Lessons from experimental APS models.
Several animal models for antiphospholipid syndrome (APS) have been reported in the literature. These experimental models have contributed significantly in resolving enigmas in this multisystemic disease. We, and others have previously shown the pathogenicity of anticardiolipin (aCL) antibodies in pregnancy outcome. We have expanded our studies to show the pathogenicity of aCL antibodies in renal dysfunction and neurological and behavioral impairments in animals with experimental APS. Animals immunized with aCL or with the cofactor beta2GPI developed clinical manifestations of APS, including fetal loss, thrombocytopenia and neurological and behavioral dysfunction, along with elevated levels of aPL antibodies. In another animal model, peripheral blood lymphocytes (PBLs) derived from APS patients could initiate APS manifestations with renal dysfunction in SCID mice. A unique in vivo model for thrombus formation was recently established to show the pathogenicity of aPL in thrombosis associated with APS. Histological evaluation of affected tissues derived from animals or from patients with APS have pointed to common mechanisms underlying APS, showing mainly thrombotic changes accompanied by mild inflammatory reaction.
Shoenfeld
Y
Y
Research Unit of Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel.
Ziporen
L
L
D000026:Abortion, Habitual / Q000209:etiology; D019264:Adoptive Transfer / Q000009:adverse effects; D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000276:immunology / Q000633:toxicity; D016736:Antiphospholipid Syndrome / Q000150:complications / Q000276:immunology* / Q000473:pathology; D001327:Autoimmune Diseases / Q000150:complications / Q000276:immunology* / Q000473:pathology; D001777:Blood Coagulation; D004195:Disease Models, Animal; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006351:Heart Valves / Q000473:pathology; D006801:Humans; D007105:Immune Complex Diseases / Q000209:etiology / Q000276:immunology; D007114:Immunization; D007674:Kidney Diseases / Q000209:etiology / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D001523:Mental Disorders / Q000209:etiology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D016513:Mice, SCID; D009422:Nervous System Diseases / Q000209:etiology / Q000276:immunology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology; D011256:Pregnancy Outcome; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000209:etiology / Q000276:immunology / Q000473:pathology; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D006023:Glycoproteins; D053482:beta 2-Glycoprotein I