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 TM1B9, 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 TM1B9 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 TM1B9). 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.(ABSTRACT TRUNCATED AT 250 WORDS)