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Thromb Haemost 1998; 80(05): 791-797
DOI: 10.1055/s-0037-1615360
Review Article
Schattauer GmbH

The Prevalence of a Non-phospholipid-binding Form of β2-Glycoprotein I in Human Plasma

Consequences for the Development of Anti-β2-glycoprotein I Antibodies
Daniëlle A. Horbach
1   From the Departments of Haematology, The Netherlands
2   From the Departments of Rheumatology and Clinical Immunology, University Hospital Utrecht, The Netherlands
3   From the Departments of Institute of Biomembranes, University Utrecht, The Netherlands
,
Erica van Oort
1   From the Departments of Haematology, The Netherlands
2   From the Departments of Rheumatology and Clinical Immunology, University Hospital Utrecht, The Netherlands
,
Mariëlle J. Tempelman
1   From the Departments of Haematology, The Netherlands
,
Ronald H. W. M. Derksen
2   From the Departments of Rheumatology and Clinical Immunology, University Hospital Utrecht, The Netherlands
,
Philip G. de Groot
1   From the Departments of Haematology, The Netherlands
3   From the Departments of Institute of Biomembranes, University Utrecht, The Netherlands
› Author AffiliationsThis work was supported in part by grants from “The Dutch League against Rheumatism” (NR 642) and “De Trombosestichting Nederland” (No 94.002).
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Publication History

Received 17 March 1998

Accepted after revision 19 July 1998

Publication Date:
07 December 2017 (online)

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Summary

The presence of antiphospholipid antibodies (aPL) is strongly correlated with venous and arterial thrombosis, fetal loss and thrombocytopenia. This relation is called the antiphospholipid syndrome (APS). It is well recognized that thrombosis related aPL are not directed against phospholipids alone, but to phospholipid bound plasma proteins like β2-glycoprotein I (β2GPI). aPL that need β2GPI for the binding to negatively charged phospholipids are called anti-β2GPI-antibodies. Recently, a mutation in the gene encoding β2GPI has been described, which results in an amino acid substitution Trp316 into Ser316. This Ser316-β2GPI did not bind to negatively charged phospholipids. Because only phospholipid bound β2GPI is recognized by human anti-β2GPI-antibodies, it might be argued that individuals carrying the Trp316Ser mutation are protected against the development of anti-β2GPI-antibodies.

To investigate this hypothesis, the prevalence of the Trp316Ser mutation was measured in 170 systemic lupus erythematosus (SLE) patients and in 18 patients with the primary antiphospholipid syndrome (PAPS) and the mutation was correlated with the presence of anti-β2 GPI-antibodies. In the total patient group 1 homozygous patient and 21 heterozygous patients were found. The allele frequency of the mutation in SLE patients with anti-β2GPI-antibodies (0.063) was comparable to that found in SLE patients without anti-β2-GPI-antibodies (0.062). These results indicate that the heterozygous presence of Trp316Ser mutation does not prevent an individual from developing anti-β2GPI-antibodies. We showed that this can be explained by the concentration of Trp316-β2GPI in heterozygous patients, which is far above the minimal β2GPI level necessary for optimal phospholipid binding. In our single patient homozygous for the Trp316Ser mutation no binding of β2GPI to the phospholipid surface was detected and no anti-β2GPI-antibodies were present in the plasma of this patient.

In conclusion, heterozygous Trp316Ser β2GPI persons are not protected against the development of anti-β2GPI-antibodies. To confirm that homozygotes do not develop anti-β2GPI-antibodies a very large population is needed, due to the relatively low prevalence of the mutation.

 

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