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Pathogenic antiphospholipid antibody: an antigen-selected needle in a haystack.
- Source :
-
Blood [Blood] 2004 Sep 15; Vol. 104 (6), pp. 1711-5. Date of Electronic Publication: 2004 May 27. - Publication Year :
- 2004
-
Abstract
- Antiphospholipid antibodies represent a heterogeneous group of autoantibodies directed against anionic phospholipids (PLs) usually linked to protein cofactors. Their presence during the antiphospholipid syndrome is associated with risks of thrombosis and fetal losses. Among 5 randomly selected monoclonal antiphospholipid antibodies, all originating from a single patient suffering from this autoimmune disease, only 1 induced fetal losses when passively injected into pregnant mice. Its antiphospholipid activity was dependent on annexin A5, and its variable regions contained mainly 3 replacement mutations. To clarify the role of these mutations in the pathogenicity of the antibody, they were in vitro reverted to the germ line configuration. The resulting "germ line" antibody reacted with multiple self-antigens and only partially lost its reactivity against PLs, but it was no more dependent on annexin A5 and, more importantly, was no more pathogenic. This study illustrates that the in vivo antigen-driven maturation process of natural autoreactive B cells can be responsible for pathogenicity.
- Subjects :
- Adult
Animals
Annexins metabolism
Antibodies, Antiphospholipid chemistry
Antibodies, Antiphospholipid genetics
Antibodies, Monoclonal chemistry
Antibodies, Monoclonal genetics
Antibodies, Monoclonal immunology
Antibodies, Monoclonal toxicity
Autoantibodies chemistry
Autoantibodies genetics
Base Sequence
Enzyme-Linked Immunosorbent Assay
Female
Fetal Death chemically induced
Fetal Death immunology
Germ-Line Mutation genetics
Humans
Mice
Models, Molecular
Molecular Sequence Data
Pregnancy
Protein Structure, Tertiary
Antibodies, Antiphospholipid immunology
Antibodies, Antiphospholipid toxicity
Antigens immunology
Antiphospholipid Syndrome immunology
Autoantibodies immunology
Autoantibodies toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 104
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 15166038
- Full Text :
- https://doi.org/10.1182/blood-2004-02-0462