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Introduction Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a rare and life-threatening autoimmune disease. Immunoadsorption (IA) is a potential approach in treating AAV. Patients and methods A 76-year-old male patient was admitted with hemoptysis and oliguria, progressed rapidly into pulmonary hemorrhaging, acute kidney damage, and multi-organ failure. He was diagnosed as MPO-ANCA-positive vasculitis by immunological detection and kidney biopsy in the case report. IA combined with methylprednisolone to induce and alleviate the disease effectively, and cyclophosphamide (0.2 g every other day, a total of 1 g for the first time, after the patients tolerated, 10 mg/kg every 3 weeks for 6 months in total) combined with prednisone for maintenance therapy. Results and discussion Although both kidneys suffered severe deterioration requiring long-term hemodialysis replacement therapy, their pulmonary function was restored. Furthermore, clinical and serological symptoms of the disease were successfully controlled. Consequently, IA treatment may quickly remove IgG and ANCA to efficiently control clinical symptoms, especially in patients presenting with alveolar hemorrhaging and acute renal failure.

International audience; Primary focal and segmental glomerulosclerosis (FSGS) frequently recurs after transplantation and is associated with a poor prognosis. We describe here the successful kidney graft reuse in an adult recipient, 8 months after early primary FSGS recurrence resistant to all available therapeutics. Patient 1, a 23-year-old man, followed for kidney failure secondary to primary FSGS, was first transplanted in 2018 with a deceased donor graft. Unfortunately, we observed an immediate recurrence of biopsy-proven primary FSGS. After 4 lines of treatment (intravenous cyclosporine + corticosteroids, plasma exchanges, immunoadsorption, and rituximab), the patient was still highly nephrotic and kidney function was slowly deteriorating. After approval from both the patient and the health authority (Biomedicine Agency), the graft was detransplanted 8 months after transplantation and reimplanted in patient 2, a 78-year-old nonimmunized and anephric recipient (bi-nephrectomy 2 years previously for bilateral renal carcinoma). We observed immediate kidney function and progressive resolution of proteinuria (serum creatinine of 1.2 mg/dL and proteinuria of 0.1 g/d 1 year later). Biopsies performed after surgery showed persistent FSGS lesions with a decrease in overall foot-process effacement. To our knowledge, this is the first reported case showing that kidney graft transfer may still be a viable option for refractory primary FSGS several months after transplantation.

Idiopathic nephrotic syndrome (INS) is characterized by three different entities, namely minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS) and membranous nephropathy (MN). While there is an increasing understanding of primary MN with the discovery of antibodies directed against phospholipase A2 receptor (PLA2R Ab) and thrombospondin type 1 domain-containing 7A, circulatory factors causative of inducing MCD and FSGS remain in part elusive. Extracorporeal treatment forms (mostly plasma exchange) have been reserved for patients with either a disease course refractory to commonly prescribed immunosuppressive drugs or to patients with recurrence after kidney transplantation. There is a paucity of data supporting the use of immunoadsorption (IAS) in the management of MCD and MN and evidence to perform LDL-apheresis in the former is limited to reports from Japan. Treatment with IAS in primary FSGS has shown mixed responses, possibly biased by including treatment-resistant cases in the absence of genetic testing. In those with recurrence of the disease following kidney transplantation, IAS has shown high remission rates with an acceptable safety profile. There is a need to compare IAS to plasma exchange (PLEX) in this indication and due to a higher amount of plasma processed during one session, IAS may have advantages over PLEX. Removal of PLA2R Ab by IAS is currently being tested in a phase II clinical trial. More clinical trials in a prospective and randomized fashion need to be designed to prove the concept that IAS may be a treatment option for INS. While PLEX is still the leading extracorporeal treatment form in these indications, this review aims to highlight the efficacy and safety of IAS in the management of INS.

Since the discovery of carbohydrate nature of the antigens related to ABO blood group system in the middle of 20th century, an interest to synthetic approaches to these oligosaccharides is very high. ABH glycans are required for clinical applications, namely, immunoadsorption and blood typing, as well as for scientific investigations in the areas of hematology, immunology and glycobiology. In this article, the chemical syntheses of various ABH glycans and related structures are reviewed, and examples of their use for clinical purposes are collected.

Summary: Background: Plasma exchange (PE) constitutes the standard therapy for steroid-refractory relapse in multiple sclerosis and clinically isolated syndrome. Immunoadsorption (IA) is an alternative method of apheresis which selectively removes immunoglobulines (Ig) while preserving other plasma proteins. Although IA is regarded as a well-tolerated, low-risk procedure, high-level evidence for its efficacy is lacking. Therefore, we sought to investigate whether IA is superior to PE in patients with acute relapse of multiple sclerosis or clinically isolated syndrome who had insufficiently responded to high-dose intravenous methylprednisolone (MP). Methods: Patients with acute relapse of multiple sclerosis or clinically isolated syndrome and without complete clinical remission of symptoms after at least one cycle of high-dose intravenous MP therapy were enrolled to our randomised, controlled, parallel-group, monocentric trial. Eligible patients were aged at least 12 years and had no clinical or laboratory signs of systemic infection. Eligible patients were randomly assigned (1:1) to receive either IA or PE. Patients in both groups received 5 treatments on 5 consecutive days. In the IA group, the 2.0-fold individual total plasma volume was processed on day 1, and the 2.5-fold on days 2–5. In the PE group, 2 liters of plasma (corresponding to the 0.69 ± 0.12-fold individual total plasma volume) were removed each day and substituted by 5% human albumin solution. Patients were followed up directly after last apheresis as well as 2 and 4 weeks after last treatment. The primary endpoint was change of the Multiple Sclerosis Functional Composite (MSFC) after 4 weeks compared to baseline. Analyses of primary outcome and safety measures were done in all patients who received at least one treatment (intention-to-treat-population). The trial is registered with ClinicalTrials.gov, number NCT02671682. Findings: Between January 21, 2016, and October 26, 2018, 63 patients were screened for eligibility, and 61 patients were randomly assigned to receive IA (n = 31) or PE (n = 30). All randomised patients were included in the intention-to-treat-analysis. For the primary outcome, the median improvement of MSFC after 4 weeks compared to baseline was 0.385 (IQR 0.200–0.675; p

Introduction Therapeutic apheresis (TA) represents a treatment option for pre-existing conditions or diseases occurring during gestation. Although pregnancy is not a contraindication per se, due to the lack of evidence-based guidelines and presumed risk of maternal/fetal adverse events there is a general resistance to its application. Material and methods Between January 2005 and August 2017, at the Apheresis Unit of the University Hospital of Padua 936 TA procedures were performed during 57 pregnancies in 48 patients: 813 Plasma Exchange sessions, 119 Immunoadsorptions, 4 Red Blood Cell exchanges. The treated disease were as follows: antiphospholipid syndrome (18 patients), autoimmune congenital heart block (18), myasthenia gravis (3), Rh alloimmunization (2), systemic sclerosis (1), suspected autoimmune encephalitis (1), severe hypertriglyceridaemia (1), post partum hemolytic-uremic syndrome (1), sickle cell disease (1), lupus nephritis (1) and thrombotic thrombocytopenic purpura (1). Results In the time period considered the apheresis sessions applied to pregnant women were 7.1% of the total (n = 13.251). The median age at the first treatment was 33 years. The median week of gestation (WG) at the beginning of treatments was 21. Twenty (2.1%) sessions were complicated by adverse events, none requiring or prolonging hospitalization. There were 50 live births, 5 spontaneous abortions and 2 voluntary terminations of pregnancy. Median WG at delivery was 35 and caesarean section was performed in 46 cases. Conclusions Our data showed that TA in pregnancy is well tolerated. Close collaboration between clinician, obstetrician and TA specialist is crucial to ensure a good outcome of high-risk pregnancies.

Pemphigoid is the most common autoimmune blistering disease. IgG and IgE autoantibodies against the hemidesmosomal antigens Bullous Pemphigoid (BP) 180 and BP230 are of pathogenic relevance, since autoantibody-antigen binding results in complement activation, immune cells infiltration, impaired hemidesmosomal function, and loss of dermal-epidermal adhesion. Systemic steroids and immunosuppressants are frontline therapies in pemphigoid, but result in substantial morbidity and increased mortality. A large randomized multicenter study highlighted doxycycline as a feasible alternative to systemic corticosteroids in patients not suitable for long-term steroid use. In recent years, new targeted therapies, including intravenous immunoglobulin (IvIg), rituximab, omalizumab, and immunoadsorption, have proven efficacy in the refractory setting, but, with the exception of IVIG, large randomized trial has not been performed yet. Basic research studies have now shed light on the pathogenic role of eosinophils and autoreactive T-helper 2 cells in pemphigoid, inducing tissue damage and sustaining autoantibody production by autoreactive B-cells, respectively. Indeed, eosinophils and Th2-related cytokines have become attractive therapeutic options. Moreover, Interleukin-17 related inflammatory pathways have been also shown to participate in the blistering process. This review discusses current evidence for the use of targeted therapies in pemphigoid as well as most relevant pharmacologic advances and new drugs currently under clinical investigation.

Background Since 1996, ABO-incompatible heart transplantation has been undertaken by performing whole-body plasma exchange to remove isohemagglutinins using the cardiopulmonary bypass (CPB) circuit at the time of transplantation. This requires large volumes of donated blood and blood products, causes hemodynamic instability during the exchange transfusion, and limits practical use to small children. We sought to determine the efficacy of anti-A/B immunoadsorption within the CPB circuit on removal of isohemagglutinins in an ex vivo setting before its use clinically. Methods An anti-A/B immunoadsorption column was placed into a CPB circuit mimicking a typical ABO-incompatible transplant patient, which had been primed with type O whole human blood. Samples were taken for determination of isohemagglutinin titers following each plasma volume pass through the anti-A/B immunoadsorption column. Results There was a linear decrease of at least 1 dilution seen in both anti-A and anti-B IgG and IgM antibodies with each plasma volume pass through the column. This predictable removal allowed the formulation of selection criteria for ABO-incompatible heart transplantation given the reciprocal of titer and patient weight. This degree of predictability allowed us to use it successfully in the clinical setting, reducing antibodies to an undetectable level during ABO-incompatible heart transplantation. Conclusions The incorporation of an anti-A/B immunoadsorption column into the extracorporeal circuit reduces allogeneic blood product requirement for ABO-incompatible heart transplantation, while providing efficacious removal of anti-A and anti-B isohemagglutinins. This can be undertaken within the time period of CPB before graft reperfusion and expands the potential recipient pool to larger patients with higher isohemagglutinin titers.

Apheresis has been used in the treatment of severe systemic vasculitides, in conjunction with immunosuppressive therapies, for over 40 years. The aim is to rapidly remove autoantibodies or circulating immune complexes from the plasma. The two main indications at present are vasculitis associated with Antineutrophil Cytoplasmic Antibodies (ANCAs) manifesting as severe renal involvement and/or intraalveolar hemorrhage and antiglomerular basement membrane disease (Goodpasture syndrome). The ongoing PEXIVAS randomized controlled trial is assessing plasmapheresis to treat ANCA-associated vasculitis with or without severe renal involvement or intraalveolar hemorrhage. The two main apheresis techniques used to treat systemic vasculitis are plasmapheresis (by filtration, centrifugation, or double filtration) and immunoadsorption. The advantages and drawbacks of each technique are discussed here. Whether one technique is superior over the other in the current indications has not been proven.

Introduction Data suggest an additional role of T cells in antibody-mediated rejections. In 2001 a protocol for AB0-incompatible kidney transplantation based on B-cell–depleting anti–CD20 antibody rituximab, antigen-specific blood group IgG immunoadsorption, intravenous immunoglobulins, and triple immunosuppression was introduced in Europe, which used induction therapy with the use of interleukin-2 receptor antibody (IL2-RA) basiliximab. We used thymoglobulin in AB0-incompatible patients as induction in the face of high immunologic risk. Methods We retrospectively evaluated a cohort of 9 AB0i living donation (LD) recipients from 2011 to 2014. Desensitization included blood group–specific immunoadsorption. Eighteen AB0-compatible LD recipients receiving induction therapy with thymoglobulin served as control subjects. Another control group consisted of 18 AB0-compatible LD recipients receiving basiliximab. Follow-up was 24 months. We captured graft function by estimating glomerular filtration rate (eGFR by Modification of Diet in Renal Disease formula), rejection episodes, and bacterial and viral infections. Results All patients experienced immediate graft function. No significant or clinical differences were observed regarding graft function, rejection rates, or infections between the groups, although there seemed to be slightly higher cytomegalovirus infection rates due to preemptive therapy strategy. Conclusions Thymoglobulin appears to be similar in safety and efficacy to IL-2-antagonists in AB0i kidney transplantation.

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.

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.

We aimed to evaluate the value of immunoadsorption (IA) treatment after the failure of intravenous methylprednisolone (IVMP) therapy for neuromyelitis optica spectrum disorder (NMOSD). Sixty-one NMOSD attacks unresponsive to IVMP were included: 22 patients received rescue IA (IVMP+IA), 24 underwent rescue plasma exchange (PE) (IVMP+PE), and 21 received no further rescue therapy (IVMP alone). The improvement frequencies were higher in the IVMP+IA and IVMP+PE groups than in the IVMP-alone group (P = 0.024). The effective period for IA treatment may be longer than previously thought. IA treatment for IVMP-resistant NMOSD attacks was effective and comparable to PE treatment.

Antiglomerular basement membrane glomerulonephritis is a rare autoimmune disease characterized by rapidly progressive glomerulonephritis that may be associated with pulmonary hemorrhage (Goodpasture syndrome). The disease is caused by autoantibodies (classically IgGs) directed against the α3 subunit of type IV collagen. This is a rare disease in the adult population and extremely rare in children, with a reported cumulative annual incidence at 1/106 people/year. Among scarce reported pediatric cases (n=31), most are girls (M/F sex ratio, 1:4), and the mean age at diagnoses is 9.2±4.6 years. A medical diagnosis is an emergency and is based on the identification of specific antibodies in the serum, and pathognomonic linear fixation of IgGs along the glomerular basement membrane. Without appropriate treatment, the disease is generally fulminant, and patient and kidney survival is poor. Indeed, glomerular function strongly correlates with histological lesions. The current guidelines recommend the use of plasma exchanges and immunosuppressive drugs. For the past few years, alternative therapeutics such as specific anti-B-cell antibodies (rituximab) or specific extrarenal cleansing such as immunoadsorption have been successfully used in adults. Immunoadsorptions (IAs) can remove pathogenic IgGs from the circulation and do not require plasma infusions, contrary to plasma exchanges. In this review, we discuss the key points of antiglomerular basement membrane glomerulonephritis diagnosis and conventional or alternative therapeutics.

Immusorba TR (IM-TR) and PH (IM-PH) were developed as immunoadsorbents from nonbiological materials as affinity ligands for removal of pathogenic substances. The immunoadsorbents in IM-TR and IM-PH are immobilized on a polyvinyl alcohol gel with tryptophan and phenylalanine, respectively, as a ligand. IM-TR is mainly clinically applied to autoimmune neurological diseases such as myasthenia gravis, Guillain-Barré syndrome, and multiple sclerosis. IM-PH is also applied to neurological diseases but mainly to rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. Many autoantibodies with different specificities have been found to have similar affinity for the ligand of Immusorba, and it is expected that Immusorba will be used against more diseases and help to elucidate the pathogenesis of diseases via identification of unknown pathogenic substances adsorbed to Immusorba.

Summary Autoantibodies play an important role in the pathophysiology of renal involvement in systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), systemic vasculitis, and anti–glomerular basement membrane disease (or Goodpasture syndrome). Direct removal of autoantibodies therefore has been tried in various ways, first by plasma exchange. Today, immunoadsorption is the extracorporeal method that most effectively removes (pathogenic) immune complexes and antibodies. Although past data have shown efficacy and biocompatibility of immunoadsorption in (renal) SLE, it is still an experimental and expensive procedure, and evidence from randomized controlled trials is needed. Nevertheless, immunoadsorption is being used as a rescue therapy in life-threatening situations of SLE patients because of its fast mode of action and its acceptable safety profile. In granulomatosis with polyangiitis (GPA) (or Wegener’s granulomatosis), microscopic polyangiitis (MPA), and anti–glomerular basement membrane disease, the current standard is plasma exchange. Immunoadsorption, which probably would reduce the autoantibody burden more effectively, might be an even better more effective option, but sufficient evidence is lacking.

Background Among various cardiac autoantibodies (AAbs), those recognizing the β 1 -adrenergic receptor (β 1 AR) demonstrate agonist-like effects and induce myocardial damage that can be reversed by β-blockers and immunoglobulin G3 (IgG3) immunoadsorption. Objectives The goal of this study was to investigate the role of β 1 AR-AAbs belonging to the IgG3 subclass in patients with recent-onset cardiomyopathy. Methods Peripheral blood samples were drawn at enrollment in patients with recent-onset cardiomyopathy (left ventricular ejection fraction [LVEF] ≤0.40; 1 AR-AAb was determined, and echocardiograms were assessed, at baseline and 6 months. Patients were followed up for ≤48 months. Results Among the 353 patients who had blood samples adequate for the analysis, 62 (18%) were positive for IgG3-β 1 AR-AAbs (IgG3 group), 58 (16%) were positive for IgG but not IgG3 (non-IgG3 group), and the remaining were negative. There were no significant differences in baseline systolic blood pressure, heart rate, or LVEF among the groups at baseline. Left ventricular end-diastolic and end-systolic diameters were significantly larger in the non-IgG3 group compared with the other groups (left ventricular end-diastolic diameter, p 1 AR-AAb was an independent predictor of LVEF at 6 months and change in LVEF over 6 months, even after multivariable adjustment (LVEF at 6 months, β = 0.20, p = 0.01; change in LVEF, β = 0.20, p = 0.008). In patients with high New York Heart Association functional class (III or IV) at baseline, the IgG3 group had a lower incidence of the composite endpoint of all-cause death, cardiac transplantation, and hospitalization due to heart failure, whereas the non-IgG3 group had the highest incidence of the composite endpoint. Conclusions IgG3-β 1 AR-AAbs were associated with more favorable myocardial recovery in patients with recent-onset cardiomyopathy.

Background Elimination of cardiac autoantibodies, frequently detected in patients with dilated cardiomyopathy (DCM), with immunoadsorption (IA) improves functional capacity and left ventricular (LV) function. This study aimed to prospectively address this issue in a large cohort of unselected patients. Methods Consecutive patients undergoing IA followed by IgG substitution were included. Clinical and echocardiographic parameters were assessed at baseline (BL) and 12-month follow-up (FU). Patients were classified as IA responders when ≥2 of the following criteria were achieved: improvement in the Minnesota Living with Heart Failure Questionnaire (MLHFQ) ≥5 points, symptoms [≥1 New York Heart Association (NYHA) class], LV ejection fraction (EF) ≥10% or decrease in LV end-diastolic diameter (EDD) ≥10%, or N-terminal pro B-type natriuretic peptide (NT-pro-BNP) ≥50%. Results 93 patients (median age 61 years, LVEF 30%, duration of symptoms 14 months, 87% in NYHA class III/IV, >90% treated with β-blocker/angiotensin-converting enzyme inhibitor) were included. When the entire cohort was analyzed, a significant improvement in MLHFQ (50 vs. 26 points), NYHA-class (median 3.0 vs. 2.0), LVEF (30% vs. 38%), LVEDD (62 vs. 59 mm), NT-pro-BNP (892 vs. 523 pg/ml) was observed at FU ( p n = 43) were classified as responders. Those were characterized by a shorter disease duration (11 vs. 22 months), larger BL LVEDD (64 vs. 60 mm), presence of >1 viral genome, and higher values of mononuclear inflammatory cells at endomyocardial biopsy. Sixteen (17.2%) patients experienced IA related complications. Conclusions A positive response is observed in 48% of inflammatory DCM patients undergoing IA, and this translates into a significant improvement in clinical and echocardiographic parameters.

Purpose The diagnosis and treatment of antibody-mediated rejection (AMR) after LTx has gained increasing recognition within the transplant community. Extracorporeal photopheresis (ECP) modulates various pathways of the immune system and is currently used to treat CLAD. In AMR, adding ECP to established AMR treatments could potentially prevent rebound of DSA. This study aimed to analyze the role of ECP as adjunct treatment of AMR. Methods Patients who developed antibody-mediated rejection between 2009 and 2019 were included in this single-center retrospective analysis. The following parameters were evaluated: DSAs, C4d deposition and lung histology. Results A total of 39 patients developed clinical AMR during follow-up. Nineteen (48%) patients had positive DSA against HLA Class I and eighteen (46%) HLA Class II. Median time to diagnosis of AMR was 180 days (IQR: 2-2477). First line treatment was immunoadsorption (IA) in 34 (87%) patients, intravenous immunoglobulins with concomitant immunoadsorption in 3 (8%) patients and in 2 cases ATG. Twenty (51%) patients primarily treated with IA and the two patients treated with ATG received ECP. Among the patients treated with ECP, 12 had DSA against HLA Class I and 13 against HLA Class II. ECP treatment was initially performed twice a week. After stabilization of lung function and improvement of clinical situation, ECP was then performed once a month for a minimum of 6 months. Median length of treatment was 12 months. Patients who received ECP after first line treatment had 1-year survival rate of 62% compared to 27% of other AMR patients. In all patients treated with IA followed by ECP, DSA disappeared or MFI reduced below our institutional threshold of 5000. Conclusion Extracorporeal photopheresis is associated with a reduction of de novo DSA after antibody-mediated rejection. Prospective studies are necessary to confirm the beneficial effect of ECP as an add-on therapy after AMR.

Purpose Antibody mediated rejection (AMR) has recently emerged as an important risk factor for lung allograft dysfunction and mortality. Several clinical protocols have been proposed to try to remove donor specific antibodies (DSA) and prevent their future development, including intravenous immunoglobulin (IVIG), therapeutic plasma exchange (TPE), rituximab and other. Unlike traditional TPE, immunoadsorption (IAS) is a blood-purification technique that enables the selective removal of immunoglobulins from separated plasma through high-affinity adsorbers; advantageously, IAS does not remove other plasma components such as fibrinogen and compounds of the coagulation cascade, reducing potential adverse effects. Our centre implemented a multimodality strategy including steroids, immunoadsorbption, IVIG and Rituximab. Methods All adult lung transplant (LuTx) recipients receiving a diagnosis of AMR (based on 2016 ISHLT consensus definition), were considered eligible to receive this treatment: pulsed methylprednisolone (10 mg/Kg), 5 cycles of IAS, IVIG (2 g/Kg) and rituximab (375 mg/m^2). Of note, C4d staining is not currently available at our institution. Results Between 2016 and 2018, four patients received multimodality antibody directed therapy for AMR after LuTx. Details can be found in table 1. 2 out of the 4 patients qualified for chronic lung allograft dysfunction (CLAD) prior to protocol start (patient 1 and 3). No adverse events were registered during IAS procedures, but patient 3 suffered transfusion related acute lung injury while receiving IVIG. However, patient 3′s death was attributed to progressive allograft failure and not to the therapy itself. Conclusion Following this treatment, while the total number of the original DSA and the value of MFI of the originally observed DSA decreased, clinical outcomes were variable: 2 patients are experiencing long term clinical stability, but the others rapidly progressed to severe CLAD.

To determine the efficacy of immunotherapy in limbic encephalitis (LE) associated epilepsies with autoantibodies against intracellular antigens in the forms of paraneoplastic autoantibodies versus glutamic acid decarboxylase 65 (GAD)-autoantibodies.Eleven paraneoplastic-antibodies+ and eleven age- and gender-matched GAD-antibodies+ patients with LE were compared regarding EEG, seizure frequency, MRI volumetry of the brain, and cognition. All patients received immunotherapy with corticosteroids add-on to antiepileptic therapy. A few patients underwent additional interventions like immunoglobulins or immunoadsorption.Immunotherapy led to a significantly greater proportion of seizure-free patients in the paraneoplastic antibodies+(55%) as compared to GAD-antibodies+(18%) patients (p0.05). Impaired cognition was evident initially (total cognitive performance score based on attentional-executive function, figural/verbal memory and word fluency) in 100% of the paraneoplastic-antibodies+ and 73% of the GAD-antibodies+ group. After therapy, cognition improved significantly in the paraneoplastic-antibodies+, but not in the GAD-antibodies+ patients (p0.05). Cognitive change did not correlate with the change in the number of antiepileptic drugs over time. MRI showed larger and unchanged volumes of the amygdala, presubiculum and subiculum in GAD-antibodies+as compared to paraneoplastic-antibodies+patients (p0.05) over time.Our data provide evidence of a beneficial effect of immunotherapy added to antiepileptic drugs on seizure frequency and cognition only in the paraneoplastic-antibodies+ subgroup of LE presenting autoantibodies against intracellular antigens.

Background Liver transplantation is one of the solid organs most commonly being transplanted across the world. The indications, affordability and accessibility have grown manifold. To increase the donor pool, inclusion of ABO incompatible liver donors is being considered. To enhance the graft functioning and survival, immunoadsorption apheresis to reduce the ABO hemagglutination titres are on the rise. Case Report We report three cases ABO incompatible liver transplantation with immunoadsorption protocol. The patients were in poor general condition with Child-Turcotte-Pugh (CTP) class ‘C’ and there were no suitable ABO compatible grafts at the time. For all three cases, immunosuppressive protocol consisted of induction with Rituximab, followed by tacrolimus, mycophenolate mofetil and corticosteroids. The third patient received basiliximab for induction, in addition to the above protocol. First 2 patients received 1 immunoadsorption (IA) session with Glycosorb ABO® system (Glycorex AB, Sweden), pre-operatively. The third patient received 2 IA sessions pre-operatively. Baseline IgM plus IgG titres were 1024; 64 and 1024 for anti-B, anti-A and anti-B for patient 1, 2 and 3 respectively. Target pre-operative antibody titre was ≤16. Average post-operative length of stay was 17.3 days. There were no acute rejection. None of them, required any post-operative plasma exchange. Conclusion Immunoadsorption is effective in reducing hemagglutination titres in recipients of ABO incompatible donor liver.

Refractory lupus nephritis indicates an inadequate response to lupus nephritis therapy. It implies persisting or worsening disease activity despite therapy, but the definition is complicated by the parameters of response, proteinuria and renal function, that do not discriminate clearly between activity and irreversible damage. Understanding the causes of refractory disease and developing treatment strategies is important because these patients are more likely to develop poor outcomes, especially end stage renal disease. This review explores current concepts and definitions of refractory disease and summarises treatment approaches that have been used in observational cohort studies and case series. We highlight the importance of optimising adherence to the prescribed immunosuppressive and supportive measures and avoidance of diagnostic delay. Treatment options include higher dose glucocorticoid, switching between cyclophosphamide and mycophenolate acid derivates, or addition of rituximab, the latter potentially in combination with belimumab. Less evidence supports extracorporeal treatment (plasma exchange or immunoadsorption), calcineurin inhibitors (cyclosporine A or tacrolimus), intravenous immunoglobulin and stem cell transplantation. Improvements in understanding what refractory disease is and how definitions can be integrated into treatment pathways has the potential to enhance lupus nephritis outcomes.

Anti-aquaporin-4 (AQP4) antibody-positive optic neuritis is a condition in which a patient testing positive for anti-AQP4 antibody presents with optic neuritis only. The disease is classified as a neuromyelitis optica spectrum disorder (NMOSD) and is a steroid-resistant refractory optic neuritis. Patients are treated by oral administration of steroids, steroid pulse therapy, and apheresis therapy. The patient in our case was a 48-year-old female who was diagnosed with anti-AQP4 antibody-positive optic neuritis by her ophthalmologist, and was referred to our hospital. Selective plasma exchange (SePE) was initially started, but she strongly preferred treatment as an outpatient due to family circumstances. Therefore, selective immunoadsorption (SeIA) was used from the second session to minimize loss of coagulation factors. The RRs were 16.5-33.3% for anti-AQP4 antibody, 7.48-18.57% for fibrinogen, and 0.8-4.57% for factor XIII. After the 7th SeIA session, the patient was followed up with a maintenance dose of 10 mg/day oral prednisolone as an outpatient at our Department of Ophthalmology. This is the first report to investigate the removal rate (RR) of anti-AQ4 antibody using SeIA. In our case, the anti-AQP4 antibody level before the last SeIA session was still not completely negative, but there was clinical improvement in vision. SeIA was highly effective in maintaining coagulation factor levels. Therefore, our results suggest that SeIA is a safe treatment that can be performed in an outpatient setting.

An elevated plasma concentration of lipoprotein (a) [Lp(a)] is an independent risk factor for cardiovascular disease. Life style modification and currently available drugs either fail to effectively lower plasma Lp(a) levels or do not result in clinical benefit. However, lipoprotein apheresis is very efficient in decreasing Lp(a) concentrations. A single apheresis session can acutely decrease Lp(a) by approximately 60-75%, and apheresis performed weekly or biweekly results in considerably decreased mean interval concentrations (approximately 25-40% reduction). While most apheresis systems (heparin-induced extracorporeal LDL precipitation, direct adsorption of lipoproteins, lipoprotein apheresis with dextran-sulfate, lipid filtration, immunoadsorption) decrease LDL and Lp(a), Lipopac is specific and only decreases Lp(a). Lp(a) apheresis is expensive and time consuming, but associated with very few side effects. Two randomized controlled trials give conflicting consults with respect to the effect on angiographic changes. Retrospective analyses indicate that regular apheresis translates into clinical benefit in patients with elevated Lp(a), but adequate randomized controlled trials are lacking.

The goal of this project was to study the feasibility of using a DNA-immobilized nanocellulose-based immunoadsorbent for possible application in medical apheresis such as systemic lupus erythematosus (SLE) treatment. Calf thymus DNA was bound to high surface area nanocellulose membrane at varying concentrations using UV-irradiation. The DNA-immobilized samples were characterized with scanning electron microscopy, atomic force microscopy, and phosphorus elemental analysis. The anti-ds-DNA IgG binding was tested in vitro using ELISA. The produced sample showed high affinity in vitro to bind anti-ds-DNA-antibodies from mice, as much as 80% of added IgG was bound by the membrane. Furthermore, the binding efficiency was quantitatively dependent on the amount of immobilized DNA onto nanocellulose membrane. The described nanocellulose membranes are interesting immunoadsorbents for continued clinical studies.

Pregnant women with triple antibody positive antiphospholipid syndrome (APS) who have had thrombosis or a history of early, severe pregnancy complications are generally considered at high risk of pregnancy loss. The objectives of this study were to investigate the efficacy and safety of a relatively new treatment protocol used in addition to conventional therapy in high-risk pregnant patients affected with primary APS. The study's two inclusion criteria were: (1) the presence of triple antiphospholipid positivity, (2) previous thrombosis and/or a history of one or more early, severe pregnancy complications. Eighteen pregnancies occurring between 2002 and 2015 in 14 APS patients, (mean age 34.8±3.6 SD) were monitored. All 14 (100%) patients had triple antiphospholipid positivity. In addition, six of them (42.8%) had a history of thrombosis, four (28.6%) had one or more previous early and severe pregnancy complications, and four (30.8%) met both clinical study criteria. The study protocol included weekly plasmapheresis or immunoadsorption and fortnightly 1g/kg intravenous immunoglobulins. Seventeen of the pregnancies (94.4%) produced live neonates, all born between the 26th and 37th weeks of gestation (mean 33.1±3.5 SD). One female (5.5%), born prematurely at 24 weeks, died of sepsis a week after birth. There were two cases (11.1%) of severe pregnancy complications. No treatment side effects were registered. Given the high live birth rate and the safety associated to it, the study protocol described here could be taken into consideration by medical teams treating high-risk APS pregnant patients.

Cardiomyopathies such as idiopathic dilated cardiomyopathy (DCM), Chagas' cardiomyopathy and Peripartum cardiomyopathy present with autoantibodies against G-protein coupled receptors (GPCR-AABs) that agonistically activate their receptors. For the treatment of "agonistic autoantibody diseases" and in particular DCM, the removal of the GPCR-AABs by immunoadsorption (IA) has been studied with convincing patient benefit. To overcome cost and logistics problems of IA, the application of the aptamer BC007 for in vivo neutralization of GPCR-AABs could help. We demonstrate here, that the aptamer neutralized, in vitro, the presently known cardiovascular-pathogenic GPCR-AABs. In spontaneously hypertensive rats, the aptamer demonstrated its GPCR-AAB neutralizing potency in vivo. In the serum of DCM patients, the same GPCR-AAB reduction was achieved when patients were either immunoadsorbed or patient's serum was ex vivo treated with the aptamer. In our view, aptamer BC007 treatment in GPCR-AAB-positive patients would have a comparable benefit as that seen after IA. Not knowing all that interfering with our idea of aptamer-dependent neutralization of GPCR-AABs, the first preliminary steps have been taken for bringing the idea closer to patients.

This report describes how donor- and recipient-derived immunity was influenced by immunosuppressive treatment of ABO incompatibility (rituximab and immunoadsorption/plasmaphereses) in the long-term. We present an 8-year course of Hepatitis B virus (HBV) immunity, isohemagglutinins and B cell numbers. Whereas cellular HBV immunity was transferred from the HBV vaccinated donor (blood group A1) to the HBV naïve recipient (blood group 0), humoral HBV specific immune transfer was lacking. Starting at month 17 after transplantation, the recipient was vaccinated six times against HBV. Anti-HBs did not appear until the sixth vaccination at month 44. Immunoadsorption prior to transplantation reduced anti-A1 IgG titers from 256 to 2. Titers after transplantation remained low (⩽64). B cell numbers were below standard values up to month 26, then normalized and exceeded normal values from year 7 to 8 post transplantation. In conclusion, donor-derived B cell immunity was lost but recipient-derived immunity persisted after ABO incompatible transplantation.

ABO-incompatible kidney transplantation (ABOi KT) was introduced to expand the donor pool and minimize shortage of kidneys for transplantation. Because improved outcomes of ABOi KT were reported in Japan in the early 2000s, the number of ABOi KTs has been increasing worldwide. In addition, a better understanding of immune pathogenesis and subsequent aggressive immunosuppression has helped to make effective desensitization protocols. Current strategies of ABOi KT consist of pretransplant antibody removal using plasmapheresis or immunoadsorption to prevent hyperacute rejection and potent maintenance immunosuppression, such as tacrolimus and mycophenolate mofetil, to inhibit antibody-mediated rejection. Recent outcomes of ABOi KT are comparable with ABO-compatible KT. However, there are still many problems to be resolved. Very high anti-ABO antibody producers are difficult to desensitize. In addition, ABOi KT is associated with an increased risk of infection and possibly malignancy due to aggressive immunosuppression. Optimization of desensitization and patient-tailored immunosuppression protocols are needed to achieve better outcomes of ABOi KT. This review provides an overview of the history, immune mechanism, immunosuppressive protocol, outcomes, current obstacles, and future perspectives in ABOi KT.

ABO-incompatible (ABOi) cardiac transplantation is now used widely in infants with isohemagglutinin titers1:4, but there is increasing evidence that ABOi transplantation can also be used in children with significantly higher titers. We reviewed our high-titer ABOi transplants and report our results here.Patients who underwent ABOi cardiac transplantation from 2000 to 2013 with pre-existing isohemagglutinin titers of ≥1:16 were identified from departmental databases. Outcomes were reviewed using medical and laboratory records.Thirty patients underwent ABOi cardiac transplantation between 2000 and 2013. Twelve (40%) had pre-transplant isohemagglutinin titers of ≥1:16 and were included for further study. Median age was 14.9 (range 9.8 to 107.3) months and median weight was 9.6 (range 7.6 to 25) kg. Five (42%) were male. Pre-transplant diagnosis was cardiomyopathy in 8 of 12 (67%) and congenital heart disease in 4 of 12 (33%). Highest pre-transplant isohemagglutinin titer was 1:256 in 2 patients. Four patients (33%) had early antibody-mediated rejection (AMR), all within 15 days post-transplant. Management included use of rituximab, bortezomib, immunoadsorption and eculizumab. Three patients died but no deaths were associated with high isohemagglutinin titers.ABOi cardiac transplantation in patients with isohemagglutinin titers ≥1:16 is possible. AMR may occur early and immunoadsorption has proven effective at decreasing antibody titers.

Background To date, there have been no studies evaluating the effect of isolated lipoprotein(a) (Lp(a)) lowering therapy on carotid atherosclerosis progression. Methods We enrolled 30 patients who had coronary heart disease (CHD) verified by angiography, Lp(a) level ≥50 mg/dL, and low density lipoprotein cholesterol (LDL-C) level ≤2.6 mmol/L (100 mg/dL) on chronic statin therapy. Subjects were allocated in a 1:1 ratio to receive apheresis treatment on a weekly basis with immunoadsorption columns ("Lp(a) Lipopak" ® , POCARD Ltd., Russia) added to atorvastatin, or atorvastatin monotherapy. The primary efficacy end-point was the change from baseline in the mean intima-media thickness (IMT) of the common carotid arteries. Results After one month run-in period with stable atorvastatin dose, LDL-C level was 2.3 ± 0.3 mmol/L and Lp(a) – 105 ± 37 mg/dL. As a result of acute effect of specific Lp(a) apheresis procedures, Lp(a) level decreased by an average of 73 ± 12% to a mean of 29 ± 16 mg/dL, and mean LDL-C decreased by 17 ± 3% to a mean of 1.8 ± 0.2 mmol/L. In the apheresis group, changes in carotid IMT at 9 and 18 months from baseline were −0.03 ± 0.09 mm (p = 0.05) and −0.07 ± 0.15 mm (p = 0.01), respectively. In the atorvastatin group no significant changes in lipid and lipoprotein parameters as well as in carotid IMT were received over 18-month period. Two years after study termination carotid IMT increased by an average of 0.02 ± 0.08 mm in apheresis group and by 0.06 ± 0.10 mm in the control group (p = 0.033). Conclusion Isolated extracorporeal Lp(a) elimination over an 18 months period produced regression of carotid intima–media thickness in stable CHD patients with high Lp(a) levels. This effect was maintained for two years after the end of study. Trial Registration: Clinicaltrials.gov (NCT02133807).

Introduction Rare cases of pregnancy in women with homozygous familial hypercholesterolemia (HFH) have been reported. HFH might pose significant risks for the mother and her fetus. Statins, the most potent agents for low-density lipoprotein (LDL) cholesterol reduction, are contraindicated; thus lipoprotein apheresis remains the only effective treatment. Case report We report on a 34-year-old pregnant woman with HFH who was treated throughout the entire pregnancy by lipoprotein apheresis (immunoadsorption method). Increasing levels of LDL-cholesterol were stabilized at 9–10 mmol/L by lipoprotein apheresis (performed every 10 days). No complications were observed during the treatment procedures. Monitoring of the fetus revealed no impairment of the umbilical cord and blood flow in the uterine arteries, as well as no intrauterine growth retardation. The delivery was spontaneous and the child was breastfed for two months. Conclusion Intensive treatment by lipoprotein apheresis is an effective and safe therapeutic strategy during pregnancy, even in severe cases of HFH, as it can stabilize progressively increasing lipoprotein levels and prevent severe complications.

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.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 concentration5% an immunosuppressive treatment (IT) consisting of cyclophosphamide 1-2 mg/kg BW/d and/or prednisolone 1-2 mg/kg BW/d was initiated.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.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.

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.

Antibodies against MuSK seem to be the pathogenic factor in approximately 5–8% of myasthenia gravis (MG) patients. We aim to develop an antigen-specific therapy in which only MuSK antibodies will be removed from patients' plasma using MuSK extracellular domain (MuSK-ECD) as immunoadsorbent. We showed that two different immunoadsorbents, very efficiently and selectively depleted the MuSK antibodies from all tested sera, were stable during the procedure and were reusable. Furthermore, animal experiments showed that the treatment has no toxic effects to the animals. We conclude that the MuSK-ECD-mediated immunoadsorption can be used as an efficient antigen-specific therapy for MuSK-MG.

The development of immunoadsorbents that have high specificity for immunoglobulin and no immunogenicity is essential for immunoadsorption treatment of autoimmune diseases. In this study, we designed peptide immunoadsorbents by molecular grafting of the IgG-Fc binding epitopes of Protein A onto a de novo-designed helix-loop-helix peptide. Linear (linG7A5) and cyclic (cyG7A5) grafted peptides were synthesized to test their binding affinity and specificity. Peptide cyG7A5 demonstrated high specificity for human IgG-Fc, with a K(D) of 19 μM, and demonstrated no affinity to other plasma proteins, human serum albumin, or fibrinogen. To evaluate their immunoadsorbance efficiency, the grafted peptides and Protein A were conjugated to polyvinyl acetate resin and tested in a batch-wise process for adsorption removal of IgG from human plasma. The IgG capture capacities of the peptides correlated well with their binding affinities. Interestingly, cyG7A5 showed a higher binding specificity for IgG than did Protein A.

Traditional chromatographic techniques used in downstream processes of biomolecule manufacturing are often time-consuming and expensive. In this study, a cost-effective microporous micro-capillary film (MMCF) composed of ethylenevinyl alcohol (EVOH) was evaluated for its potential application in immunoadsorption with high process efficiency. A peptide ligand Ac-Phe-Tyr-His-Glu (Ac-FYHE) was immobilized on the inner surface of MMCF for selective binding of human immunoglobulin (hIgG). The porous structure and chemical properties of the prepared MMCF were confirmed by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). hIgG (2 mg/ml) adsorption studies demonstrated that the binding process followed a Langmuir isotherm with equilibrium adsorption capacities of 9.31 and 3.47 mg/ml adsorbent under static and dynamic conditions, respectively. Moreover, the membrane showed good flowrate tolerance when studied under flowrates of 0.5 ml/min to 10 ml/min. hIgG purity was 88.2% when obtained from an hIgG (2 mg/ml) and HSA (8 mg/ml) mixture and the purity remained over 80.0% when hIgG concentrations increased in the mixtures. Moreover, purity of 82.3% was achieved when removing hIgG directly from human serum. The MMCF-Ac-FYHE affinity column is expected to selectively remove hIgG from blood for the treatment of autoimmune diseases with high efficiency and cost effectiveness.

Purpose Antibody-mediated rejection (AMR) after heart transplantation (HTX) is associated with adverse outcomes . A standardized therapeutic regimen has not yet been defined. Immunoadsorption (IA) has shown promising results in AMR after kidney transplantation . We present our results with IA for acute symptomatic AMR after HTX. Methods This retrospective single-center study included all consecutive patients with proven and treated symptomatic AMR between 2006 and 2016. Survival from AMR, incidence of cardiac allograft vasculopathy (CAV) as well as donor specific anti-HLA-antibody (DSA) cumulative mean fluorescence intensity (MFI) assessed by LUMINEX single antigen bead assay are described. Results 22 patients were designated to undergo extracorporeal antibody removal for symptomatic AMR and received IA (n=18, 81,8 %) or plasmapheresis (PP; n=1, 4,5 %). One patient was switched to IA after one initial PP. In two patients IA/PP was not initiated due to unfavorable prognosis. Concomitant therapy was methylprednisolone (100 %), IVIg (9 %) and rituximab (4,5 %). AMR occurred after a median of 5.65 months (IQR 0.43-21.4) from HTX. Overall survival after a median follow up of 4.85 years from AMR diagnosis was 63.6 %. Mortality 30 days, 1 year and 5 years after AMR onset was 27.3 %, 31.8 % and 31.8 %. 4 patients (18.2 %) developed severe CAV (ISHLT grade ≥ 2) after a median time of 30.5 months after AMR onset. 21 patients had positive DSA at the time of AMR diagnosis (HLA I only: 13.6 %, HLA II only: 50 %, HLA I+II: 31.8%). Conclusion Despite high early mortality, long-term outcome of patients surviving the acute phase is encouraging, however we observed an increased burden of CAV. Due to the oftentimes fulminant clinical course, rapid diagnosis and therapy, facilitated by close interdisciplinary cooperation of intensivists , cardiac surgeons and nephrologists is crucial. Next steps include a detailed characterization of DSAs over the treatment period as well as endomyocardial biopsy specimens of patients with AMR.

Patients of clinically amyopathic dermatomyositis associated with rapidly progressive interstitial pneumonia (CADM-RFIP) with positive anti-MDA5 antibody usually presents rapid deterioration and traditional therapy such as cyclophosphamide combined with high-dose prednisone pulse therapy shows no clear benefit at whiles. However, blood purification combined with traditional therapy works according to the literature. We herein report two CADM-RFIP patients administered with DNA immunoadsorption combined with traditional therapy and then reviewed the literature of blood purification in CADM-RFIP patients at home and abroad to date. We emphasize blood purification such as DNA immunoadsorption could apply in the early stage of CADM-RFIP, which can decrease inflammation and allow us more time to control the condition better. Keywords: anti-MDA5 body, CADM, DNA immunoadsorption, Interstitial lung disease

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.

Autoimmune ion channel disorders of the peripheral nervous system include myasthenia gravis, the Lambert–Eaton myasthenic syndrome, acquired neuromyotonia and autoimmune autonomic ganglionopathies. These disorders are characterized by the common feature of being mediated by IgG autoantibodies against identified target antigens, i.e. the acetylcholine receptor, the voltage-gated calcium and potassium channels, and the neuronal acetylcholine receptor. Moreover, experimental animal models have been identified for these diseases that respond to immunotherapy and are improved by plasmapheresis. On this basis, autoimmune ion channel disorders represent the ideal candidate for therapeutic apheresis. Immunoadsorption can be the treatment of choice when intensive apheretic protocols or long-term treatments must be performed, in patients needing frequent apheresis to keep a stable clinical condition, in case of unresponsiveness to corticosteroids and immunosuppressive treatments, or failure with TPE or intravenous immunoglobulins, and in patients with severe contraindications to long-term corticosteroids.

Background and methods Adipocyte fatty acid-binding protein (FABP4) is a member of the intracellular lipid-binding protein family highly expressed in adipocytes and macrophages. Recent studies indicate a key role for circulating FABP4 in the pathogenesis of atherosclerosis and type 2 diabetes. We described an additional role for FABP4 in the development of cardiac dysfunction in obesity. Therefore, FABP4 seems to be a target in the prevention and treatment of metabolic and cardiovascular disorders in obesity with high potential for future therapeutic applications. However, a safe pharmacological therapy is not yet available. Lipoprotein apheresis is an established therapy for severe and otherwise untreatable hypercholesterolemia which increases life expectancy in patients at high-risk for cardiovascular events. We therefore investigated the acute effect of lipoprotein apheresis on FABP4 serum levels in 64 high-risk patients (25 women, 39 men) under regular apheresis treatment. Results FABP4 levels were significantly reduced by 23.2 ± 1.8% by apheresis treatment. Although women had higher FABP4 levels than men (53.5 ± 8.3 ng/ml vs. 30.7 ± 4.3 ng/ml), reduction rate after lipoprotein apheresis was similar in both genders. Among the apheresis methods investigated, immunoadsorption of lipoproteins was most effective in lowering circulating FABP4. Conclusion These data suggest that the reduction of FABP4 serum levels may contribute to the preventive effect of lipoprotein apheresis on cardiovascular events.

Objective Due to increasing waiting times for deceased donor kidneys, living donor kidney transplantation is increasingly performed in the presence of donor-specific antibodies (DSA). Methods Twenty-three patients with Luminex-detected DSA were successfully desensitized by anti-CD20 therapy and immunoadsorption ( N = 19) or plasmapheresis ( N = 4) and received a kidney transplant from a living donor. Twelve of the 23 patients (52%) had a positive CDC and/or ELISA crossmatch result before desensitization. Six patients were negative in CDC as well as ELISA screening but positive in Luminex for DSA. Results The 23 patients received a median of 8 apheresis treatments before and 5 treatments after transplantation. Induction therapy was performed with either thymoglobulin ( N = 11) or basiliximab ( N = 12). The 2-year graft survival rate was 100%. At last follow up, a median of 12 months after transplantation, median serum creatinine was 1.42 mg/dL, median MDRD-GFR 59.5 mL/min/1.73 m 2 , and median urinary protein-to-creatinine ratio 0.12. Ten out of fourteen patients (71%) who had completed the first year after transplantation by the time of analysis had no DSA by day 360. Acute T-cell mediated rejection was diagnosed in one patient (4%), and antibody-mediated changes were found in 5 patients (22%). Four out of these 5 patients showed evidence of persistent ( N = 2) or reemerging plus/minus de novo DSA ( N = 2) on day 360, and the 2 patients with persistent DSA lost their allograft subsequently on days 750 and 810, respectively. Infectious complications were infrequent. Conclusions Our previously described treatment algorithm for desensitization of living donor kidney transplant recipients with DSA results in good graft outcomes with a low rate of side effects.

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.

Currently, there are two major options for the successful and timely transplantation of sensitized kidney transplant recipients: (1) avoidance of the sensitization barrier using special allocation programs, or (2) desensitization. In the case of broadly sensitized kidney patients, a combination of both options might be necessary. This review focuses on new advances in desensitization of crossmatch-positive kidney transplant recipients which include immunoadsorption and the administration of new substances such as the complement C5 inhibitor eculizumab. Finally, integrated algorithms that combine different measures are acknowledged.

The presence of anti-nuclear antibodies (ANA) is a hallmark of systemic autoimmune rheumatic diseases (SARD). The indirect immunofluorescence (IIF) assay on HEp-2 cells is a commonly used test for the detection of ANA and was recently recommended as the screening test of choice by a task force of the American College of Rheumatology. However, up to 20% of serum samples from healthy individuals (HI) have been reported to have a positive ANA test, the majority of which are directed to the dense fine speckles 70 (DFS70) antigen. Even more important, the DFS IIF pattern has been reported in 33% of ANA positive HI, but not in ANA positive SARD sera. Since the intended use of the ANA HEp-2 test is to aid in the diagnosis of SARD, the reporting of anti-DFS70 antibodies and their associated pattern (DFS) as a positive test, significantly reduces the specificity and the positive likelihood of the ANA test. This has significant implications for diagnostic algorithms involving the detection of ANA. We summarize the current knowledge of anti-DFS70 antibodies and their impact on ANA testing. We also suggest a test algorithm which considers the DFS pattern and the presence of anti-DFS70 antibodies. In addition, we describe a novel method based on immunoadsorption of anti-DFS70 antibodies, which increases the specificity of the ANA HEp-2 test for SARD and which has the potential to overcome a significant limitation of the ANA HEp-2 assay.