PMID- 9814697
OWN - NLM
STAT- MEDLINE
DCOM- 19990318
LR  - 20191102
IS  - 0961-2033 (Print)
IS  - 0961-2033 (Linking)
VI  - 7 Suppl 2
DP  - 1998
TI  - A chemically defined, toleragen-based approach for targeting 
      anti-beta2-glycoprotein I antibodies.
PG  - S166-9
AB  - Antiphospholipid syndrome is characterized by a prothrombotic state and the 
      presence of beta2-glycoprotein I (beta2-GPI)-dependent antiphospholipid 
      antibodies. The feasibility of a B cell tolerance-based approach for specific 
      reduction of anti-beta2-GPI antibodies was investigated. Anti-beta2-GPI 
      antibodies isolated from a patient with antiphospholipid syndrome were used to 
      screen peptide libraries expressed in phage, resulting in the identification of a 
      phage that specifically bound anti-beta2-GPI antibodies. The phage-displayed 
      peptide was identified and chemically optimized to generate a synthetic 14-mer 
      peptide with an internal thioether linkage (LJP 685) that retained the binding 
      profile of the original phage. LJP 685 was conjugated to a defined, 
      non-immunogenic organic platform to generate a tetravalent presentation of LJP 
      685 for use as a toleragen. Tetravalent LJP 685 induced a dose-dependent 
      reduction in antibody levels in mice previously immunized and boosted with LJP 
      685 coupled to the carrier keyhole limpet hemocyanin. These experiments support 
      the technical feasibility of a tolerance-based approach for reducing 
      anti-beta2-GPI antibodies in vivo.
FAU - Iverson, G M
AU  - Iverson GM
AD  - La Jolla Pharmaceutical Company, San Diego, CA 92121, USA.
FAU - Jones, D S
AU  - Jones DS
FAU - Marquis, D
AU  - Marquis D
FAU - Linnik, M D
AU  - Linnik MD
FAU - Victoria, E J
AU  - Victoria EJ
LA  - eng
PT  - Journal Article
PL  - England
TA  - Lupus
JT  - Lupus
JID - 9204265
RN  - 0 (Antibodies, Anticardiolipin)
RN  - 0 (Autoantigens)
RN  - 0 (Epitopes)
RN  - 0 (Glycoproteins)
RN  - 0 (LJP 685)
RN  - 0 (Oligonucleotides)
RN  - 0 (Peptide Fragments)
RN  - 0 (Peptides, Cyclic)
RN  - 0 (beta 2-Glycoprotein I)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibodies, Anticardiolipin/biosynthesis/*immunology/isolation & purification
MH  - Antibody Specificity
MH  - Antiphospholipid Syndrome/immunology/*therapy
MH  - Autoantigens/*immunology
MH  - Autoimmune Diseases/immunology/*therapy
MH  - B-Lymphocytes/*immunology
MH  - Bacteriophages/genetics
MH  - Chromatography, Affinity
MH  - Clonal Anergy
MH  - *Desensitization, Immunologic
MH  - Epitopes/*immunology/isolation & purification
MH  - Feasibility Studies
MH  - Female
MH  - Genetic Vectors/genetics
MH  - Glycoproteins/chemistry/*immunology
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Oligonucleotides/chemistry/immunology/*therapeutic use
MH  - Peptide Fragments/genetics/*immunology
MH  - Peptides, Cyclic/genetics/*immunology
MH  - beta 2-Glycoprotein I
EDAT- 1998/11/14 00:00
MHDA- 1998/11/14 00:01
CRDT- 1998/11/14 00:00
PHST- 1998/11/14 00:00 [pubmed]
PHST- 1998/11/14 00:01 [medline]
PHST- 1998/11/14 00:00 [entrez]
AID - 10.1177/096120339800700236 [doi]
PST - ppublish
SO  - Lupus. 1998;7 Suppl 2:S166-9. doi: 10.1177/096120339800700236.