Immunoadsorption or plasma exchange in steroid-refractory multiple sclerosis and neuromyelitis optica.

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.

Treatment of Autoimmune Bullous Disorders in Pregnancy.

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.

Comparing the efficacy of three techniques to reduce isoagglutinin titers in AB0 incompatible kidney transplant recipients.

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.

Immunoadsorption for autoimmune encephalitis.

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.

Immunoadsorption for treatment of severe atopic dermatitis.

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.

Successful and well-tolerated bi-weekly immunoadsorption regimen in pemphigus vulgaris.

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.

Low rate of infectious complications following immunoadsorption therapy without regular substitution of intravenous immunoglobulins.

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.

A prospective study comparing tryptophan immunoadsorption with therapeutic plasma exchange for the treatment of chronic inflammatory demyelinating polyneuropathy.

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.

Extracorporeal IgE Immunoadsorption in Allergic Asthma: Safety and Efficacy.

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.

Protein a Immunoadsorption May Hamper the Decision to Transplant Due to Interference With CDC Crossmatch Results.

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.

Clinical outcomes with ABO antibody titer variability in a multicenter study of ABO-incompatible kidney transplantation in the United Kingdom.

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.

Effect of combined treatment with immunoadsorption and membrane filtration on plasma coagulation--Results of a randomized controlled crossover study.

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.

Targeting IgE in Severe Atopic Dermatitis with a Combination of Immunoadsorption and Omalizumab.

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.

Adverse events of lipoprotein apheresis and immunoadsorption at the Apheresis Center at the University Hospital Dresden.

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.

Treatment of minor severe acquired haemophilia. Is there a rationale for immunoadsorption?

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.

Effects of different lipoprotein apheresis methods on serum protein levels.

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.

Immunoadsorption with regenerating systems in neurological disorders --A single center experience.

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.

Immunoadsorption can improve cardiac function in transplant candidates with non-ischemic dilated cardiomyopathy associated with diabetes mellitus.

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 ß1-autoantibodies (ß1-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 ß1-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 ß1-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.

Apheresis in treatment of acute inflammatory demyelinating disorders.

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.

Fibrinogen reduction and bleeding complications in plasma exchange, immunoadsorption and a combination of the two.

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.