Immunoadsorption in Severe C4d-Positive Acute Kidney Allograft Rejection: A Randomized Controlled Trial

Antibody-mediated rejection (AMR) frequently causes refractory graft dysfunction. This randomized controlled trial was designed to evaluate whether immunoadsorption (IA) is effective in the treatment of severe C4d-positive AMR. Ten out of 756 kidney allograft recipients were included. Patients were randomly assigned to IA with protein A (N = 5) or no such treatment (N = 5) with the option of IA rescue after 3 weeks. Enrolled recipients were subjected to tacrolimus conversion and, if indicated, 'anti-cellular' treatment. All IA-treated patients responded to treatment. One death unrelated to IA occurred after successful reversal of rejection. Four control subjects remained dialysis-dependent. With the exception of one patient who developed graft necrosis, non-responders were subjected to rescue IA, however, without success. Because of a high graft loss rate in the control group the study was terminated after a first interim analysis. Even though limited by small patient numbers, this trial suggests efficiency of IA in reversing severe AMR.     

An unexpected complication following immunoadsorption with a staphylococcal protein a column

Extracorporeal immune adsorption with staphylococcal protein A (SPA) columns can remove immune complexes and immunoglobulins in the treatment of a variety of diseases. We present the case of an elderly man with neuropathy associated with monoclonal gammopathy, treated by 3 on-line SPA procedures. At the completion of these treatments his neuropathy relapsed, progressing to near-total paralysis. Return to a baseline clinical status required several months. The reason for this severe relapse is not clear. Possible explanations include SPA activation of T-lymphocytes, with release of gamma interferon and increased antigen recognition, or removal of an anti-idiotype control mechanism. We advise caution in the application of immunoadsorption to conditions in which it has not yet been evaluated. © 1992 Wiley-Liss, Inc.     

Immunoadsorption therapy for paraneoplastic syndromes

Paraneoplastic neurologic syndromes associated with systemic cancer are being increasingly recognized. Although these syndromes are thought to be immunologically mediated treatment with steroids, immunoglobulin and plasmapharesis has been disappointing. Based on our preliminary experience with the treatment of 6 cases of paraneoplastic neurologic syndromes with protein A immunoadsorption, an institutional, open-arm treatment protocol was established. Since our original report we have treated an additional 7 patients with this method. The 13 cases were accrued over a 2 year period and included 10 women and 3 men with an average age of 63. The paraneoplastic syndromes included 6 cases of cerebellar degeneration, 3 cases of opsoclonus/myoclonus, 3 cases of encephalomyelitis and 1 case of Lambert Eaton myasthenic syndrome. Primary cancers included 4 cases of small cell lung cancer, 2 cases of breast cancer, 2 cases of lymphoma and 1 each of acinic cell cancer, cholangiocarcinoma, Merkel cell cancer, pancreatic adenocarcinoma and rectal cancer. Anti-neuronal antibody status, cerebrospinal fluid and neuroimaging studies as well as cancer staging and treatment protocols were reviewed. Neurologic syndromes were clinically separated into component symptoms and signs for assessment of treatment effect. The treatment goal was a total of 6 sessions of protein A immunoadsorption given twice weekly. Twelve of 13 patients completed therapy and one patient developed cutaneous vasculitis during the second session with termination of treatment. Of the remaining patients 3/12 had a complete response of the primary clinical symptom/sign while 6/12 had a partial response for a total response rate of 9/12 (75%). Toxicity was limited to cutaneous vasculitis in 1 patient and an episode of hemisensory changes in another patient. Current treatment of paraneoplastic neurologic syndromes remains unsatisfactory. Despite the small number of patients in this report, protein A immunoadsorption is a promising therapy which deserves further study in a larger population of patients with paraneoplastic syndromes.     

The use of therapeutic apheresis in cardiovascular disease

In the last few years, therapeutic apheresis (TA) has emerged as a valuable treatment option for certain life‐threatening cardiovascular diseases (CVDs) and for all the cardiac dysfunctions caused by autoimmune or metabolic disorders. Besides the well‐established indications for apheresis treatment, such as familial hypercholesterolaemia, hyperviscosity syndrome and thrombotic thrombocytopenic purpura (TTP), we discuss the novel approaches in the therapy of dilated cardiomyopathy, cardiac failure and some specific syndromes of severe dysfunction occurring after heart transplantation. The rationale for using apheresis in such patients is the contribution in immune modulation that this procedure can undoubtedly provide. The clinical course of TTP has dramatically changed, thanks to the introduction of therapeutic plasma exchange. Low‐density lipoprotein apheresis has been extremely efficacious, safe and suitable for lowering cholesterol levels and can be used even for long‐term treatment. In Waldenström macroglobulinaemia and other hyperviscosity syndromes, plasma exchange has demonstrated to be an efficient tool for reducing blood viscosity and the risk of a consequent cardiac dysfunction. However, TA may induce oxidative injury to erythrocytes, making these cells more prone to haemolysis and causing a significant reduction in their half‐life. Ascorbate administration can be useful to lower the levels of hydrogen peroxide and proinflammatory mediators in patients undergoing apheresis. Further data are needed to support this benefit and to test other potential antioxidant therapies. Many of these therapeutic indications need further studies to be definitively approved, but preliminary data are encouraging.     

Treatment of coagulation inhibitors with extracorporeal immunoadsorption (Ig-Therasorb)

Coagulation inhibitors may occur as alloantibodies in patients with congenital factor deficiencies or as autoantibodies in patients with a previously normal coagulation. We treated 10 patients with factor VIII inhibitors (three haemophiliacs and seven patients with acquired factor VIII inhibitors) and one patient with a factor V inhibitor using extracorporeal immunoadsorption to immobilized antibodies against human immunoglobulins (Ig-Therasorb). The initial inhibitor titre was between 18 BU/ml and 540 BU/ml. Nine patients had signs of bleeding. Eighty-nine immunoadsorption sessions were performed in the 11 patients (8.1 +/- 5.1 per patient), each processing 6980 +/- 880 ml of plasma in 3.8 +/- 0.5 h. The mean reduction of the inhibitor titre was 71.9 +/- 19.4% per session. Serum IgG, IgA and IgM levels decreased by 68.7 +/- 10.1%, 55.7 +/- 12.7% and 48.6 +/- 11.1% respectively. In two haemophiliac patients, an initial titre reduction prior to an immune tolerance protocol was performed. Another haemophiliac patient was treated because of acute cerebral bleeding. In six out of eight patients with acquired inhibitors, a durable elimination was achieved within a median of 18 d. Treatment was safe and well-tolerated and seems to be a promising method in the treatment of patients with coagulation inhibitors, especially when a fast inhibitor titre reduction is necessary.     

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随着血液净化技术的飞速发展,新型吸附材料的不断开发,以及临床治疗的迫切需要,免疫吸附技术日趋完善,其临床应用范围也不断扩大。目前,免疫吸附在各系统自身免疫性疾病、多种难治性疾病和危急重症,特别在重症感染性疾病和多器官功能障碍综合征的治疗中发挥了重要作用。     

蛋白A免疫吸附治疗高致敏肾移植受者1例报告并文献复习

目的肾脏移植的致敏性是目前临床面临的一大难题,高致敏受者接受移植的机会大大减少,我们对1例高致敏受者肾移植围手术期采用蛋白A免疫吸附疗法配合免疫抑制治疗,观察其临床效果,结合文献评估疗效.方法受者采用蛋白A免疫吸附成功进行肾移植病例,同时回顾通过国内外文献检索得到的蛋白A免疫吸附治疗肾移植高致敏受者的病例.结果结合我们目前的病例,分析已被报道的66例(国内30例,国外36例)蛋白A免疫吸附治疗肾移植高致敏受者的病例,发现大部分患者采用了蛋白A免疫吸附可以明显降低IgG、IgM、IgA等,PRA从术前30%～100%降低到术后30%以下,65例成功进行了肾移植.结论 Protein A免疫吸附可以清除体内免疫球蛋白疗效明显,结合免疫抑制治疗使肾移植高致敏受者成功接受肾移植,提高移植肾远期存活率.     

Specific immunoadsorption of pathogenic autoantibodies in pemphigus requires the entire ectodomains of desmogleins

Pemphigus foliaceus (PF) and pemphigus vulgaris (PV) are life‐threatening autoimmune blistering skin diseases. They are characterized by circulating autoantibodies which bind to the ectodomains of desmoglein (Dsg) 1 and Dsg3. These antibodies induce acantholysis in skin and mucous membranes. In severe cases of pemphigus, immunoadsorption is applied to remove total IgG from patient plasma using protein A or other ligands. To develop a specific adsorber for anti‐Dsg antibodies, epitope mapping studies of Dsg1 and Dsg3 ectodomains were conducted. Dsg variants were expressed on the surface of HEK‐293 cells and analysed for reactivity with pemphigus and control sera by indirect immunofluorescence technique. For Dsg1, a construct consisting of domain 1 directly fused to domain 5, seemed to be suitable for specific immunoadsorption of anti‐Dsg1 antibodies. The recognized epitopes were mainly conformation‐dependent. However, adsorption of pemphigus foliaceus IgG using this protein coupled to a Sepharose matrix did not completely remove pathogenicity from the sera, as proven by a keratinocyte dissociation assay. In contrast, full‐length Dsg1 and Dsg3 ectodomains were able to specifically adsorb anti‐Dsg antibodies and to efficiently eliminate pathogenicity. Therefore, the complete and correctly folded ectodomains of both desmogleins are required for therapeutic immunoadsorption.