PMID- 10746589
OWN - NLM
STAT- MEDLINE
DCOM- 20000818
LR  - 20190514
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 54
IP  - 6
DP  - 2000 Mar 28
TI  - Comparison of immunoglobulin G heavy-chain sequences in MS and SSPE brains 
      reveals an antigen-driven response.
PG  - 1227-32
AB  - 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.
FAU - Smith-Jensen, T
AU  - Smith-Jensen T
AD  - Department of Neurology, University of Colorado Health Sciences Center, Denver 
      80262, USA.
FAU - Burgoon, M P
AU  - Burgoon MP
FAU - Anthony, J
AU  - Anthony J
FAU - Kraus, H
AU  - Kraus H
FAU - Gilden, D H
AU  - Gilden DH
FAU - Owens, G P
AU  - Owens GP
LA  - eng
GR  - AG 06127/AG/NIA NIH HHS/United States
GR  - NS 07321/NS/NINDS NIH HHS/United States
GR  - NS 32623/NS/NINDS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (Immunoglobulin G)
RN  - 0 (RNA Probes)
SB  - IM
CIN - Neurology. 2000 Mar 28;54(6):1214-5. PMID: 10746584
MH  - Adolescent
MH  - Adult
MH  - Blotting, Northern
MH  - Brain/*immunology/*pathology
MH  - Female
MH  - Gene Library
MH  - Humans
MH  - Immunoglobulin G/*genetics/*immunology
MH  - Male
MH  - Multiple Sclerosis/*genetics/immunology/pathology
MH  - RNA Probes
MH  - Subacute Sclerosing Panencephalitis/*genetics/immunology/pathology
EDAT- 2000/04/04 09:00
MHDA- 2000/08/29 11:01
CRDT- 2000/04/04 09:00
PHST- 2000/04/04 09:00 [pubmed]
PHST- 2000/08/29 11:01 [medline]
PHST- 2000/04/04 09:00 [entrez]
AID - 10.1212/wnl.54.6.1227 [doi]
PST - ppublish
SO  - Neurology. 2000 Mar 28;54(6):1227-32. doi: 10.1212/wnl.54.6.1227.