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Antiphospholipid syndrome and the idiotypic network

Research Unit of Autoimmune Diseases, Department of Medicine 'B'. Sheba Medical Center, Tel-Hashomer 52621 Israel, and Sackler Faculty of Medicine. Tel-Aviv University, Israel, Department of Cell Biology, Weizmann Institute of Sciences. Rehovot. Israel

M. Blank

Research Unit of Autoimmune Diseases, Department of Medicine 'B'. Sheba Medical Center, Tel-Hashomer 52621 Israel, and Sackler Faculty of Medicine. Tel-Aviv University, Israel

D. Kosashvilli

Research Unit of Autoimmune Diseases, Department of Medicine 'B'. Sheba Medical Center, Tel-Hashomer 52621 Israel, and Sackler Faculty of Medicine. Tel-Aviv University, Israel

K. Ichikawa

Lupus Research Unit. The Rayne Institute, St. Thomas' Hospital, London, UK

M.A. Khamashta

Lupus Research Unit. The Rayne Institute, St. Thomas' Hospital, London, UK

G.R.V. Hughes

Lupus Research Unit. The Rayne Institute, St. Thomas' Hospital, London, UK

T. Koike

Hokkaido University School of Medicine, Sapporo, Japan

Y. Shoenfeld

Research Unit of Autoimmune Diseases, Department of Medicine 'B'. Sheba Medical Center, Tel-Hashomer 52621 Israel, and Sackler Faculty of Medicine. Tel-Aviv University, Israel

To study whether monoclonal anticardiolipin antibodies (aCL), derived from patients with antiphospholipid syndrome (APS). have similar pathogenic potential, we have employed an experimental model of antiphospholipid syndrome.

Monoclonal aCL were produced by the combined method of EBV transformation and somatic cell hybridization of lymphocytes, derived from patients with APS. The monoclonal aCL were used to immunize mice at the footpads and the mice were followed for serological and clinical manifestations of APS.

The monoclonal antibody EY2C9, was found to bind weakly to cardiolipin and other phospholipids (i.e. phosphatidyl-serine, phosphatidyl-ethanolamine and phosphatidyl-inositol). The antibody TM 1B9, although derived from a patient with SLE and with secondary APS, did not react with phospholipids. Immunization of naive BALB/c mice with EY2C9 was followed by production of sustained high titers of antiphospholipid antibodies associated with prolonged activated partial thromboplastin time (APTT) (46.8 ± 5.0 s vs. 22.4 ± 1.7 s, in the non-immunized mice). Mice immunized with TM 1 B9 had a more moderate titer of antiphospholipid antibodies and did not show prolonged APTT. The pregnant mice, that were immunized with EY2C9, had increased fetal resorption rate (the equivalent of fetal loss in the human) of 36.8 ± 10% (vs. 2 ± 4% in mice immunized with TM 1 B9).

Our results confirm that monoclonal aCL, derived from a patient with APS, can have a pathogenic potential, dysregulating the idiotypic network and leading to the development of characteristic signs of APS. Moreover, our findings suggest that immunization with antibody, although non-reactive with what is thought to be the antigen, but derived from a patient with active disease, can still promote the development of related antibodies, probably because it has other characteristics of pathogenicity (i.e. idiotype).

Key Words: anticardiolipin antibodies • autoimmunity • animal model • antiphospholipid syndrome • pathogenic antibodies

Lupus, Vol. 4, No. 3, 204-208 (1995)
DOI: 10.1177/096120339500400307


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