A kinetic study of erythrocyte-DNA/anti-DNA immune complex association and dissociation reactions in systemic lupus erythematosus.
Decreased binding capacity of the erythrocyte complement receptor (RBC CR1) in systemic lupus erythematosus (SLE) may contribute to abnormal handling of circulating immune complexes in these patients. Decreased numbers of RBC CR1 have been reported in SLE, but, since binding is a function of both receptor number and receptor binding kinetics, we measured kinetic parameters for the interaction of complement (C) containing [3H]DNA:anti-DNA immune complexes (IC) with normal control (NC) and SLE RBC. Experiments were performed at five temperatures ranging from 7-37 degrees C. The parameters measured included: (1) the maximum quantity of DNA:anti-DNA:C which could bind per RBC, S; (2) the association rate constant, ka, for the binding of DNA:anti-DNA:C to RBC; (3) the dissociation rate constant, kd, for the dissociation of bound DNA:anti-DNA:C IC from RBC; (4) the steady-state constant, Kss (ka/kd); and (5) the energies of activation for association, Eaa, and dissociation, Ead. Although the relative amount of bound DNA:anti-DNA:C per RBC was significantly decreased in SLE patients compared to NC (P less than 0.001), the mean values for Kss, ka, kd, Eaa and Ead did not differ significantly between the two groups. These data suggest the following: (1) RBC CR1 binding and dissociation of DNA:anti-DNA:C are consecutive reactions resulting in steady-state concentrations of free and RBC-bound IC; (2) at steady-state times, the ratio of RBC bound to unbound DNA:anti-DNA:C are governed by kinetic factors; (3) since the binding kinetics of SLE and NC RBC are not significantly different, the decreased binding activity described by other investigators can only be due to a decreased number of CR1 per RBC; and (4) values for Eaa and Ead suggest that the rate-determining steps in IC association with and dissociation from RBC involves making and breaking of hydrogen bonds.
Meryhew
N L
NL
Department of Medicine, University of Minnesota Medical School, Minneapolis.
Westling
P R
PR
Eerdmans
M E
ME
Janecek
E J
EJ
Runquist
O A
OA
D000974:Antibodies, Antinuclear / Q000378:metabolism; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D004247:DNA / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008956:Models, Chemical; D011951:Receptors, Complement / Q000378:metabolism; D013816:Thermodynamics
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D011951:Receptors, Complement; D004247:DNA