Molecular definition of human β2-glycoprotein (α2-GPI) by cDNA cloning and inter-species differences of β2-GPI in alternation of anticardiolipin binding

Matsuura Eiji, Makoto Igarashi, Yoshiko Igarashi, Hisato Nagae, Kenji Ichikawa, Tatsuji Yasuda, Takao Koike

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Abstract

Human β2-glycoprotein I (β2-GPI) is involved in cardiolipin (CL) binding of anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE). We examined the inter-species differences of β2-GPl in alternation of CL binding of aCL. β2-GPI preparations were obtained from human, bovine, and rat sera by sequential CL-polyacrylamide affinity, DEAE - cellulose, and anti-human IgG-conjugated Sepharose CL-4B column chromatography, and they had apparent molecular weights of 50, 53, and 55 kDa respectively. Human β2-GPI not only enhanced CL binding by aCL in SLE but also depressed it by those in syphilis. Either bovine and rat β2-GPI exerted no or quite small inhibition of the binding of syphilitic aCL compared with human β2-GPI whereas all three species of β2-GPI generated binding of aCL in SLE to a similar degree. Further, a complete cDNA clone, pβ2-GPI, was isolated from a human hepatoma cell line, HepG2, and its nucleotide sequence was analyzed. The sequences of bovine and rat counterpart molecules (β2-GPI) are highly homologous to that of the deduced sequence, and their corresponding regions are 84.0 and 82.5% identical to the complete domain and to the amino acid sequence 53-326 of human β2-GPI respectively. One of major differences appears at position 154 in human β2-GPI, and might be associated with the inhibitory effect on the binding of syphilitic aCL. The sequencing analysis of these β2-GPI proteins might provide leads to functional sites of domains which would be associated with such serological phenomena.

Original languageEnglish
Pages (from-to)1217-1221
Number of pages5
JournalInternational Immunology
Volume3
Issue number12
DOIs
Publication statusPublished - Dec 1991

Keywords

  • Cardiolipin
  • Syphilis
  • Systemic lupus erythematosus
  • β2-glycoprotein I

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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