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Significance of valine/leucine247 polymorphism of beta2-glycoprotein I in antiphospholipid syndrome: increased reactivity of anti-beta2-glycoprotein I autoantibodies to the valine247 beta2-glycoprotein I variant
- Source :
- Arthritis and rheumatism. 52(1)
- Publication Year :
- 2005
-
Abstract
- To clarify the consequences of the valine/leucine polymorphism at position 247 of the beta(2)-glycoprotein I (beta(2)GPI) gene in patients with antiphospholipid syndrome (APS), by investigating the correlation between genotypes and the presence of anti-beta(2)GPI antibody. The reactivity of anti-beta(2)GPI antibodies was characterized using recombinant Val(247) and Leu(247) beta(2)GPI.Sixty-five Japanese patients with APS and/or systemic lupus erythematosus who were positive for antiphospholipid antibodies and 61 controls were analyzed for the presence of the Val/Leu(247) polymorphism of beta(2)GPI. Polymorphism assignment was determined by polymerase chain reaction followed by restriction enzyme digestion. Recombinant Val(247) and Leu(247) beta(2)GPI were established to compare the reactivity of anti-beta(2)GPI antibodies to beta(2)GPI between these variants. The variants were prepared on polyoxygenated plates or cardiolipin-coated plates, and the reactivity of a series of anti-beta(2)GPI antibodies (immunized anti-human beta(2)GPI monoclonal antibodies [Cof-19-21] and autoimmune anti-beta(2)GPI monoclonal antibodies [EY1C8, EY2C9, and TM1G2]) and IgGs purified from patient sera was investigated.A positive correlation between the Val(247) allele and the presence of anti-beta(2)GPI antibodies was observed in the patient group. Human monoclonal/polyclonal anti-beta(2)GPI autoantibodies showed higher binding to recombinant Val(247) beta(2)GPI than to Leu(247) beta(2)GPI, although no difference in the reactivity of the immunized anti-beta(2)GPI between these variants was observed. Conformational optimization showed that the replacement of Leu(247) by Val(247) led to a significant alteration in the tertiary structure of domain V and/or the domain IV-V interaction.The Val(247) beta(2)GPI allele was associated with both a high frequency of anti-beta(2)GPI antibodies and stronger reactivity with anti-beta(2)GPI antibodies compared with the Leu(247) beta(2)GPI allele, suggesting that the Val(247) beta(2)GPI allele may be one of the genetic risk factors for development of APS.
- Subjects :
- Adult
Male
medicine.drug_class
Immunology
Molecular Conformation
Monoclonal antibody
law.invention
Rheumatology
Antiphospholipid syndrome
law
Leucine
Genotype
medicine
Immunology and Allergy
Humans
Pharmacology (medical)
Aged
Autoantibodies
Glycoproteins
Polymorphism, Genetic
biology
Autoantibody
Valine
Middle Aged
medicine.disease
Antiphospholipid Syndrome
Polyclonal antibodies
beta 2-Glycoprotein I
Antibodies, Anticardiolipin
Monoclonal
biology.protein
Recombinant DNA
Female
Antibody
Subjects
Details
- ISSN :
- 00043591
- Volume :
- 52
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Arthritis and rheumatism
- Accession number :
- edsair.doi.dedup.....0518ac1e3cc455cd41aaffdf58bd862c