ANTIPHOSPHOLIPID SYNDROME AND THE IDIOTYPIC NETWORK

To study whether monoclonal anticardiolipin antibodies (aCL), derived from patients with antiphospholipid syndrome (APS), have similar patho genic potential, we have employed an experimental model of antiphospho lipid syndrome. Monoclonal aCL were produced by the combined method of EBV transformation and somatic cell hybridization of lymphocytes, der ived from patients with APS. The monoclonal aCL were used to immunize mice at the footpads and the mice were followed for serological and cl inical manifestations of APS. The monoclonal antibody EY2C9, was found to bind weakly to cardiolipin and other phospholipids (i.e. phosphati dyl-serine, phosphatidyl-ethanolamine and phosphatidyl-inositol). The antibody TM1B9, although derived from a patient with SLE and with seco ndary APS, did not react with phospholipids. Immunization of naive BAL B/c mice with EY2C9 was followed by production of sustained high titer s of antiphospholipid antibodies associated with prolonged activated p artial 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 moder ate titer of antiphospholipid antibodies and did not show prolonged AP TT. The pregnant mice, that were immunized with EY2C9, had increased f etal resorption rate (the equivalent of fetal loss in the human) of 36 .8 +/- 10% (vs. 2 +/- 4% in mice immunized with TM1B9). Our results co nfirm 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 find ings suggest that immunization with antibody, although non-reactive wi th what is thought to be the antigen, but derived from a patient with active disease, can still promote the development of related antibodie s, probably because it has other characteristics of pathogenicity (i.e . idiotype).