Molecular Biology, Darwin Building, University College London, UK
    J Mol Biol 356:397-412. 2006
    ..The modelling also confirmed that the structure of CR2 SCR 1-2 is more extended in solution than in its crystal structure...

Research Grants41

  1. Complement in the Pathogenesis of Autoimmune Arthritis
    VERNON HOLERS; Fiscal Year: 2009
    ....
  2. C3D/EBV RECEPTOR LIGAND BINDING SITES
    V Holers; Fiscal Year: 2006
    ....
  3. Evolution of Autoimmunity in Rheumatoid Arthritis
    V Holers; Fiscal Year: 2005
    ..abstract_text> ..
  4. Complement in the Pathogenesis of Autoimmune Arthritis
    VERNON HOLERS; Fiscal Year: 2007
    ....
  5. RA-Related Autoantibodies in Healthy FDR of RA Patients
    V Holers; Fiscal Year: 2007
    ....
  6. DENVER AUTOIMMUNITY CENTER OF EXCELLENCE
    V Holers; Fiscal Year: 2007
    ..This latter project involves a newly established collaboration with a separate institution and group of clinicians skilled in the clinical investigation of RA. ..
  7. RESEARCH TRAINING IN RHEUMATOLOGY
    V Holers; Fiscal Year: 2007
    ..D. scientists who will hold successful academic research positions. ..
  8. MOUSE MEMBRANE RCA PROTEINS IN THE IMMUNE RESPONSE
    V Holers; Fiscal Year: 2007
    ..Specific Aim #3: Determine the functional activities and biologic relevance of novel SCR-containing candidate C3/C4 binding and regulatory proteins. ..
  9. MOUSE MEMBRANE RCA PROTEINS IN THE IMMUNE RESPONSE
    V Holers; Fiscal Year: 2002
    ....
  10. C3D/EBV RECEPTOR LIGAND BINDING SITES
    V Holers; Fiscal Year: 2001
    ..3) to establish the 3-dimensional solution phase structure of a longer CR2 region containing the SCR 1-2 domain and determine whether the orientation of this domain is influenced by its carboxy-terminal flanking SCRs. ..
  11. ANALYSIS OF C3D/EBV RECEPTOR (CR2) LIGAND BINDING SITES
    V Holers; Fiscal Year: 1993
    ..This understanding will allow further experimental and perhaps better clinical approaches to immunotherapy and anti-viral therapy mediated through CR2...
  12. MOUSE MEMBRANE RCA PROTEINS IN THE IMMUNE RESPONSE
    V Holers; Fiscal Year: 1993
    ....