Norbert Braun

Immunoglobulin and Circulating Immune Complex Kinetics During Immunoadsorption onto Protein A Sepharose

Immunoadsorption onto protein A sepharose can be applied to eliminate immunoglobulins, autoantibodies and circulating immune complexes from the circulation. In vivo kinetic studies showed that all IgG subclasses are removed from the patients plasma although IgG3 elimination is variable and dependent on the presence of other immunoglobulins. IgG elimination half time was 4.8 days during intermittent and 2.9 days for daily therapy in the absence of immunosuppression. Autoantibodies and immune complexes can be cleared effectively but administration of intravenous immunoglobulins should be avoided because of competition for protein A binding sites. Redistribution/ denovo synthesis (half time 2.1-8.8 d for IgG 1-4) occurred in the absence of immunosuppression.

Acute effect of rheopheresis on peripheral endothelial dysfunction in patients suffering from sudden hearing loss.

Abstract:u2002 Single low density lipoprotein (LDL) fibrinogen apheresis has shown beneficial effects in the treatment of patients with sudden sensorineural hearing loss (SSHL). Pathophysiologically, a microcirculatory disorder of the inner ear, probably caused by disturbed endothelial function, is discussed as a final common pathway of a variety of SSHL etiologies. Thus, we carried out a prospective pilot study on the efficacy of Rheopheresis on vascular function in these patients, embedded into an ongoing randomized controlled multicenter trial investigating the efficacy of Rheopheresis for the treatment of SSHL. Potential modulation of systemic endothelial dysfunction by Rheopheresis was examined by measuring flow‐associated vasodilatation of the brachial artery (according to the criteria of the American College of Cardiology) in a small group of patients suffering from SSHL (Nu2003=u20036, 5m/1f, mean age 56u2003±u200311u2003years) within the last 3u2003days. At baseline, five of the six patients with acute hearing loss showed endothelial dysfunction as evidenced by diminished flow‐mediated vasodilatation (FMDu2003<u20035%). After a single Rheopheresis treatment, flow‐mediated vasodilatation improved significantly (from 3.9u2003±u20033.6% to 7.2u2003±u20032.4%, Pu2003=u20030.05, meanu2003±u2003SD, two‐sided paired T‐test). This was paralleled by a reduction in fibrinogen (364u2003±u2003216u2003mg/dL to 142u2003±u200396u2003mg/dL, Pu2003=u20030.03), total cholesterol (228u2003±u200323 to 98u2003±u200310, Pu2003<u20030.0001) and LDL cholesterol levels (153u2003±u20038u2003mg/dL to 83u2003±u200323u2003mg/dL, Pu2003<u20030.01). Based on this case series we conclude that single Rheopheresis treatment might have an acute beneficial effect on endothelial dysfunction in patients suffering from SSHL.

Successful transplantation of highly selected CD34+ peripheral blood stem cells in a HLA-sensitized patient treated with immunoadsorption onto protein A.

BACKGROUNDnHaploidentical bone marrow transplantation with preexisting anti-HLA antibodies is associated with a high risk of graft failure.nnnMETHODSnA 27-year-old female patient with chronic myeloid leukemia and evidence of several osseous chloromas had no suitable matched bone marrow donor, and fluorescence cytometric cross-match (FCXM) revealed antibodies against donor-specific HLA-molecules. Immunoadsorption onto staphylococcal protein A was applied to remove these antibodies, and peripheral stem cell transplantation was performed from her haploidentical sister after a negative FCXM was documented after immunoadsorption and conditioning treatment.nnnRESULTSnFCXM for donor lymphocytes and stem cells remained negative throughout the posttransplant period, and engraftment of donor cells was documented on day +69.nnnCONCLUSIONnImmunoadsorption onto protein A should be considered in stem cell transplantation even from an haploidentical donor where anti-HLA antibodies and a positive FCXM are documented.

Antioxidative Treatment Retards Progression of Idiopathic Membranous Nephropathy

Dear Sir,Idiopathic membranous glomerulone-phritis (MGN) is the most frequent cause ofnephrotic syndrome in adult patients withglomerular disease. Although alkylating sub-stances may be effective in controlling pro-teinuria, treatment is still controversial [1],and patients with advanced disease mightnot respond to this treatment [2].A male 21-year-old bank clerk developedMGN in 1996 unresponsive to a 3-monthcourse of high-dose prednisolone therapy, re-sistant to a 6-month course of alternativechlorambucil and prednisolone therapy, andshowing no effect of ciclosporin A for anoth-er 9months. Despite continuous angioten-sin-converting enzyme A inhibitor treatmentand low-protein diet, he showed persistentnephrotic-range proteinuria above 10g/24h,while total serum protein remained !5g/dland albumin !2.0g/dl. A steady increase ofserum creatinine to 3.5mg/dl was noted.Clinical, immunological, bone marrow, andradiological examinations excluded second-ary causes of MGN. We stopped ciclosporinand repeated the renal biopsy. Membranousnephropathy stageIII according to Churgand Ehrenreich with chronic focal tubuloin-terstitial fibrosis was confirmed.In experimental passive Heymann ne-phritis, it was recently demonstrated thatlocal accumulation of reactive oxygen spe-cies might represent a major effector mecha-nism in MGN. In passive Heymann nephri-tis rats, the local production of reactive oxy-gen species results in an increase of break-down products of peroxidative damaged lip-ids, expressed as malondialdehyde equiva-lents, in glomerular cells and within glomer-ular basement membranes. The inhibition oflipid peroxidation by pretreatment of PHNrats with the antioxidant probucol resultedin an approximately 85% reduction of pro-teinuria and in a markedly reduced malon-dialdehyde content in renal tissue. Theamount of lipid peroxidation was related todamage of the filtration barrier with genera-tion of membrane attack complex C5b-9 andsubsequent proteinuria [3].On the basis of these results, we suggest-ed an antioxidant therapy. The patient con-sented to a therapeutic trial with anti-oxidants (1,200mg ascorbic acid, 600IU

Therapeutic Immunoadsorption—its Role in Clinical Practice

Extracorporeal immunoadsorption onto staphylococcal protein A replaces conventional plasmapheresis because its elimination efficiency is higher while less adverse reactions are seen. Experience in immunoadsorption is limited to specialized centers although recent technical developments make the procedure simple and safe to use. During a workshop held in Munich, September 1996, the application of immunoadsorption in various diseases was discussed. Goodpastures syndrome, acquired autoimmune coagulopathy, HLA-sensitized transplantation and treatment-resistant life-threatening autoimmune diseases were accepted indications for immunoadsorption. Immunoadsorption in other immunoglobuline and immune complex mediated diseases is still under discussion.

The German Glomerulonephritis Therapy Study: 10 Years of Controlled Randomized Trials for the Treatment of Idiopathic Glomerulonephritis

The German Collaborative Glomerulonephritis Therapy Study, which celebrated its 10th anniversary in 1996, has collected data on more than 1,000 patients with biopsy-proven glomerulonephritis. 929 patients could be evaluated and 500 were treated according to at least one of various protocols developed for a randomized controlled trial. Current results show that prednisolone is effective in minimal-change nephropathy, and in combination with other immunosuppressants it can reduce proteinuria in individual cases of focal and segmental glomerulosclerosis, membranous glomerulonephritis and nephrotic IgA nephropathy. The majority of tested treatment protocols did not prove to be superior to symptomatic therapy for long-term outcome.