Differences between human hybridoma platelet-binding antibodies derived from systemic lupus erythematosus patients and normal individuals.
The binding and functional activities of platelet-binding hybridoma autoantibodies from SLE patients were compared with those derived from normal individuals. Twenty-nine SLE-derived hybridoma antibodies and 20 normal-derived hybridoma antibodies were analyzed for binding to glutaraldehyde fixed platelets, dDNA and phospholipids, and for lupus anticoagulant activity. Twenty-four of the 29 SLE-derived antibodies and 9 of the 20 normal-derived antibodies showed one or more activities in these assays. Of the 24 SLE-derived antibodies, 8 (33.3%) were reactive in only one assay (monospecific), while the other 16 (66.7%) had more than one of these activities (polyspecific). In contrast, none (0%) of the 9 normal-derived antibodies with known activities were monospecific, while all 9 (100%) showed polyspecificity. Statistical analyses demonstrated that there was no correlation of anti-DNA activity with anti-platelet and most anti-phospholipid activities for the SLE-derived antibodies, and strong positive correlations between these reactivities for the normal-derived antibodies. Similarly, differences were observed in Western blotting analyses; SLE-derived antibodies bound more specifically to individual platelet proteins than normal-derived antibodies. Moreover, in chromium-51 release assays, all of the SLE-derived platelet-binding antibodies were cytotoxic to platelets, while none of the normal-derived platelet-binding antibodies showed significant cytotoxicity. Our results suggest that hybridoma platelet-binding autoantibodies derived from SLE patients exhibit greater antigen specificity and functional activity than similar antibodies derived from normal individuals.
Meng
Q H
QH
Rheumatic Disease Unit, Montreal General Hospital Research Institute, McGill University, Quebec, Canada.
Rauch
J
J
D000974:Antibodies, Antinuclear; D000918:Antibody Specificity; D001323:Autoantibodies; D001792:Blood Platelets / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D066298:In Vitro Techniques; D016682:Lupus Coagulation Inhibitor; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D016682:Lupus Coagulation Inhibitor