Efficacy of immunoadsorption to reduce donor-specific alloantibodies in kidney-transplant candidates.

OBJECTIVES: We implemented a desensitization program at our center to enable transplant in kidney-transplant candidates who have a living human-leukocyte antigen-incompatible (HLAi) donor. We report on the efficacy of semispecific immunoadsorption to allow HLAi kidney transplant in 6 highly sensitized patients. MATERIALS AND METHODS: We chose immunoadsorption as the apheresis technique coupled to hemodialysis as a means to decrease donor-specific alloantibodies in kidney transplant candidates submitted to a pretransplant desensitization program to remove detrimental antibodies. RESULTS: Six highly sensitized kidney-transplant patients (5 females), awaiting their first (n = 1) or second (n = 5) kidney transplant from a living donor, were enrolled in this desensitization program. They had 1 (n = 2), 2 (n = 1), 3 (n = 2), or 4 (n = 1) donor-specific alloantibodies; their mean fluorescent intensities at predesensitization ranged from 1200 to 19 000. Each patient underwent between 10 and 16 immunoadsorption sessions. At the time of transplant, donor-specific alloantibodies were undetectable in 2 patients (A24, DR3); donorspecific alloantibodies decreased by > 50% in 8 patients (A11, B44, DR3, DR11, DQ3 thrice, DQ5); donor-specific alloantibodies remained unchanged in 2 patients (B50, DR13); and mean fluorescent intensities were slightly increased in 2 patients (Cw6, DQ8). In the analysis of final outcomes, 2 patients experienced no rejection (1 experienced donor-specific alloantibody elimination, and 1 experienced a > 50% decrease in donor-specific alloantibodies). One patient presented with acute antibody-mediated rejection, which required immunoadsorption sessions and eculizumab therapy (donor-specific alloantibodies between 5000 and 19 000). Two patients presented with subacute antibody-mediated rejection; 1 was treated by plasmapheresis/rituximab therapy, and the other was treated with plasmapheresis/ methylprednisolone pulses. Another patient presented with chronic antibody-mediated rejection, which was treated unsuccessfully with plasmapheresis/rituximab; a tentative of rescue therapy with eculizumab was attempted without success. CONCLUSIONS: Desensitization of the humanleukocyte antigen using this immunoadsorption procedure effectively reduced or eliminated donorspecific alloantibodies in 71% of patients undergoing kidney transplant, at the time of transplant.

Efficacy and safety of tandem hemodialysis and immunoadsorption to desensitize kidney transplant candidates.

OBJECTIVES: We conducted a desensitization program in our center in patients undergoing kidney transplant for end-stage renal disease. These patients had a living-donor either ABO incompatible and/or human-leukocyte antigen-incompatible. The safety and efficacy of this program were evaluated. MATERIALS AND METHODS: A pretransplant desensitization program relies on immunosuppressants and apheresis to remove detrimental antibodies. We chose immunoadsorption as the apheresis technique, and coupled this with hemodialysis in a tandem procedure. RESULTS: We report on the efficacy of this new method in 120 procedures performed in 20 patients (14 ABO incompatible, 6 ABO incompatible/human leukocyte antigen-incompatible). The tandem procedure was well tolerated, and saved time compared with conducting sequential immunoadsorption and hemodialysis (6 h vs 10 h). The tandem procedure was associated with significantly decreased isoagglutinin titers and donor-specific alloantibodies (assessed by mean fluorescence intensity). Dialysance was effective (183, 102-264). The biochemical and hematologic parameters were similar to those observed after a conventional hemodialysis session, with the exception of protidemia; this might be related to some degree of albumin loss during the immunoadsoprtion procedure. The posttransplant events included 1) one ABO incompatible / human leukocyte antigenincompatible patient with vein thrombosis and ultimate kidney loss; 2) two patients with steroidsensitive cellular acute rejection; and 3) two patients with acute antibody-mediated rejection, which was successfully treated with apheresis and steroid pulses, plus rituximab in one and eculizumab in the other. CONCLUSIONS: We conclude that the tandem immunoadsorption-hemodialysis procedure is efficient at desensitizing patients with end-stage renal disease who are candidates for a living ABO incompatible and/or human leukocyte antigenincompatible donor-kidney transplant.

Neurologic diseases of the central nervous system with pathophysiologically relevant autoantibodies--perspectives for immunoadsorption.

Immediate antibody elimination, pulsed induction of antibody redistribution, and immunomodulation are major forces of efficacy of therapeutic apheresis (i.e. plasma exchange [PE] or immunoadsorption [IA]) for autoimmune neurologic disorders. Therapeutic apheresis can offer rapid response for severe acute neurologic symptoms, and stable rehabilitation in long-term clinical courses being refractory to drug based strategies or complicated by drug side effects. PE or IA in these situations must be considered as part of multimodal or escalating immune treatment strategies in combination or in competition with intravenously administered immunoglobulins (ivIg), corticosteroids, the full spectrum of immunosuppressive drugs, and bioengineered antibodies. Selective IA is increasingly replacing PE due to its superior safety profile and increasing knowledge on pathogenic relevance of autoantibodies. Recent experiences in autoimmune diseases of the central nervous system, e.g. multiple sclerosis, neuromyelitis optica, and autoimmune encephalitis confirmed this concept.

Immunoadsorption in steroid-refractory multiple sclerosis: clinical experience in 60 patients.

BACKGROUND: Multiple sclerosis (MS) is the most common autoimmune inflammatory demyelinating disease of the central nervous system with a frequently relapsing or progressive course. For steroid-resistant relapse, plasma exchange (PE) has been established as guidelines-recommended treatment option. While PE is a non-selective extracorporeal blood purification process with elimination of plasma and subsequent substitution, immunoadsorption (IA) is a selective technique for the removal of autoantibodies and immune complexes with less adverse effects. So far there are only few reports on the treatment of MS by IA. The aim of this retrospective study was to assess the efficacy and safety of IA as an escalation therapy in MS patients. PATIENTS AND METHODS: A total of 60 patients with steroid-refractory MS relapse were treated by IA and analyzed retrospectively. Patients received six standardized IA sessions using a non-regenerable tryptophan immunoadsorber, at average 58 days after first indications of relapse. The treated plasma volume was two liters per IA session. Outcome was measured as improvement in relapse symptoms. From the pilot phase of the study comprising the first fourteen patients, detailed neurological examinations before and after IA such as Expanded Disability Status Scale (EDSS), Functional System Score (FS) and visual acuity are reported. Of the following 46 patients, only qualitative data regarding the therapeutic success, and in addition clinical data on tolerability, are presently available. RESULTS: In 53 of 60 patients clinically relevant improvement of the main symptom of MS relapse was noted after IA, there was no change in six patients, deterioration in one. This corresponds to a response rate of 88%. Symptomatic improvement was first registered on average after the third IA. 87.5% of patients could be treated through a peripheral venous access. Only 12.5% needed a central venous catheter. In four of 396 single treatments (1%) significant complications occurred, mild side effects or discomfort were registered 16 times (4%). If peripheral venous access was chosen, missed puncture or puncture hematoma occurred in 22 cases (5.5%). CONCLUSION: Immunoadsorption for the treatment of steroid-refractory MS relapse is safe and effective. The response rate was 88% and non-inferior to previous results with plasma exchange. Due to good tolerability, the treatment with immunoadsorption, which is usually possible through a peripheral venous access, can be performed on an outpatient basis.

Immunoadsorption in steroid-refractory multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disorder, with involvement of both the humoral and cellular components of the immune system. The use of plasma exchange (PE) in steroid-refractory relapses has become an integral part of national and international guidelines for the treatment of steroid-resistant relapses of MS with an efficacy of 40-70%. So far, 6 studies of immunoadsorption (IA) treatment in different forms of MS have been published, 4 of them in steroid-refractory MS relapses. These 4 studies revealed a significant clinical improvement in 73-85% of patients with steroid-refractory MS relapses. However in MS patients with non-active relapsing-remitting or secondary progressive course, there was no clinical improvement. Despite the limited number of patients and studies, these data suggest a reasonably similar efficacy of IA in the treatment of steroid-refractory MS relapses compared to PE. More prospective trials are needed to confirm and extend these results.

Immunoadsorption for connective tissue disease.

Distinct connective tissue diseases (CTD's) such as systemic lupus erythematosus (SLE), systemic sclerosis, mixed connective tissue disease as well as dermato- and polymyositis comprise a group of diseases, where autoantibodies are not merely indicators of autoimmune disease, but also play an relevant role in the underlying pathogenicity. This knowledge led to the development of antibody targeting therapies using rituximab or belimumab. Upon this, therapeutic plasma exchange, and more recently immunoadsorption (IAS) have been successfully applied to remove pathogenic autoantibodies under various conditions in some of these CTD's. While the technique of IAS is superior to plasma exchange in regard to specificity and efficacy, the clinical use of IAS in CTD's is currently restricted to a small proportion of clinical situations with either refractory disease or the necessity to avoid aggressive immunosuppressive regimens. Despite the presence of a large number of case series and few controlled trials using IAS, there is a need for further prospective randomized trials to clearly define the role of IAS in these CTD's.

Long-term effects of a multimodal approach including immunoadsorption for the treatment of myasthenic crisis.

A multimodal treatment protocol with immunoadsorption (IA) as the central element was used in the treatment of myasthenic crisis (MC). Fifteen patients with MC were treated in repeated, uninterrupted 7-day cycles until mobilization with: (i) large-volume IA using an antihuman-IgG adsorber, days 1-5; (ii) intravenous immunoglobulin substitution (0.3-0.5 g/kg body weight [BW]/day), days 5-7; and (iii) immunosuppression with cyclophosphamide (1-2 mg/kg BW/day) and prednisolone (0.5-1 mg/kg BW/day), until remission. Patients required a median of 8 days of mechanical ventilation, 12 days in the intensive care unit, and 35 days of hospitalization. Functional improvement compared to their precrisis condition was attained by 14 of 15 patients. MG severity score improved by a mean of 10 points, quality of life score by 9.8 points, and Karnofsky index by 29 points in 14 of 15 patients. Improvements remained stable and no further crises occurred during long-term follow-up, which averaged 4.4 years. No fatalities due to MC occurred. The results demonstrate that our protocol is a potent therapeutic approach in the treatment of MC.

A novel immunoadsorbent for rheumatoid arthritis therapy--preparation and efficacy evaluation.

AIM: To develop a novel immunoadsorbent for rheumatoid arthritis (RA) therapy. METHODS: A RA immunoadsorbent was developed by binding heat-aggregated human IgG(HAHIgG) to porous agar gel beads. Its adsorption capacity for rheumatoid factors (RFs), storage stability and blood compatibility were evaluated. RESULTS: The coupling yield of HAHIgG on the carrier was 6.0 mg/g wet gel. Saturation adsorption capacity of the adsorbent for IgMRF, IgGRF and IgARF were 3400, 2240 and 2400 IU/g, respectively. The adsorbent can be stored at 4 degrees C for three months without significant variance in its activity. Its fine permeability and hemocompatibility were demonstrated by extracorporeal hemoperfusion on rabbits. CONCLUSION: HAHIgG/agar gel is a safe and effective immunoadsorbent for RA therapy, its potential clinical use is promising in the future.

A multi-centre trial of pollen-tyrosine adsorbate.

We report the results of a multi-centre trial involving 433 hay fever patients treated in 1975 with a 3-injection tyrosine-adsorbed vaccine containing glutaraldehyde-modified grass pollens and cultivated rye. Despite the high pollen counts recorded in Germany in 1975, treatment was considered to be effective in 73 per cent of the patients, irrespective of their age, sex or past history. Side effects were normally mild although the incidence of local reactions was relatively high. Only six patients discontinued treatment due to untoward reactions and there were no cases of anaphylactic shock. This paper adds further evidence to support the view that this vaccine offers a safe, effective and convenient method of treatment for grass pollen allergy.