Five years' experience at one centre with protein A immunoadsorption in patients with deleterious allo/autoantibodies (anti-HLA antibodies, autoimmune bleeding disorders) and post-transplant patients relapsing with focal glomerular sclerosis

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Abstract
Protein A is extracted from a strain of Staphylococcus aureus and binds specifically to the constant domains of immunoglobulins and possibly to fibronectin. It has already been shown that concentrations of all IgG isotypes (except IgG3) are efficiently decreased by immunoadsorption (IA) on protein A linked to sepharose beads. This system has been developed by Cobe-Excorim Co. to either remove IgG in some instances where they will be harmful, i.e. allo- and autoantibodies inducing pathological conditions (autoimmune diseases, haematological disorders with allo/autoantibodies, anti-HLA antibodies in sensitized patients awaiting organ transplantation) or treat several immunological diseases with unknown pathogenesis. In our unit, 20 patients with high titres of anti-HLA panel-reactive antibodies, four patients with haematological disorders (haemophilia with anti-VIII antibodies and Glanzmann diseases) and three patients with post-transplant focal glomerular sclerosis (FGS) underwent IA over the past 5 years. Infectious complications were not observed after IA and the procedure was always well tolerated. In spite of the use of adjunctive immunosuppressive therapy with prednisone and cyclophosphamide, and although the reduction in serum IgG was close to 90%, the de novo synthesis of allo- and autoantibodies was important after IA procedures. In the cases of removal of anti-HLA antibodies, patients with a pre-IA antibody titre which was >1:128 clearly did not benefit from the technique and other immunological criteria were not predictive of efficacy. Fourteen patients were transplanted, four with a well-matched kidney with both pre- and post-IA negative cross-matching, and 10 with a positive historical cross-match with the donor. The graft survival was 80% in the first group, contrasting with 40% in the second. In haematological bleeding disorders, most of the patients showed a substantial reduction in their auto/alloantibodies with consequent alleviation of their bleeding status enabling further surgical management. Here again, the rebound of antibody synthesis was poorly controlled by conventional immunosuppression. In the cases of recurrent FGS where the pathogenesis implicates an immediate alteration of glomerular permeability by plasma factor(s), IA consistently decreased proteinuria, although the effect remained limited in time with a return to the pre-IA albuminuria within 2 months. We conclude that IA is a safe procedure. Its efficacy remains variable and a better control of antibody synthesis rebound by new drugs needs to be reached.

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