Immunoadsorption In Patients Research Articles

Effects of protein A immunoadsorption in patients with chronic dilated cardiomyopathy

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

Complete Elimination of Cardiodepressant IgG3 Autoantibodies by Immunoadsorption in Patients With Severe Heart Failure

Cardiodepressant IgG3 autoantibodies (CD-Abs) can be targeted by apheresis. Using blinded measurements of CD-Abs before and after immunoadsorption (IA), the cardiac function of patients who did or did not achieve complete CD-Abs elimination was compared. Autoantibodies were completely removed from 18 patients with heart failure (New York Heart Association class 3 or 4, left ventricular ejection fraction (LVEF) <30%) using a selective IgG3 adsorption column. All patients had anti-beta1-adrenergic and/or M2-muscarinic autoantibodies before IA, and all LVEF were measured on radionuclide ventriculography. CD-Abs were measured before and after IA, and patient status was blinded until all measurements were collected. Treatment was defined as complete when CD-Abs status changed from positive to negative after IA. Other instances were defined as incomplete. Six-min walk test results and brain natriuretic peptide levels improved significantly after IA (P<0.01). The increase in LVEF 3 months after IA was significantly greater after complete treatment in comparison to the incomplete treatment group (19+/-8-29+/-9% vs 18+/-9-17+/-8%, P<0.01). Cardiac insufficiency events were also more frequent in the incomplete treatment group. Complete elimination of CD-Abs with apheresis may be related to improved cardiac function in the treatment of heart failure.

Immunoadsorption in patients with dilated cardiomyopathy

Abstract Dilated cardiomyopathy (DCM) is characterized by ventricular enlargement and progressive systolic and diastolic dysfunction. Disturbances of the cellular and humoral immune system are frequently observed in DCM. Circulating antibodies of the IgG class against diverse myocardial antigens have been identified and are thought to play a causative role in the pathogenesis of DCM. Possible mechanisms include the promotion of chronic inflammation, activation of the β1-adrenoreceptor and activation of Fc γ-receptors. Various clinical studies suggest a positive effect of immunoadsorption (IA) using protein A columns, with or without subsequent IgG substitution (IA/IgG) on symptoms, myocardial function and the hemodynamic situation of these patients. Decreased myocardial inflammation was also observed in DCM patients treated with IA/IgG. In addition to conservative medical treatment, IA/IgG may therefore represent a new therapeutic option for patients with heart failure due to DCM.

Effects of protein A immunoadsorption in patients with advanced chronic dilated cardiomyopathy

The objective of this study was to investigate functional effects of immunoadsorption (IA) in severely limited study patients with chronic nonfamilial dilated cardiomyopathy (DCM), and to analyze the prevalence of Troponin I (TNI) autoantibodies. Immunoadsorption (IA) has been shown to induce early hemodynamic improvement in patients with nonfamilial DCM. We performed IA using Immunosorba columns on five consecutive days in 27 patients with chronic DCM, congestive heart failure of NYHA class >or=II, left ventricular ejection fraction below 40%, and mean time since initial diagnosis of 7.2 +/- 6.8 years. Immediately after IA, IgG decreased by 87.7% and IgG3 by 58.5%. Median NT-pro BNP was reduced from 1740.0 ng/L at baseline to 1504.0 ng/L after 6 months (P = 0.004). Mean left ventricular ejection fraction (LVEF) was not significantly improved overall (24.1 +/- 7.8% to 25.4 +/- 10.4% after 6 months, P = 0.38), but LVEF improved >or=5% (absolute) in 9 of 27 (33%) patients. Bicycle spiroergometry showed a significant increase in exercise capacity from 73.7 +/- 29.4 Watts to 88.8 +/- 31.1 Watts (P = 0.003) after 6 months while VO2max rose from 13.7 +/- 3.8 to 14.9 +/- 3.0 mL/min kg after 6 months (P = 0.09). Subgroup analysis revealed a higher NT-pro BNP reduction in patients with shorter disease duration (P = 0.03) and without TNI autoantibodies at baseline (P = 0.05). All 9 patients with an absolute increase of LVEF of >or=5.0% were diabetic (P = 0.0001). In this study, on severely limited heart failure patients with nonfamilial DCM, IA therapy moderately improved markers of heart failure severity in a limited subgroup of patients. This may be due to the selected study population with end-stage heart failure patients and the lower reduction of IgG3 compared to previous studies. Future blinded multicenter studies are necessary to identify those patients that benefit most.

Clinical Examination About Immunoadsorption in Patients with Dilated Cardiomyopathy

Not only acute homodynamic but also chronic prognosis improvements were proved at the immunoadsorption (IA) in some patients with dilated cardiomyopathy (DCM). So we plan clinical examination about IA therapy for Japanese DCM patients (UMIN-CTR, Entry-No. 000000623), and want to introduce our protocol and preliminary data about this study.

Non-specific immunoadsorption in patients with dilated cardiomyopathy: Mechanisms and clinical effects

An association between viral myocarditis and DCM has been hypothesized for a subset of patients with DCM. In addition to abnormalities of the cellular immune system, disturbances of humoral immunity have been described in DCM patients. A number of antibodies against various cardiac cell proteins have been identified in DCM. The functional role of cardiac autoantibodies in DCM is under debate. Circulating antibodies are extractable by immunoadsorption (IA). IA has been successfully used for treatment of a number of autoimmune diseases. IA may also represent a therapeutic option for a subset of patients with DCM. Recent open controlled pilot studies showed that removal of circulating antibodies by IA induces improvement of cardiac function in DCM. IA, furthermore, decreases myocardial inflammation. In vitro data indicate that removal of negative inotropic antibodies may represent the essential mechanism of IA in DCM. These antibodies belong to immunoglobulin G subclass 3 and may play an important role in cardiac dysfunction of DCM patients. A larger, randomized, prospective, multi-centre study will be necessary to confirm therapeutic efficacy of IA therapy in DCM.

Cardiology patient page. Familial dilated cardiomyopathy.

Cardiology patient page. Familial dilated cardiomyopathy.

Immunoadsorption in systemic lupus erythematosus: different techniques and their current role in medical therapy.

In the last 30 years, several studies have documented the effect of plamapheresis and immunoadsorption in eliminating pathogenic autoantibodies (AB) and immune complexes (IC) from circulation of patients with systemic lupus erythematosus (SLE). However, these extracorporeal therapies are still not accepted as first line options, which may be because of existing controlled studies failing to confirm any obvious benefit. Immunoadsorption offers some advantages compared with plasmapheresis, but until today only the avoidance of any substitution fluids has really been used. The new therapeutic options given by immunoadsorbers--a continuous application in acute disease states or chronic use instead of immunosuppressive drugs--have still to be evaluated in systemic autoimmune diseases. To date published studies of immunoadsorption in patients with SLE reveal good efficacy in a majority of patients combined with excellent biocompatibility. Randomized controlled trials are mandatory to give continued support to the therapeutic opportunities offered only by immunoadsorption; the limited number of patients suitable for this therapy necessitates multicentric cooperation.

Development of an in vitro miniature model to simulate immunoadsorption in patients with systemic lupus erythematosus.

In SLE, immunoadsorption is used as an adjuvant therapy; however, adsorption profiles and binding mechanisms have not yet been completely investigated. Using a minicolumn filled with the sorbent IMPH with or without the ligand phenylalanine, we developed a model simulating clinical conditions in a reduced scale with a constant ratio of plasma to column volume and a constant plasma flow at room temperature. By desorbing the column, the adsorption efficacy for different antibodies could be measured directly. We demonstrate that the adsorption rate can be increased by a low plasma flow and by covering the column surface. Double perfusion of the same column did not increase the amount of adsorbed antibodies. We further demonstrate that the carrier material without a ligand is unable to bind antibodies or protein. In the IMPH sorbent anti-dsDNA antibodies were significantly better adsorbed than total IgG or total protein. After a single perfusion of 21 samples, we estimated a mean anti-dsDNA antibody adsorption rate of 22.5% (+/-13.6). A group of ten responders with a medium adsorption rate of 35.4% (+/-6.5) clearly differed from a second group of eleven nonresponders (10.9% +/- 4.2). Anti-cardiolipin antibodies (ACA) were adsorbed in a wide range (IgG type, 2.5-52.7%, IgM type, 1.1-37.8%) while anti-Ro (SSA) antibody adsorption was negligible. This in vitro minimodel provides a precise simulation of therapeutic immunoadsorption and helps to analyze the binding characteristics of the sorbent IMPH and shows its effectiveness in several antibody subsets of different patients.

Improvement of Cardiac Function after Immunoadsorption in Patients with Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is a myocardial disease characterized by progressive depression of myocardial contractile function and by ventricular dilatation. Abnormalities of the cellular and humoral immune system are present in patients with myocarditis and DCM. Various circulating cardiac autoantibodies have been detected among patients suffering from DCM. The relative contribution of cardiac antibodies to cardiac malfunction in DCM remains to be elucidated. Extraction of antibodies by immunoadsorption has been successfully used for treatment of various autoimmune diseases. In this review we report recent studies, which indicate that immunoadsorption improves cardiac function of patients with DCM. The data from these studies indicate that activation of the humoral immune system, with production of cardiac autoantibodies, may play a functional role in cardiac malfunction of patients with DCM.

Plasma Exchange or Immunoadsorption in Patients with Rapidly Progressive Crescentic Glomerulonephritis a Swedish Multi-Center Study

A therapeutic removal of antibodies may be achieved by immunoadsorption (IA) or by plasma exchange (PE). The aim of this prospective randomised study was to compare the efficacy of these different techniques with regard to treatment of patients with rapidly progressive glomerulonephritis (RPG) having at least 50% crescents. Forty-four patients with a RPG were included for treatment either by IA or PE (with albumin as substitution for removed plasma). All patients were additionally treated with immunosuppression. A median of 6 sessions of PEs were performed in 23 patients compared with 6 IAs in 21 patients. Goodpasture's syndrome (GP) was present in 6 patients (PE 3, IA 3). All of them started and ended in dialysis, two died. Among the remaining 38 patients (26 men, 12 women) 87% had antibodies to ANCA. Creatinine clearance for PE versus IA were at a median at start 17.1 and 19.8 ml/min, and at 6 months 49 and 49 ml/min, respectively. At 6 months 7 of 10 patients did not need dialysis (remaining: IA 0/5 and PE 2/5, n.s.). The extent of improvement did not differ between the groups. Three patients died during the observation period of 6 months (IA 2; PE 1, on HD). Although no difference was found between the IA or the PE group this study shows that the protocol used was associated with an improved renal function in most patients (except for Goodpasture's syndrome) whereas 70% of them could leave the dialysis program.

Five years' experience at one centre with protein A immunoadsorption in patients with deleterious allo/autoantibodies (anti-HLA antibodies, autoimmune bleeding disorders) and post-transplant patients relapsing with focal glomerular sclerosis.

Protein A is extracted from a strain of Staphylococcus aureus and binds specifically to the constant domains of immunoglobulins and possibly to fibronectin. It has already been shown that concentrations of all IgG isotypes (except IgG3) are efficiently decreased by immunoadsorption (IA) on protein A linked to sepharose beads. This system has been developed by Cobe-Excorim Co. to either remove IgG in some instances where they wil be harmful, i.e. allo- and autoantibodies inducing pathological conditions (autoimmune diseases, haematological disorders with allo/autoantibodies, anti-HLA antibodies in sensitized patients awaiting organ transplantation) or treat several immunological diseases with unknown pathogenesis. In our unit, 20 patients with high titres of anti-HLA panel-reactive antibodies, four patients with haematological disorders (haemophilia with anti-VIII antibodies and Glanzmann diseases) and three patients with post-transplant focal glomerular sclerosis (FGS) underwent IA over the past 5 years. Infectious complications were not observed after IA and the procedure was always well tolerated. In spite of the use of adjunctive immunosuppressive therapy with prednisone and cyclophosphamide, and although the reduction in serum IgG was close to 90%, the de novo synthesis of allo- and autoantibodies was important after IA procedures. In the cases of removal of anti-HLA antibodies, patients with a pre-IA antibody titre which was > 1:128 clearly did not benefit from the technique and other immunological criteria were not predictive of efficacy. Fourteen patients were transplanted, four with a well-matched kidney with both pre- and post-IA negative cross-matching, and 10 with a positive historical cross-match with the donor.(ABSTRACT TRUNCATED AT 250 WORDS)