ROLE OF COMPLEMENT COMPONENTS IN DEFINING THE BENEFICIAL EFFECTS OF PLASMA EXCHANGE IN ORGAN TRANSPLANTATION.

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ROLE OF COMPLEMENT COMPONENTS IN DEFINING THE BENEFICIAL EFFECTS OF PLASMA EXCHANGE IN ORGAN TRANSPLANTATION.
Bela Chauhan Ph.D. , Ralph L. Graff, MD and Anil K. Chauhan, Ph.D. . St. Louis MO, St. Louis University, 63104, Surgery and St. Louis MO, ProGen Biologics, 63021 .

Plasma exchange (PE) is a therapy used for management of organ transplant, its mode of action is poorly understood. Benefits of PE is reported to have come from the removal of cytotoxic antibodies, circulating immune complexes (CICs) and harmful cytokines. We demonstrate for the first time, presence of IgG-CICs, IgM-CICs and complement C3 and C4 bound to CICs in pre and post PE serial samples in a transplant patient. The levels of IgM-CICs after each PE treatment significant dropped with initial drop to 46.36 % and proportional drops with subsequent treatments. The levels of IgG-CICs after first therapy dropped by 30 %, similar decline were observed with subsequent treatments. The amount of C3 fixed to CICs showed much higher reduction (> 60%) after initial two treatments and (30%-42%) with successive treatments, with pre treatment C3 levels of 2.15 ug/ml dropping to 0.53 ug/ml at the end of treatment. Interestingly the drop in concentrations of fixed C4 on CICs was highly significant with an initial drop of 82.6 % and similar declines with subsequent treatments. PE treatment resulted in a decrease of fixed C4 levels of 2.79ug/ml pre-therapy to post therapy level of 0.023ug/ml. We hypothesize that the change in the levels of monomeric vs. complexed globulin dramatically affects the lattice of CICs, altering their complement fixing ability. This change may results in decreased production of anaphylotoxins C3a and C5a, the known potent initiator of inflammatory pathways. It has been recently reported that C5a also regulates the expression of FcgRIIB, the key molecule involved in the Fc mediated inflammatory response. Based on these recent observations it is possible that PE may be modulating inflammatory responses mediated by both complement and Fc receptor pathways.