| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From the Departments of Neurology (Drs. Smith–Jensen, Burgoon, Gilden, and Owens, and J. Anthony and H. Kraus) and Microbiology (Dr. Gilden), University of Colorado Health Sciences Center, Denver, CO.
Address correspondence and reprint requests to Dr. Donald H. Gilden, Department of Neurology, Mailstop B-182, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262.
OBJECTIVE: To better understand B-cell activation in MS by analyzing the immunoglobulin (Ig) G heavy chain variable region (VH) repertoire found in MS brains and comparing it with brain VH sequences in individuals with subacute sclerosing panencephalitis (SSPE)—a chronic encephalitis produced by measles virus (MV)—and characterized by an antigen-driven oligoclonal IgG response to MV antigens.
BACKGROUND: The specificity of oligoclonal IgG in MS CSF and plaques, and their relevance to the pathogenesis of MS is unknown.
METHODS: Nested PCR was used to amplify and sequence the rearranged IgG heavy-chain VH repertoire in plaques of three acute MS brains and in three SSPE brains. A representative population of VH sequences from each tissue was aligned to the known 51 functional VH germline segments. From this the authors determined the closest VH family germline segment, and the degree and location of somatic mutations for each unique IgG.
RESULTS: As expected for an antigen-driven response against MV antigens, most VH sequences from the SSPE brains were mutated extensively compared with their closest germline segments. Furthermore, SSPE VH sequences accumulated replacement mutations preferentially in the complementary-determining regions (CDRs) relative to framework regions—features normally observed during antigen-driven selection. A comparison of VH family and germline usage also demonstrated that each SSPE brain had its own unique IgG response. When the authors compared the VH response in MS plaques with SSPE, MS VH sequences were also mutated extensively, displayed a preferential accumulation of replacement mutations in CDRs, and were unique in each MS brain.
CONCLUSION: The presence of an antigen-driven response in MS, rather than a nonconventional mechanism of B-cell activation, warrants additional analysis of the specificity of IgG in MS brain and CSF.
Key words: Immunoglobulin G—MS brain.
This article has been cited by other articles:
|
|
 |
|
  S. L. Hauser, E. Waubant, D. L. Arnold, T. Vollmer, J. Antel, R. J. Fox, A. Bar-Or, M. Panzara, N. Sarkar, S. Agarwal, et al. B-Cell Depletion with Rituximab in Relapsing-Remitting Multiple Sclerosis N. Engl. J. Med., February 14, 2008; 358(7): 676 - 688. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. P. Owens, K. M. Winges, A. M. Ritchie, S. Edwards, M. P. Burgoon, L. Lehnhoff, K. Nielsen, J. Corboy, D. H. Gilden, and J. L. Bennett VH4 Gene Segments Dominate the Intrathecal Humoral Immune Response in Multiple Sclerosis J. Immunol., November 1, 2007; 179(9): 6343 - 6351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. P. Owens, A. M. Ritchie, D. H. Gilden, M. P. Burgoon, D. Becker, and J. L. Bennett Measles virus-specific plasma cells are prominent in subacute sclerosing panencephalitis CSF Neurology, May 22, 2007; 68(21): 1815 - 1819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. C. O'Connor, H. Appel, L. Bregoli, M. E. Call, I. Catz, J. A. Chan, N. H. Moore, K. G. Warren, S. J. Wong, D. A. Hafler, et al. Antibodies from Inflamed Central Nervous System Tissue Recognize Myelin Oligodendrocyte Glycoprotein J. Immunol., August 1, 2005; 175(3): 1974 - 1982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Burgoon, K. M. Keays, G. P. Owens, A. M. Ritchie, P. R. Rai, C. D. Cool, and D. H. Gilden Laser-capture microdissection of plasma cells from subacute sclerosing panencephalitis brain reveals intrathecal disease-relevant antibodies PNAS, May 17, 2005; 102(20): 7245 - 7250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Ritchie, D. H. Gilden, R. A. Williamson, M. P. Burgoon, X. Yu, K. Helm, J. R. Corboy, and G. P. Owens Comparative Analysis of the CD19+ and CD138+ Cell Antibody Repertoires in the Cerebrospinal Fluid of Patients with Multiple Sclerosis J. Immunol., July 1, 2004; 173(1): 649 - 656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. P. Owens, A. M. Ritchie, M. P. Burgoon, R. A. Williamson, J. R. Corboy, and D. H. Gilden Single-Cell Repertoire Analysis Demonstrates that Clonal Expansion Is a Prominent Feature of the B Cell Response in Multiple Sclerosis Cerebrospinal Fluid J. Immunol., September 1, 2003; 171(5): 2725 - 2733. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T Holmoy, B Vandvik, and F Vartdal T cells from multiple sclerosis patients recognize immunoglobulin G from cerebrospinal fluid Multiple Sclerosis, June 1, 2003; 9(3): 228 - 234. [Abstract] [PDF]
|
|
|
|
 |
|
 D. H. Gilden Viruses and Multiple Sclerosis JAMA, December 26, 2001; 286(24): 3127 - 3129. [Full Text] [PDF]
|
|
|
|
|
|
M. P. Burgoon, G. P. Owens, S. Carlson, A. L. Maybach, and D. H. Gilden Antigen Discovery in Chronic Human Inflammatory Central Nervous System Disease: Panning Phage-Displayed Antigen Libraries Identifies the Targets of Central Nervous System-Derived IgG in Subacute Sclerosing Panencephalitis J. Immunol., November 15, 2001; 167(10): 6009 - 6014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Derfuss, R. Gurkov, F. Then Bergh, N. Goebels, M. Hartmann, C. Barz, B. Wilske, I. Autenrieth, M. Wick, R. Hohlfeld, et al. Intrathecal antibody production against Chlamydia pneumoniae in multiple sclerosis is part of a polyspecific immune response Brain, July 1, 2001; 124(7): 1325 - 1335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. Gilden, M. P. Burgoon, B. K. Kleinschmidt-DeMasters, R. A. Williamson, O. Ghausi, D. R. Burton, and G. P. Owens Molecular Immunologic Strategies to Identify Antigens and B-Cell Responses Unique to Multiple Sclerosis Arch Neurol, January 1, 2001; 58(1): 43 - 48. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Cross MS: The return of the B cell Neurology, March 28, 2000; 54(6): 1214 - 1215. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
