PATHOGENIC NATURAL ANTICARDIOLIPIN ANTIBODIES - THE EXPERIENCE FROM MONOCLONAL GAMMOPATHY

Anti-cardiolipin antibodies (ACA) were detected in 19% of sera from pa tients with monoclonal gammopathies (MG). ACA were purified from the s era of patients with MG. One of the IgG-ACA was found to be monospecif ic with high affinity for cardiolipin, and to carry a pathogenic ACA I d (1.10). Active immunization of naive BALB/c mice with the purified I gG-ACA was followed by production in the mice of sustained high titres of ACA, associated with prolonged activated partial thromboplastin ti me (APTT) (61 +/- 14s versus 31 +/- 2s in control mice; P < 0.001) and thrombocytopenia (468 000 +/- 224 000/mm(3) versus 994 000 +/- 92 000 /mm(3) in controls; P < 0.001). The titres of other autoantibodies (e. g. anti-DNA, anti-histones), although being high after immunization, d ecreased rapidly and were undetected after 1 month following the boost injection. The mice immunized with the IgG-ACA exhibited low fecundit y (36% of mice became pregnant versus 62% observed in the group immuni zed with control IgG). The pregnant mice had increased resorption rate (the equivalent of fetal loss in the human) of 52 +/- 8% (versus 5 +/ - 4% in the control group). The mean (+/-s.d.) embryo and placental we ights in mice with anti-phospholipid syndrome (APLS) were significantl y lower compared with the mice injected with control IgG (682 +/- 304 mg and 102 +/- 12 mg versus 1303 +/- 105 mg and 145 +/- 8 mg, respecti vely; P < 0.001). Serum monoclonal immunoglobulins having autoantibody activity may be regarded as an expansion of clones producing natural autoantibodies. Our results confirm the pathogenic role of natural ACA in the pathogenesis of the anti-phospholipid syndrome.