Human anticardiolipin monoclonal autoantibodies cause placental necrosis and fetal loss in BALB/c mice

Wataru Ikematsu, Fu Lung Luan, Luigi La Rosa, Barbara Beltrami, Ferdinando Nicoletti, Jill P. Buyon, Pier Luigi Meroni, Genesio Balestrieri, Paolo Casali

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


Objective. To analyze the structure, specificity, and in vivo pathogenetic potential of 2 human anticardiolipin (aCL) monoclonal antibodies (MAb). Methods. Human aCL IgG MAb were generated from hybridized Epstein- Barr virus-induced B cell lines from a healthy subject (MAb 519) and from a patient with primary antiphospholipid syndrome (MAb 516). Studies of antigen- binding specificity and analysis of Ig V-gene mutations were carried out. The MAb were independently injected into mated female BALB/c mice, and their effect on pregnancy outcome was compared with that of MAb 57, a highly mutated and antigen-selected human IgG1λ rabies virus antibody. Results. Both MAb 519 and MAb 516 utilized minimally mutated V(H)D(H) and V(K)J(K) gene segments and bound cardiolipin and other anionic phospholipids in the absence of β2-glycoprotein I (β2-GPI). The mice injected with aCL MAb displayed a significantly higher rate of fetal resorption and a significant reduction in fetal and placental weight as compared with those injected with MAb 57. These findings were accompanied by a finding of placental human IgG deposition and necrosis in the aCL MAb-treated animals. Conclusion. The results of this study indicate that human aCL IgG that are β2-GPI independent can induce pathology.

Original languageEnglish (US)
Pages (from-to)1026-1039
Number of pages14
JournalArthritis and rheumatism
Issue number6
StatePublished - Jun 1998
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Immunology and Allergy
  • Rheumatology
  • Immunology


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