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Background: Plasma exchange (PE) and immunoadsorption (IA) are alternative treatments of steroid-refractory relapses of multiple sclerosis (MS) or neuromyelitis optica (NMO)., Methods: Adverse events and neurological follow-ups in 127 MS- (62 PE, 65 IA) and 13 NMO- (11 PE, 2 IA) patients were retrospectively analyzed. Response was defined by improvements in either expanded disability status scale (EDSS) by at least 1.0 or visual acuity (VA) to 0.5, confirmed after 3 and/or 6 months., Results: Hundred and forty patients were included in safety analysis, 102 patients provided sufficient neurological follow-up-data. There were no significant differences between IA and PE in side effects (3.9% vs 3.6%, P = .96) or response-rate (P = .65). Responders showed significant lower age (P = .02) and earlier apheresis-initiation (P = .01). Subgroup-analysis confirmed significant lower age in patients with relapsing-remitting MS (RRMS) /clinical isolated syndrome (CIS)., Conclusion: IA and PE seem equally safe and effective in steroid-resistant MS- or NMO-relapses. Early apheresis and low patient age are additional prognostic factors., (© 2019 Wiley Periodicals, Inc.)

Autoimmune bullous diseases (AIBD), including pemphigus, bullous pemphigoid, epidermolysis bullosa acquisita, mucous membrane pemphigoid, and pemphigoid gestationis, pose significant therapeutic challenges, especially in pregnant and post-partum breastfeeding patients or those planning to conceive. Data on the safety and efficacy of therapeutic interventions during the perinatal period are lacking because randomized controlled trials are typically not performed in this setting. However, many of the treatments for AIBD are also used in other diseases, so data can be extrapolated from studies or case reports in these other patient populations. It appears that many of the treatments for AIBD can adversely affect the fetus or neonate, and alterations in immune status caused by pregnancy-associated hormonal changes can negatively impact disease control. This article summarizes and weighs the risks and benefits of the various agents used to treat AIBD during pregnancy. We also present the available information on lactation as well as effects on male fertility.

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare paralyzing inflammatory neuropathy with probably autoimmune origin. While plasma exchange (PE) constitutes a first-line treatment option for CIDP, there is only little known about the efficacy and safety of immunoadsorption (IA), a more selective apheresis procedure with assumed better tolerability., Methods: In this prospective-randomized pilot trial, patients were randomly assigned to receive 6 sessions of PE (n = 10) or IA (n = 10) treating equal plasma volumes. To evaluate efficacy, we calculated the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score and the Medical Research Council (MRC) sum score at baseline (V1), after completion of 6 sessions (V2) as well as 4 weeks after completion (V3) in 9 patients per group (1 patient in each group did not complete follow-up). We additionally assessed safety and tolerability of treatments by monitoring adverse event and blood parameters., Results: With IA, 6 out of 9 (66.7%) patients improved clinically, whereas with PE, 4 out of 9 (44.4%) patients improved, most of them immediately with completion of the apheresis treatment series. There was one adverse event (AE) out of 52 treatment sessions for the 9 patients in the IA group. In the PE group of 9 patients, there was 1 AE out of 51 sessions and a trend of greater fibrinogen reduction. No severe AE occurred in either group., Conclusion: The results of this pilot study suggest that IA is at least equally effective and safe compared to PE in CIDP patients., (© 2017 Wiley Periodicals, Inc.)

Atopic dermatitis (AD) is a common disease affecting up to 10-20% of the population with the largest disease burden in childhood. Treatment options include basic emollient treatment, topical as well as systemic immunosuppressants. The pathogenesis is complex and among various triggers, genetic predisposition and immunological alterations contribute to development of disease. Atopy is common in patients with AD and many patients have high levels of Immunoglobulin E (IgE), some of which recognizes exogenous or auto/self-allergens. Treatment options targeting IgE such as specific immunotherapy against e.g. house dust mites or using anti-IgE antibodies (omalizumab) showed variable results that were not convincing. We now review recent data on the application of unspecific and IgE-selective immunoadsorption (IA) in AD. All in all, 53 patients have been treated with non-specific pan Ig IA and 28 patients with IgE-selective IA. Side effects were rarely seen. The efficacy of IgE depletion was generally high (<∼80%) for each IA cycle, but transient and lasted only a few days/weeks. Of note, disease activity appeared to improve in almost all cases and lasted for several weeks. Although the evidence is still weak, these case studies suggest that IgE depletion in AD is effective and helped control the disease. The mechanism of action is not understood yet. Future controlled trials are needed to validate this observation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Pemphigus vulgaris is a chronic autoimmune disease characterized by blisters and erosions forming in the mucous membranes and the skin. Many patients are severely impaired by pain, weight loss and increased risk of infections. The disease is mediated by specific autoantibodies directed against desmogleins that contribute to connect keratinocytes in the epidermis. Autoantibody deposition in the skin causes inflammation and intraepidermal akantholysis. The concentration of autoantibodies in serum correlates with disease activity. Therefore, the removal of autoantibodies by immunoadsorption is a targeted therapeutic intervention for patients with pemphigus vulgaris., Patients and Methods: A total of 9 patients with pemphigus vulgaris resistant to the standard treatment regimen were treated by immunoadsorption using the TheraSorb™-Ig adsorber system and analyzed retrospectively. Patients received immunoadsorption on two or four consecutive days. Cycles were repeated every two or four weeks, respectively. Treatment was performed for a mean period of 17.5 months (range 6-26). Outcome was measured as improvement in clinical disease analyzed by the investigators global assessment and the reduction of autoantibodies in serum measured by indirect immunofluorescence and ELISA. Tolerability of treatment by patients was evaluated using a visual analog scale., Results: Retrospective analysis of 9 patients consecutively treated by immunoadsorption revealed an 80% reduction of the autoantibody concentration in serum after 6 months of treatment, led to a clinical improvement of disease in combination with classical immunosuppression. Steroid consumption could be reduced by 50% after 30 and 75% after 90 days. Therapy resulted in a total response rate of 89%, with 56% of patients reaching partial and 33% complete remission. The bi-weekly treatment regimen resulted in effective improvement of disease and was in favor to the 4-weekly regimen by the subjective judgment of tolerability by the patients., Conclusion: Immunoadsorption for the treatment of pemphigus vulgaris is safe and effective. The good tolerability of a bi-weekly treatment regimen shown here might be a valuable therapeutic option in further studies defining the optimal frequency of immunoadsorption required in treatment of pemphigus., (Copyright © 2017. Published by Elsevier B.V.)

Introduction: Immunoadsorption (IA) is increasingly used instead of plasma exchange due to lower risk of side effects and a higher selectivity. As a consequence of the reduction of immunoglobulins (Ig), the rate of infectious complications might increase in those patients. We therefore aimed to investigate the infection rate following IA without intravenous IG (IVIG) substitution in our apheresis center, where patients do not receive IVIG on a regular basis., Material and Methods: We conducted a retrospective analysis of the IA treatments performed between 2010 and 2015 without IVIG substitution and collected data on patient age, diagnosis, number of IA treatments, serum levels of Ig, total protein, albumin, C-reactive protein (CRP) and infectious complications that occurred within 2 months after the IA treatment cycle., Results: A total number of 52 patients (27 females) received at least 5 IA sessions using the following adsorbers: TheraSorb™-Ig (n = 3), TheraSorb™-Ig flex (n = 44), TheraSorb™ Ig pro (n = 1) and TheraSorb™-IgE (n = 5). The median number of treatment sessions was 8.8 [range 5-16], the median IgG reduction was 82 [11-99] %. Serum albumin was decreased by 8%. The median CRP levels remained normal until the end of therapy and within 2 months after that (3.10 and 4.30 mg/L respectively). Only 4 patients had infections (7.7%). Three of them received additional immunosuppressive therapy., Conclusions: Immunoadsorption leads to a significant reduction of IgG. CRP as inflammatory marker is not affected. Even without substitution of IVIG the complication rate directly linked with IA is low and questionable., (Copyright © 2017 Elsevier B.V. All rights reserved.)

ABO incompatible (ABOi) organ transplantation requires pre-transplant reduction of the recipient's IgG and IgM isoagglutinin titer against the donor to prevent hyperacute rejection. Over the past four years we primarily used unspecific IgG immunoadsorption (IA) for this purpose and combined this selectively with membrane filtration (IAc) to reduce IgM isoagglutinines. In patients with an initial IgG titer against donor below 1:64, plasma exchange (PE) was initiated. In this retrospective analysis covering January 2012 to August 2015 we compared how efficiently IgG and IgM isoagglutinines in a total of 22 ABOi kidney transplant recipients were reduced by either IA (n = 75 sessions), IAc (n = 14 sessions) or PE (n = 40 sessions). Median pre-treatment IgG isoagglutinin titers were 32 (4-4096) while IgM titers were 16 (1-256) respectively. Mean IgG reduction by either treatment modality was 1.3 ± 0.9 (IA), 1.8 ± 1.0 (IAc) and 2.6 ± 1.3 (PE) titer steps per session (p < 0.001 IA vs. PE; p < 0.04 PE vs. IAc). Mean IgM reduction was 0.6 ± 0.6 (IA), 1.8 ± 0.8 (IAc) and 2.4 ± 1.9 (PE) titer steps (p < 0.001 for both IA vs. PE and IA vs. IAc). Our data indicate that PE efficiently removed IgG- and IgM isoagglutinines. By processing only half the plasma volume per treatment PE was twice as effective as IA in terms of IgG-type isoagglutinin removal in our patient group. This is best explained by the presence of soluble AB0 antigens in the FFP used as plasma replacement. These advantages in efficacy have to be weighed against the potential hazards of PE. Combination of IA and plasma filtration effectively removes IgM-type and even enhances net IgG-type isoagglutinin elimination compared to IA alone. When trying to avoid PE, combined application of IA and IAc is a possible and effective way to reduce isoagglutinin titers before ABOi transplantation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Autoimmune encephalitis is a severe inflammatory disorder of the brain. The discovery that several non-infectious forms of encephalitis are associated with autoantibodies was a breakthrough in the care of this previously untreatable group of patients. The correlation of antibody type and titer with pattern and severity of symptoms was essential for the initiation of immunotherapies. First line therapy consists of steroids, intravenous immunoglobulins, plasma exchange or immunoadsorption. Rapid elimination of autoantibodies using selective immunoadsorption and avoiding the disadvantage of plasma substitution is a pathophysiologically guided therapeutic approach, and has been proven to be an effective therapeutic option as part of multimodal immunotherapy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Transplanting immunized patients requires immunological monitoring in the pretransplant phase to follow reduction of donor specific HLA antibodies (DSA) after Staphylococcus aureus protein A (SPA) immunoadsorption (IA) or therapeutic plasma exchange followed by IVIG and Rituximab administration. Pretreatment aims to significantly reduce DSA strength. The Tissue Typing Lab at Aarhus University Hospital performs immunological monitoring of approximately 150 kidney transplantation patients per year from two transplant centers. From 2012 to 2013, we experienced seven patients desensitized using SPA IA, initially presenting negative cytotoxic complement dependent (CDC) T-cell crossmatches but positive B and T cell flowcytometric crossmatch, who despite significant DSA reduction developed weakly positive CDC T-cell crossmatch shortly prior to transplantation. We hypothesised that leached SPA during IA could be the cause, as the complication was not observed in patients who received plasma exchanges. We found that the positive CDC was not donor specific and SPA column material incubated with control serum reproduced a positive CDC T-cell crossmatch. Finally, we detected leached SPA in one of the patient samples using a highly sensitive time-resolved fluorescent assay. In conclusion, the results emphasize the importance of carefully considering CDC crossmatch results subsequent to IA, before a planned transplantation is either postponed or cancelled. J. Clin. Apheresis 32:163-169, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Prevention of IgE-binding to cellular IgE-receptors by anti-IgE (Omalizumab) is clinically effective in allergic asthma, but limited by IgE threshold-levels. To overcome this limitation, we developed a single-use IgE immunoadsorber column (IgEnio). IgEnio is based on a recombinant, IgE-specific antibody fragment and can be used for the specific extracorporeal desorption of IgE., Objective: To study safety and efficacy of IgEnio regarding the selective depletion of IgE in a randomized, open-label, controlled pilot trial in patients with allergic asthma and to investigate if IgEnio can bind IgE-Omalizumab immune complexes., Methods: Fifteen subjects were enrolled and randomly assigned to the treatment group (n=10) or to the control group (n=5). Immunoadsorption was done by veno-venous approach, processing the twofold calculated plasma volume during each treatment. A minimum average IgE-depletion of 50% after the last cycle in the intention-to-treat population was defined as primary endpoint. Safety of the treatment was studied as secondary endpoint. In addition, possible changes in allergen-specific sensitivity were investigated, as well as clinical effects by peak flow measurement and symptom-recording. The depletion of IgE-Omalizumab immune complexes was studied in vitro. The study was registered at clinicaltrials.gov (NCT02096237) and conducted from December 2013 to July 2014., Results: IgE immunoadsorption with IgEnio selectively depleted 86.2% (±5.1% SD) of IgE until the end of the last cycle (p<0.0001). Removal of pollen allergen-specific IgE was associated with a reduction of allergen-specific basophil-sensitivity and prevented increases of allergen-specific skin-sensitivity and clinical symptoms during pollen seasons. IgEnio also depleted IgE-Omalizumab immune complexes in vitro. The therapy under investigation was safe and well-tolerated. During a total of 81 aphereses, 2 severe adverse events (SAE) were recorded, one of which, an episode of acute dyspnea, possibly was related to the treatment and resolved after administration of antihistamines and corticosteroids., Conclusions: This pilot study indicates that IgE immunoadsorption with IgEnio may be used to treat patients with pollen-induced allergic asthma. Furthermore, the treatment could render allergic patients with highly elevated IgE-levels eligible for the administration of Omalizumab and facilitate the desorption of IgE-Omalizumab complexes. This study was funded by Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: ABO blood group-incompatible kidney transplantation (ABOiKTx) outcomes are good, but complications are more common than in conventional transplantation. Regimens that use extracorporeal antibody removal therapy (EART) and enhanced immunosuppression are guided by titration of ABO blood group antibodies (using hemagglutination [HA] dilution assays), and these assays vary significantly in performance between centers. This study aims to describe the differences in titer measurement and the effect on clinical practice and outcomes., Study Design and Methods: This multicentre, prospective cohort study of 100 ABOiKTx recipients assessed treatment and outcome data, including HA assay results measured retrospectively in a single central laboratory., Results: Patient and allograft survival at 1 year was 99% and 94%, respectively. There were significant differences in the number of pretransplantation EART sessions in centers undertaking plasma exchange (PEx), compared with immunoadsorption (IA) (median, 6 vs. 4 sessions; p = 0.007). The pre-EART HA titer in both groups was the same when centrally assayed. The local HA assay used to guide treatment yielded significantly higher titers in centers undertaking PEx compared with IA (median, 128 vs. 32; p < 0.005). Patients undergoing PEx rather than IA were significantly more likely to suffer postoperative hematoma (12.9% vs. 1.8%; p = 0.05) or any perioperative collection requiring drainage (19.4% vs. 3.6%; p = 0.02)., Conclusion: The colinearity of HA assay sensitivity with the receipt of PEx and EART limits some conclusions regarding the likely direction of causation. However, the association of differences in clinical practice with recognized perioperative complications of ABOiKTx identifies targets for further investigation and quality improvement., (© 2016 AABB.)

The combined use of immunoadsorption (IA) and membrane filtration (MF) may markedly enhance removal of IgM and complement component C1q, supporting its use as an element of recipient desensitization in antibody-incompatible transplantation. However, coagulation factor removal may contribute to altered hemostasis, posing a risk of bleeding in the perioperative setting. This secondary endpoint analysis of standard coagulation assays and rotational thromboelastometry (ROTEM®) was performed in the context of a randomized controlled crossover study designed to assess the effect of combined IA (GAM-146-peptide) and MF on levels of ABO antigen-specific IgM. Fourteen patients with autoimmune disorders were randomized to a single treatment with IA+MF followed by IA alone, or vice versa. MF was found to markedly enhance fibrinogen depletion (57% vs. 28% median decrease after IA alone, P < 0.001), whereby four patients showed post-treatment fibrinogen concentrations below 100 mg dL(-1). In support of a critical contribution of fibrinogen depletion to impaired coagulation, extrinsically activated ROTEM(®) analysis revealed a marked reduction in fibrinogen-dependent clot formation upon IA+MF (59% median decrease in FIBTEM mean clot firmness (MCF) as compared to 24% after IA alone, P < 0.001). Moreover, the addition of MF led to a substantial prolongation of activated partial thromboplastin time, possibly due to depletion of macromolecular coagulation factors contributing to intrinsically activated coagulation. Our study demonstrates substantial effects of combined IA+MF on clot formation, which may be mainly attributable to fibrinogen depletion. We suggest that the use of combined apheresis in the setting of transplant surgery may necessitate a careful monitoring of coagulation., (© 2015 Wiley Periodicals, Inc.)

Patients with atopic dermatitis (AD) tend to have greatly elevated levels of serum immunoglobulin E (IgE). However, the role of IgE in the pathogenesis of AD is debated. This investigator-initiated open-label pilot study evaluates an anti-IgE-treatment approach by combining extracorporeal immunoadsorption and anti-IgE antibody omalizumab in 10 patients with severe, therapy-refractory AD. IgE levels decreased after immunoadsorption and decreased continuously in all patients during anti-IgE therapy. The reverse trend was observed during 6 months follow-up without treatment. In parallel with these observations, an improvement in AD was observed during the treatment period, with aggravation during follow-up. Further research is needed, based on the principle of reducing IgE levels in order to improve clinical symptoms, using a combination anti-IgE treatment approach, adjusted according to IgE levels.

In recent years, immunoadsorption is increasingly recognized as an alternative treatment approach replacing therapeutic plasma exchange in a variety of neurological disorders. While most experience is based on the application of single-use tryptophan adsorbers, less data exists on the application of more efficient regenerating adsorber columns. We here report the systematic use of a regenerating adsorber system in various neurological indications such as multiple sclerosis, encephalitis, myasthenia gravis and chronic inflammatory demyelinating polyneuropathy, providing the expected treatment success in regard to reduction of immunoglobulins and antibody clearance, together with a low rate of adverse events. As it has been shown for single-use columns before, immunoadsorption with regenerating adsorbers can be successfully applied in disorders without known specific antibodies such as multiple sclerosis. Regenerating systems offer the perspective to provide a more efficacious long term treatment perspective for such patients., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Diabetes mellitus (DM) is a risk factor for death from heart failure (HF) in patients with dilated cardiomyopathy (DCM) but DM patients are less eligible for heart transplantation (HTx) and DM is a risk factor for death also after HTx. New therapies are therefore necessary to improve survival of diabetic DCM patients. Immunoadsorption (IA) can improve heart function in DCM but its usefulness for therapy of DM-associated DCM is unknown. We assessed this aspect., Methods: Cardiac function and HTx-free survival were evaluated in diabetic HTx-candidates with DCM who underwent IA (Globaffin(®), a broadband-immunoadsorber containing synthetic peptide-GAM(®)) in 6/2003-6/2012 (follow-up 1-10 yrs). Non-diabetic HTx-candidates with DCM who received IA in the same time-period served as controls. Before and after IA patients were tested for serum β1-autoantibodies (β1-AABs)., Results: We evaluated 31 patients with and 31 without DM. Before IA there were no differences between the 2 groups in LV size, LVEF and β1-AAB levels. However, DM patients were older, their HF duration was longer and their peak oxygen-uptake was lower (p < 0.005). During the 1st post-IA year in both groups there was a decrease in LV size and improvement in both LVEF and NYHA-class (p < 0.05). Post-IA 3-year HTx-free survival and prevalence of responders to IA in patients with and without DM was 81.3 ± 8% and 78.4 ± 8%, respectively and 73.3% and 67.7%, respectively. Post-IA 3-year freedom from β1-AAB reappearance in patients with and without DM reached 72.1 ± 9.0% and 71.1 ± 8.6%, respectively., Conclusions: IA improves heart function, exercise tolerance and Tx-free survival in patients with DM-associated end-stage DCM. Our results also suggest that IA can delay HTx-listing, improve survival on HTx lists and even spare some diabetic patients from HTx, benefits of particular importance for these patients who are at high risk for pre-HTx and post-HTx mortality., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: A total plasma exchange was the first extracorporeal method to treat patients with severe hypercholesterolemia. But in the long run it has several disadvantages. The newer lipoprotein apheresis (LA) methods claim to be more selective with respect to the removal of atherogenic lipoproteins and thus are supposed to avoid an additional protein loss., Methods: We wanted to compare the effect of these methods on serum protein concentrations (total serum protein, albumin, proteins measured with electrophoresis, immunoglobulins, fibrinogen, transferrin, and ferritin) which were checked before and after a single LA session in 75 patients. All patients underwent active LA treatment using 6 different LA methods (HELP, TheraSorb(®) LDL, DALI, Lipidfiltration, Liposorber D, MONET). Post-apheresis concentrations were corrected for changes in hematocrit., Results: The slightest impact on total serum protein was observed with the whole-blood methods. Liposorber D showed the least reduction of albumin levels. All LA methods had a small effect on alpha1-globulins and beta-globulins, but alpha2-and gamma-globulins were reduced to a different extent. A major effect was seen on the immunoglobulins when filtration methods were applied. In the patients treated with MONET, both pre- and post-apheresis Immunoglobulin M concentrations were below the normal range. HELP and the filtration methods significantly reduced the fibrinogen concentrations. The filtration methods also decreased ferritin levels but the post-apheresis ferritin levels were still in the normal range., Conclusion: All LA methods had an influence on protein concentrations. At present, these findings will not yield an individualized treatment approach for any selective LA method due to the lack of prospective comparative studies. At minimum, special attention should be paid to protein concentrations in patients suffering from protein deficit., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Lipoprotein apheresis and immunoadsorption methods have a firm place among therapeutic approaches in order to treat disorders of lipoprotein metabolism or anti-body induced diseases. The extracorporeal treatment is associated with adverse effects, we wanted to report the Dresden experience., Methods: In this study we retrospectively analyzed the adverse events of several lipoprotein apheresis and immunoadsorption methods at the Apheresis Center in Dresden (Germany). We carefully looked into all available documents. The first extracorporeal lipoprotein apheresis was performed in 1990 and the first extracorporeal immunoadsorption was executed in 1995. Throughout the 23 years study period, 10 different methods were employed in treating 268 patients for a total of 25,293 treatments., Results: Adverse events of varying severity occurred in 1948 of the treatments (7.7%). We subdivided them into mild (61.3% no treatment was necessary), moderate (37.0% oral medication or infusion was given) and severe (1.7% emergency hospitalization was necessary). Therapy had to be stopped prematurely in 1.5% of the treatments. We compared adverse events profiles among the different methods and evaluated for differences by gender. Females were found to have a significantly higher risk of adverse events than male patients. In males, the rate of adverse events ranged from 3.3% (Liposorber(®) D) to 11% (Therasorb™ Ig); in females the minimum rate was 7.8% (DALI) and the maximum 30% (rheopheresis). Adverse events were evenly distributed between the ages of 30-69, the age range at which most of the therapies were performed. We also found that all methods had a higher rate of adverse events during the first year of treatment. Puncture problems and hypotension were the most common adverse events., Conclusion: It can be stressed that in general the extracorporeal methods used can be regarded as safe., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Therapeutic apheresis has reached an important value in the treatment of neurologic disorders. In the indication of acute relapses of inflammatory demyelinating conditions plasma exchange (PE) is currently mentioned in guidelines in adults and children. Immunoadsorption (IA) is a younger but more selective apheresis method. Compared to PE, data on IA in these indications are less substantiated. Hitherto existing studies indicate IA as effective and safe with similar response rates versus PE. Our own study of 140 adult patients treated with PE or IA in steroid refractory multiple sclerosis or neuromyelitis optica affirm previous findings showing no significant difference in efficacy and treatment safety. Analogue to adult patients, children seem to benefit from apheresis therapy in steroid resistant inflammatory demyelinating conditions but their treatment implies certain challenges concerning physiology, anatomy and psychological aspects necessitating a multidisciplinary therapeutic setting., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: In Acquired Haemophilia (AH) autoantibodies against blood coagulation factors, mainly FVIII, inhibit the blood coagulation cascade. The clinical symptoms can vary from minor to severe life threatening bleedings. At present it is unclear if the intensity of the treatment needs to be adapted to the severity of the disease., Methods: The clinical data and long term outcome from 20 patients suffering from minor severe AH were summarized. Bleedings requiring no blood transfusions were defined as less severe. In case of FVIII concentration <5% an immunosuppressive treatment (IT) consisting of cyclophosphamide 1-2 mg/kg BW/d and/or prednisolone 1-2 mg/kg BW/d was initiated., Results: IT induced complete remission (CR) in only 40% of patients (8/20) after a mean time of 133.4 d (±90.7 d). Treatment associated severe side effects occurred in all patients. 15 patients required a factor substitution therapy due to proceeding bleedings. In 7 patients a partial remission (PR) of AH could be achieved; bleedings progressed in 5 of them and they underwent successfully second line immunoadsorption-based protocol. The inhibitor titer differed statistically significant between CR and PR with a mean of 3.7 BU vs. 16 BU. 5 patients had a fatal outcome mainly due to severe disease associated co morbidities., Conclusion: Immunosuppressive treatment failed in nearly a half of AH patients. Mortality was with 25% still high. The majority of patients required an intense long-term IT and developed severe treatment related side effect. Immediate start of IT did not control bleeding. In consequence, less severe AH also should be treated with a more rigorous regime because the occurrence of minors bleedings at initial presentation is not a predictive of clinical outcome. An Immunoadsorption-based protocol should be considered first line or even as a salvage strategy., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Background: Immunoadsorption (IAS) and therapeutic plasma exchange (TPE) are considered safe although fibrinogen is removed. To date no comparison of fibrinogen reduction and associated risk of bleeding in apheresis exists., Methods: Retrospective analysis of TPE, three IAS adsorbers, and combined TPE/IAS regarding fibrinogen reduction and bleeding incidence in 67 patients (1,032 treatments)., Results: TPE and TPE/IAS reduced fibrinogen by 64 ± 11% and 58 ± 9%, leading to concentrations <100 mg/dl in 20 and 17% of treatments, respectively. IAS decreased fibrinogen less than TPE (26 ± 6%, p < 0.0001), resulting in fibrinogen concentrations <100 mg/dl in 1% of treatments. The processed volume correlated with reduction in TPE (r = 0.64, p < 0.01), but not in IAS. Bleeding occurred in 1.3% (IAS), 2.3% (TPE) and 3.1% (TPE/IAS) of treatments., Conclusion: Hypofibrinogenemia occurs in 20% of patients after TPE and TPE/IAS, but rarely after IAS. IAS removes fibrinogen independently of volume processed. Overall, bleeding is rare in apheresis., (© 2014 S. Karger AG, Basel.)

Background: ABO-incompatible renal transplantation (ABOi-RTx) following preconditioning with immunoadsorption (IA) and rituximab is a promising approach to facilitate living-related RTx. However, clinical experience is limited in pediatric patients., Methods: Three patients underwent living-related ABOi-RTx in our center. Preoperative IA was performed six, ten and 11 times in patient one, two and three, respectively, to achieve isoagglutinin titers of ≤1:8 on the day of transplantation; rituximab was administered once. The immunosuppressive regimen further comprised tacrolimus, mycophenolate, methylprednisolone and basiliximab; immunoglobulin G (IgG) was infused on the day of ABOi-RTx., Results: All three patients achieved normal renal function within 2-6 days post-RTx. Major postoperative bleeding occurred in two patients, with one requiring repeated blood transfusions and the other a surgical revision 4 h after RTx, despite local citrate anticoagulation use during the preoperative IA procedures in the latter patient. A pyelonephritis-associated increase of the isoagglutinin IgG/IgM titers to 1:64/1:128 led to a biopsy-proven acute humoral rejection in the third patient, which was treated successfully with plasma exchange and methylprednisolone pulses. The estimated glomerular filtration rate at 18, 8 and 23 months post-RTx was 96, 52 and 74 ml/min/1.73 m(2), respectively., Conclusions: ABOi-RTx can successfully be performed in pediatric patients after preconditioning with quadruple immunosuppression, rituximab and IA. Caution is required regarding bleeding complications, which are most likely due to the unspecific binding of coagulation factors during repeated IA.

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., (Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Myasthenic crisis is the most serious life-threatening event in Myasthenia gravis patients, affecting up to 27% within the first two years after onset of disease. Extracorporeal removal of circulating autoantibodies against the nicotinic acetylcholine receptor (AChRAb) by methods of therapeutic apheresis, e.g. plasma exchange (PE) and immunoadsorption (IA) had been demonstrated as effective treatment especially in acute situations of myasthenic crisis. However, controlled data comparing clinical safety and efficacy of both methods in a clinical study were not available. Here the results of a prospective randomized controlled clinical trial are presented, investigating 19 patients with myasthenic crisis, who were randomized to receive either PE (n = 10) or IA (n = 9) in addition to combined drug treatment. Patients received 3 to 5 (mean 3.5 for PE, and 3.4 for IA) treatments over a period of 7 days with a predefined treatment volume of 1.5 l plasma (i.e., 20-25 ml/kg plasma representing 0.5-0.6 patients' plasma volumes). Clinical courses were monitored using disease specific clinical scores. After initiation of IA or PE the mean value of Myasthenia scores decreased equally until Day 14 of the post-treatment phase. Patients from both treatment groups improved to a stable clinical status of Oosterhuis Classes 1 and 2. Substantial reduction of AChRAb was documented after each session of PE or IA. In the treatment period 16 adverse effects (seven serious adverse events, SAE) in the PE and 10 (1 SAE) in the IA group were observed. In conclusion, IA proved to be equally effective compared with PE treatment in patients with myasthenic crisis. Three to five treatment sessions using low plasma volume dosage of 20-25 ml/kg were adequate to improve clinically relevant symptoms significantly in most patients., (Copyright © 2011 Wiley Periodicals, Inc.)

Objectives: The objective of this study was to investigate functional effects of immunoadsorption (IA) in patients with chronic nonfamilial dilated cardiomyopathy (DCM) regarding clinical and humoral markers of heart failure., Background: IA has been shown to induce early hemodynamic improvement in patients with nonfamilial dilated cardiomyopathy (DCM)., Methods: We performed IA using protein A agarose columns on five consecutive days in 51 patients with chronic DCM, congestive heart failure of NYHA class ≥ II, left ventricular ejection fraction ≤50%, and mean time since initial diagnosis of 5.0 ± 5.8 years., Results: Immediately after IA, immunoglobulin G (IgG) decreased by 89.4% and IgG3 by 66.7% (both P < 0.0001). Median NT-pro BNP was reduced from 1230.0 ng L(-1) at baseline to 829.0 ng L(-1) after 6 months (P < 0.0001). Also mean left ventricular ejection fraction (LVEF) was significantly improved (26.3% ± 9.4% to 28.7% ± 11.4% after 6 months, P = 0.016) and LVEF improved ≥5% (absolute) in 21 of 51 (41.2%) patients. After 6 months, bicycle spiroergometry showed a significant increase in exercise capacity from 82.0 ± 30.8 Watts to 93.1 ± 34.3 Watts (P = 0.008) while VO2max rose from 15.0 ± 4.1 to 16.4 ± 4.8 mL min(-1) kg(-1) (P = 0.01)., Conclusions: In this study, on heart failure patients with nonfamilial DCM, IA therapy significantly improved clinical and humoral markers of heart failure severity. These promising results may be due to the selected study population, with a shorter disease duration and the higher amount of IgG 3 reduction. Future blinded prospective multicenter studies are necessary to identify those patients that benefit most., (Copyright © 2010 Wiley-Liss, Inc.)

There is increasing interest from neurologists to use therapeutic apheresis in autoimmune neurologic diseases due to growing knowledge of pathogenic relevance of autoantibodies. Developments in that field have been summarized in this review focusing on German guidelines and recent results from clinical research. Therapeutic apheresis can offer a therapeutic armamentarium with rapid response for severe acute neurologic symptoms, and a drug-free option for clinical courses being refractory to drug based strategies or complicated by drug side effects. Plasma exchange (PE) as the classical method has become part of current guidelines within basic and escalating immunomodulatory treatments of autoimmune neurologic diseases, and in daily practice gets increasingly replaced by selective immunoadsorption (IA) due to its equivalent efficacy in combination with a superior safety profile. Therapeutic effects of PE and IA in autoantibody mediated diseases can be attributed to 3 major mechanisms: immediate intravascular reduction of (auto-)antibody concentration, pulsed induction of antibody redistribution, and subsequent immunomodulatory changes. 5 treatments over a period of 8-10 days seem to be an appropriate regimen to restore neurologic function in acute flares or relapses of autoimmune neuropathies, e.g. myasthenic crisis, Guillain-Barré-syndrome, and steroid refractory relapse of multiple sclerosis. Especially in MS a better understanding is needed, who are the best candidates for IA., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

In acquired haemophilia (AH) healthy humans can suddenly develop severe bleeding due to autoantibodies (inhibitors) against clotting factors, especially factor VIII. The mortality rate of 21 % is considerable, and standardized treatment protocols have not been developed due to the low disease frequency (1-4 per million). Major goals of treatment are the control of bleeding events and rapid inhibitor elimination. Conventional treatment regimens induce immune tolerance via long-term immunosuppression with success rates between 52% and 82%. However, treatment related mortality can rise to 39%. Lack of complete remission, advanced age, underlying malignancies and infections related to immunosuppressive therapy are regarded as principal risk factors for death. The modified Bonn-Malmö Protocol (MBMP), an immune tolerance protocol consisting of antibody depletion through immunoadsorption, i.v. immunoglobulin treatment, immunosuppression and high dose FVIII supplementation, achieves rapid and safe control of acute bleeding. In the largest published single centre study of high risk patients with AH, we previously demonstrated that complete remission (CR) can be achieved in 88.5% of all patients (54/61) within a median time of 3.9 wks (range: 3.2-4.5 wks) and in 97% (54/56) of AH patients without cancer as an underlying condition. Those 5 patients, who suffered also from cancer, achieved partial remission (PR). Mortality or severe treatment-related side effects were not observed. This study confirmed that MBMP is a safe and effective treatment with a high curative potential for severe AH. However, the severity of bleeding, and therefore the cost-effectiveness of the approach, needs to be considered when initiating this treatment protocol., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

In the Czech Republic the therapy of severe familial hypercholesterolemia (FH) by extracorporeal elimination using LDL-apheresis (immunoadsorption) and hemorheopheresis is concentrated into one center. The authors evaluate the long-term therapy (3-12 years, median 7,25) in 12 patients with FH - 3 homozygous, 9 heterozygous; Fredrickson type IIa, IIb (treated: 9 by LDL-apheresis and 3 by hemorheopheresis). Immunoapheretic interventions decrease LDL-cholesterol, ApoB and even Lp(a) by about 82 +/- 1; 73 +/- 13; 82 +/- 19 %, respectively. Selected non-invasive methods are important for a long-term and repeated follow-up. Carotid intima-media thickness showed improvement or stagnation in 75% of the patients. The level of some adhesive molecules, cytokines, endoglin and some coagulation functions were measured, but no universally accepted biomarkers informing of the actual activity of the disease were found to predict and plan the therapy. A program for procedure planning with the use of Microsoft® Excel for Windows® was developed. In summary, LDL-apheresis and hemorheopheresis substantially lower LDL-cholesterol in FH. Our experience with long-term therapy also shows good tolerance and a small number of complications (5,6% of clinically irrelevant side-effects). Hemorheopheresis may improve blood flow in microcirculation in familial hypercholesterolemia and also in some other disorders of microcirculation., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Efficient modes of extracorporeal blood purification are available today for apheresis treatment of progressive atherosclerosis, autoimmune disease, or for improving hemorheology. Advanced technology and sophisticated care render apheresis treatment selective, safe and tolerable. Our task is to constantly update indications for apheresis based on best evidence available and good clinical practice, as well as, to determine how apheresis therapy can be made available to those in need or with otherwise refractory disease. Presenting examples of lipid apheresis, rheopheresis, or immunoadsorption for treatment of hypercholesterolemia, hyperlipoproteinemia (a), acute hearing loss, refractory or exacerbating multiple sclerosis, we highlight real world obstacles for implementation of treatment, resulting in still too many patients with proven or recommended indication left untreated. Based on the experience of the largest apheresis center in Germany, with more than 3,300 treatments per year, we depict the necessary structure for identification of patients, defining indication, referral, implementation of therapy, and reimbursement. Apheresis is unfamiliar to most patients and many practitioners or consultants. Nephrologists, performing >90% of apheresis treatments in Germany, have to form a network for referral comprising all regional care-givers, general practitioners as well as the respective specialists (mainly, cardiologists, endocrinologists, diabetologists, ORL specialists, neurologists, ophthalmologists, or rheumatologists), and insurances or other cost-bearing parties for offering a scientifically approved therapeutic regimen and comprehensive care. We have realized this concept in a high volume apheresis center acting in a closely knit network characterized by an unrelenting effort at ongoing medical education. As a consequence, we include approximately 10 times more patients with appropriate diagnoses in our apheresis program as compared to the national average., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Pathogenic autoantibodies (Abs) are a hallmark of SLE and their rapid removal is beneficial in active SLE. Immunoadsorption (IAS) is effective in removing serum levels of all classes of immunoglobulin (Ig), immune complexes (IC) and anti-dsDNA Abs and appears superior to plasmapheresis with respect to side effects. IAS can be performed with different columns, which use different ligands to bind their target. In particular, high affinity columns are in the focus of interest. Their ligands are either sheep IgG directed against human Ig (Ig-column, Ig-Therasorb®), or staphylococcal Protein A (ProtA-column, Immunosorba®), or the synthetic peptide Gam146 (GAM-column, Globaffin®). In our experience Ig-columns have been effective in treating active renal SLE. However, no analysis has so far been published on which column type should be preferred in treating SLE patients., Patients and Methods: Among our SLE patients maintained on prolonged IAS therapy, we identified those with stable renal SLE and low to moderate disease activity who were successfully treated by using Ig-columns. Six of these patients were switched to ProtA-columns, keeping the rest of the protocol and the medication constant. In addition, two patients were switched from Ig- to GAM-columns., Results: All types of columns significantly lowered the serum levels of IgG, IgM, and anti-dsDNA Abs. Disease activity was constantly low before and after the switch, as were parameters of renal function. In addition, patients with highly active disease were effectively treated when ProtA- (n=6) or GAM-columns (n=1) were used as first-line extracorporeal treatment., Conclusion: Our data demonstrate that all columns are adequately effective in controlling key parameters of SLE. Thus, it is not the type of the ligand, but only the outcome, i.e. the successful removal of Ig, IC, and (auto-) Abs that is required for controlling SLE activity., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Autoimmune bullous diseases are a heterogeneous group of disorders that can be subdivided according to the level of split formation in the intraepidermal blistering pemphigus diseases and subepidermal bullous disorders, latter including pemphigoid diseases, epidermolysis bullosa acquisita, and dermatitis herpetiformis. In the majority of autoimmune bullous disorders, disease activity can be sufficiently controlled by systemic corticosteroids in combination with further immunosuppressants/immunomodulants such as dapsone, doxycycline, methotrexate, azathioprine, or mycophenolate mofetil. In contrast, in pemphigus, mucous membrane pemphigoid, and epidermolysis bullosa acquisita, treatment is challenging and only in a minority of patients, conventional immunosuppressive therapy induces clinical remission. Since only a few years ago, only cyclophosphamide and high-dose intravenous immunoglobulin were available as potent second-line therapies. Meanwhile, immunoadsorption and the monoclonal anti-CD20 antibody rituximab have been established as further therapeutic options. Here, both conventional therapies and novel treatment regimens for autoimmune blistering diseases are discussed.

This non-randomized open clinical study investigated the safety and efficacy of extracorporeal fractionated plasma adsorption using the Oncosorb immune adsorption column. The column selectively bound soluble tumor necrosis factor receptors 1 and 2 (sTNF-R1 and sTNF-R2) and soluble interleukin-2 receptors (sIL2-R) by lowering plasma levels in patients with metastatic cancer. Nine patients (three men and six women; mean age 48 years, aged 41-68 years) with metastatic cancer received at least 12 immune adsorption procedures. Thrice-weekly immune adsorption separated a low molecular weight (150 000 D) plasma fraction from the patients' blood, passing the plasma fraction through the column in an extracorporeal plasma perfusion circuit. Respective plasma receptor mean concentrations before and after 167 procedures were: sTNF-R1: 1936 +/- 788 pg/mL before treatment vs. 1312 +/- 989 pg/mL after treatment; sTNF-R2: 3140 +/- 1173 pg/mL before treatment vs. 1816 +/- 1 +/- 1677 pg/mL after treatment (P < 0.01 for each inhibitor). Mean reductions in sTNF-R1 (48%), sTNF-R2 (55%), and sIL2-R levels (72%) were observed for treatments 3-12 (P < 0.001). Clinical findings indicated tumor inflammation and necrosis in most patients. Side-effects were low-grade fever, flu-like symptoms; tumor pain and redness, warmth, tenderness, and edema. The column demonstrated safety and efficacy in lowering plasma sTNF-R1, sTNF-R2, and sIL2-R levels. Minor clinical adverse effects common to the use of extracorporeal devices were seen.

Background: Immunoadsorption (IA) is occasionally applied in patients with acute relapses of multiple sclerosis (MS). This pilot study was undertaken to determine whether IA might help in secondary progressive and relapsing-remitting multiple sclerosis., Design: IA was performed at 1-week intervals in 12 patients with secondary progressive or relapsing-remitting MS. These patients had an extended disability status scale (EDSS) score of 4.5-7 and an EDSS increase of 0.5 within 6 months before inclusion in the study despite conventional drug therapy. The change in the EDSS and that in the MS functional composite (MSFC) score, which consisted of quantitative tests of arm function, ambulation, visual acuity and cognition, served as the primary outcome variables, which were measured at baseline and at 3, 6 and 12 months. Changes in quality of life and cerebral lesions by magnetic resonance imaging (MRI) were also assessed at baseline and after the last immunoadsorption (month 3)., Results: A significant reduction of the median EDSS change was observed after the treatment period, which reversed 3 months after the immunoadsorptions had been stopped. Ten of 12 patients remained stable during the first year of follow-up with no significant changes of the MSFC scores. No significant changes in magnetic resonance imaging T2-hyperintense brain lesions or in the number of gadolinium-positive lesions and in the patients' quality of life were observed. Western blot analyses demonstrated a reduction of serum myelin-specific antibodies, which were collected in the adsorber eluates., Conclusions: Removal of immunoglobulins, including myelin-specific antibodies by immunoadsorption, seems to delay disease progression as defined by EDSS, MSFC and MRI, while the patients' quality of life did not deteriorate.

Background: Immunoadsorption is increasingly used to treat antibody-mediated autoimmune diseases. To prevent microbial growth during storage, reusable protein A-Sepharose gel columns are primed with ethyl mercury thiosalicylate (thiomersal, 0.1% solution) and rinsed with phosphate buffer before use. In this study, we tested the hypothesis of systemic mercury exposure in protein A immunoadsorption., Methods: Whole blood mercury levels were measured by atomic absorption spectroscopy before and after protein A immunoadsorption (11 patients, 26 treatments), anti-IgG immunoadsorption (eight patients, 13 treatments) and LDL apheresis (DALI and Therasorb systems; nine patients, 14 treatments)., Results: Patients treated with protein A immunoadsorption had significantly elevated baseline mercury levels compared with the other groups, which were not different from healthy controls. Following protein A immunoadsorption, mercury levels increased from 5.9+/-1.4 microg/l (mean+/-SEM, normal, <5 microg/l) to 32.3+/-5.7 microg/l, P<0.001). In one intensively treated patient, acute neurological toxicity developed at a mercury level of 107 microg/l. Symptoms abated slowly and did not recur after switching to a thiomersal-free system and chelation therapy. No mercury release to patients occurred in anti-IgG immunoadsorption or LDL apheresis treatments., Conclusion: This preliminary report suggests that protein A immunoadsorption columns primed with thiomersal during storage may cause a sustained increase of systemic mercury concentrations, which exceed current safety recommendations in a proportion of patients. Considering the potential for mercury-induced toxicity, every effort should be undertaken to reduce systemic mercury exposure, either by adding chelators to the rinsing solution or ideally by replacement of thiomersal.

Objective: Vasculitis is a rare complication of immunoadsorption treatment with staphylococcal Protein A (Prosorba column). The prevalence, clinical characteristics, pathophysiology, treatment, and outcome of vasculitis secondary to immunoadsorption treatment is not known., Methods: The authors describe a 57-year-old woman with rheumatoid arthritis (RA) resistant to methotrexate and etanercept, who developed severe leukocytoclastic vasculitis after the 9th weekly treatment with Prosorba column. She developed rapidly progressive crescentic glomerulonephritis and required treatment with cyclophosphamide and high-dose prednisone. Subsequently, renal function stabilized and RA remitted. Through the literature search and by reviewing information submitted to Cypress Biosciences Inc (manufacturer of Prosorba columns), available world literature on vasculitis secondary to Prosorba column treatment was compiled., Results: Immune complex deposition of staphylococcal Protein A (SPA)/SPA antibodies in the glomeruli precipitated the renal disease in our patient. Twenty cases of vasculitis (calculated prevalence, 1 per 400), 5 with internal organ involvement, have been reported in patients treated with Prosorba column for thrombocytopenic purpura. Seven RA patients treated with Prosorba column developed vasculitis (prevalence, 7 per 400), 3 with internal organ involvement., Conclusions: Vasculitis secondary to staphylococcal Protein A immunoadsorption therapy occurs rarely and appears to be related to development of SPA/SPA antibody immune complexes. Rheumatologists should be aware of this potentially serious complication of the Prosorba column treatment for RA., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Background: Reduction of pathological autoantibodies and circulating immune complexes can be useful in the treatment of autoimmune disease. Plasmapheresis has been shown to reduce autoantibody levels in systemic lupus erythematosus (SLE), but its effect on patients' outcome was not better compared with conventional immunosuppression in the past., Aim of the Study: Immunoadsorption as a selective extracorporeal immunoglobulin elimination technique was evaluated as rescue therapy in patients suffering from SLE., Methods: Eight patients with severe, therapy-resistant SLE underwent immunoadsorption onto protein A sepharose without concomitant immunosuppressants., Results: Remission of the disease was achieved in seven patients. Therapy had to be stopped in one patient because of side-effects. The best results were obtained when immunoadsorption was carried out daily, without supplementary intravenous immunoglobulin therapy. Oral cyclophosphamide for 3-6 months during follow-up was used to suppress relapse. Autoantibodies and circulating immune complexes were effectively eliminated regardless of their IgG subclass., Conclusion: Immunoadsorption onto protein A might be used as an extracorporeal treatment option in SLE when other therapies are ineffective.

Immunoadsorption therapy (IAT) is used in the treatment of autoimmune diseases. Although IAT has been reported to modify humoral immunity by inducing chemokines and activating complements, much remains unknown about the biological effects of IAT on cellular components in peripheral blood. To define the influence of IAT on leukocytes, we determined leukocyte L-selectin (CD62L) and Mac-1 (CD11b) as parameters for activation of leukocytes in peripheral blood during IAT. Peripheral leukocyte L-selectin and Mac-1 were determined continuously by flow cytometry in 6 patients with neuroimmunological disorders in whom IAT was conducted using a Plasma Flow OP-05 (Asahi Medical Corp., Tokyo, Japan) as a plasma separator and Immusorba TR-350 (Asahi Medical Corp., Tokyo, Japan) as an adsorption column. Expression of neutrophils (PMN) L-selectin was decreased 30 min after starting IAT, with the decreases particularly marked at the end of IAT, while expression of mononuclear cells (MNC) L-selectin slightly increased during IAT. Expression of PMN Mac-1 was markedly increased at the end of IAT, whereas expression of MNC Mac-1 did not change during IAT. Leukocyte counts decreased 30 min after starting IAT, and then increased to the initial level or higher in parallel with L-selectin downregulation and Mac-1 upregulation on PMN. L-selectin downregulation and Mac-1 upregulation on PMN suggested that activation of PMN associated with changes in peripheral leukocyte counts occurred during IAT and might play some role in modulating the human circulating blood and immune systems.

A patient with refractory idiopathic thrombocytopenic purpura developed widespread palpable purpura, fever, diarrhea, and arthralgias forty-eight hours following a third protein A immunoadsorption treatment. A skin biopsy revealed leukocytoclastic vasculitis. His skin lesions and constitutional symptoms resolved with administration of antibiotics and bed rest.

Background: The role of plasma exchange is well established in the management of myasthenia gravis, an autoimmune disorder characterized by muscle weakness and caused by circulating IgG antibodies with specificity against the acetylcholine receptor. Plasma antibody removal by conventional means, however, is nonselective and uses replacement fluids (chiefly, albumin solution) derived from human plasma., Study Design and Methods: The Canadian Apheresis Group undertook a study at two Canadian apheresis centers to clinically evaluate a staphylococcal protein A immunoadsorption system (EXCORIM) in myasthenia gravis patients., Results: The immunoadsorption system was safe and well tolerated. Ten of 12 patients had improvement in their neurologic status, as measured by a 20-point scoring system. The mean improvement in the weakness score was significant for the group (p = 0.0013)., Conclusion: Patients with myasthenia gravis respond to treatment with plasma immunoadsorption. Further studies are required for a cost-benefit analysis.

A 51-year-old woman was admitted to our hospital complaining of fever and general fatigue. Physical examination revealed butterfly-like erythema in face, facial edema and diffuse purpura all over her body. Laboratory data showed renal dysfunction, nephrotic syndrome and active phase of SLE. She was administered first methylprednisolone (1g/day/3 days by intravenous drip) then prednisolone (60 mg/day/month, orally) and had immune adsorption therapy for eight times. However, 14 days after the last session of immune adsorption, she developed fever of 39 degrees C and mild headache, and then 3 days later, she gradually became unconscious. Brain CT showed hydrocephalus. We diagnosed her as having tuberculous meningitis based on the detection of acid-fast bacillus in cerebrospinal fluid, and began treatment with antituberculous agents. We suspected that tuberculous meningitis had caused hydrocephalus. We tried percutaneous drainage of the left ventricle for hydrocephalus. Brain MRI showed a tuberculoma depicted as a mass of low intensity in the right cerebellum on the T1-weighted image, and of high intensity on the T2-weighted image, and the meninx in the basal cistern was enhanced. After treatment with antituberculous agents, we performed serial brain MRI and examined cerebrospinal adenosine deaminase activity (ADA). Despite treatment with antituberculous agents, new intracerebral tuberculomas had developed in some areas, whereas they had disappeared in other areas. After treatment for 4 months, the level of cerebrospinal ADA became normal, and the patient recovered consciousness despite the presence of multiple tuberculomas. Both the cell counts and the level of ADA in cerebrospinal fluid are the good indicators of the activity of tuberculous meningitis and reflected its clinical course. Furthermore, the level of ADA in cerebrospinal fluid changed with brain MRI image. Serial brain MRI and examination of ADA in cerebrospinal fluid were useful to know the activity of tuberculous meningitis and to evaluate the response to treatment.

Tryptophan column immunoabsorption therapy is beneficial to the patient with a neuroimmunological disease, but some complications have been attributed to this treatment. There have been some instances of an abrupt shock state along with severe decreases in blood pressure. In regards to this shock state, it has been reported that plasma bradykinin levels increase during tryptophan column immunoabsorption therapy. In this study, we examined the correlation between plasma bradykinin levels and either blood pressure or the levels of its degrading enzymes, angiotensin converting enzyme (ACE) and carboxypeptidase R (CPR) in 6 patients. Increased concentrations of bradykinin were present in the latter half of the therapeutic interval, and plasma bradykinin levels were found to be inversely correlated to CPR activity. The decreased CPR level could augment the activities of bradykinin. We speculate that bradykinin could be responsible for the hypotension occurring in patients during tryptophan column immunoabsorption therapy and that the metabolism of bradykinin could be caused by the decreased activity of CPR.

Immunoadsorption plasmapheresis (IAP) using a tryptophan linked gel column has been shown to effectively remove serum IgG anti-GQ1b antibody which may contribute to the pathogenesis of Miller Fisher syndrome. Two patients are reported on with Miller Fisher syndrome, who developed bilateral facial palsy during IAP using a tryptophan column, while ophthalmoplegia, ataxia, and, areflexia were improving. In these patients, the titre of anti-GQ1b antibodies was reduced. The IAP using a tryptophan column has a beneficial effect on Miller Fisher syndrome but may not inhibit the development of facial palsy. The mechanism of such a dissociated effect of IAP on Miller Fisher syndrome is discussed.