Immunoadsorption Procedures Research Articles

Pure red cell aplasia among ABO mismatched hematopoietic stem cell transplant recipients: a 13-years retrospective study and literature review.

Pure red cell aplasia (PRCA) is a possible complication after allogeneic hematopoietic stem cell transplantation (HSCT) with major ABO incompatibility. Patients experience delayed engraftment of the erythroid series, with prolonged transfusion-dependent anemia and iron overload. We performed a revision of the most recent literature about post-HSCT PRCA treatment procedures. Moreover, we conducted a retrospective study, over the last 13-years, which included all consecutive major ABO mismatched HSCT performed in our unit, with the aim to assess PRCA incidence, risk factors, and response to different treatments. Overall, 194 patients received a major ABO mismatched transplant from 2010 to 2022. For each patient, data about demographic and transplant characteristics, engraftment, blood transfusion, and possible treatment received were collected. The literature review returned 23 eligible papers on PRCA treatment, with high success rate using plasma-exchange (PEX) and immunoadsorption procedures, daratumumab, and eltrombopag. Our study identified a total of 24 cases of PRCA. Among risk factors for PRCA development, we have found older recipient age (p=0.01), high pre-HSCT IgG and IgM IHA titer (p<0.0001), major rather than bidirectional ABO incompatibility (p=0.02), low T CD8 lymphocyte count in the graft (p=0.006), relative donor (p=0.02) and bone marrow as stem cell source (p=0.002). However, multivariate analysis confirmed only pre-HSCT IgG IHA titer as the unique risk factor for PRCA occurrence. The optimal cut-off value of pre-HSCT IgG IHA for PRCA development, resulted to be 1/64, with a 100% sensitivity and 68.8% specificity (p<0.0001). All patients with PRCA had received rhEPO and transfusion support and 20 patients received additional treatments like PEX, rituximab, and more recently daratumumab. Comprehensively, PEX and rituximab obtained a response in half of the cases, at a variable time, while the few cases of patients we treated with daratumumab suggest promising results. The overall response rate in our cohort was 75%, with significantly better survival (94.4% vs. 16.7%) and lower transplant-related mortality (6.3% vs. 80%) for PRCA responders. Standardized guidelines on when and how to treat PRCA are necessary because the current treatment is controversial among centers.

Immuno-Hematologic Complexity of ABO-Incompatible Allogeneic HSC Transplantation.

ABO incompatibility is not considered a contraindication for hematopoietic stem cell transplantation (HSCT). Approximately 30% of transplants from related donors and up to 50% of transplants from unrelated donors are ABO incompatible. Immuno-hematologic investigations allow to estimate donor/recipient ABO mismatch and anti-A/B isohemagglutinin (IHA) titration in the pre-HSCT phase. Immediate hemolysis or delayed complications (passenger lymphocyte syndrome and pure red cell aplasia) can occur post HSCT. Some preventive measures take into consideration either decision-making algorithms based on the recipient's IHA titration or clinical protocols for the removal/reduction of IHAs through plasma exchange or immunoadsorption procedures. Product manipulation through red blood cell (RBC) and/or plasma depletion can also be taken into account. Currently, the best approach in the management of ABO-incompatible transplant is not defined in expert consensus documents or with solid evidence. In addition, the methods for IHA titration are not standardized. A transfusion strategy must consider both the donor's and recipient's blood group systems until the RBC engraftment catches on and ABO conversion (forward and reverse typing) is confirmed on two consecutive and independent samples. Therefore, ABO incompatibility in HSCT represents a demanding immuno-hematologic challenge and requires all necessary preventive measures, including the appropriate selection of ABO blood components for transfusion.

Immunoadsorption therapy in refractory heart failure patients with dilated cardiomyopathy: a potential therapeutic option

Removal of cardiac autoantibodies by immunoadsorption might confer clinical improvement in dilated cardiomyopathy. In this pilot study, we investigated the efficacy and safety of immunoadsorption therapy in refractory heart failure patients with dilated cardiomyopathy. This study consisted of 9 heart failure patients with dilated cardiomyopathy, NYHA III-IV, left ventricular ejection fraction <30%, unresponsive to heart failure therapy, and with cardiac autoantibodies. Patients underwent immunoadsorption therapy for five consecutive days using a tryptophan column. Changes in cardiac function (left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-systolic diameter), exercise capacity (6-minute walk distance), neurohormonal (N-terminal pro-brain natriuretic peptide), proinflammatory (high-sensitive C-reactive protein), and myocardial (cardiac troponin-I), biochemical, and hematological variables were obtained at baseline and after 3 and 6 months of immunoadsorption therapy. Mean left ventricular ejection fraction and 6-minute walk distance significantly increased at 3 months (from 23.27±5.09 to 32.1±1.7%, p=0.01 for left ventricular ejection fraction and from 353±118 to 434±159 m, p=0.04 for 6-minute walk distance) and further increased at 6 months after immunoadsorption therapy (to 34.5±7.7%, p=0.02 for ejection fraction and to 441±136 m, p=0.04 for 6-minute walk distance). NT-proBNP level reduced from 1161(392.8-3034) to 385(116.1-656.5) ng/L (p=0.04), and high-sensitive C-reactive protein decreased from 9.74±0.96 to 4.3±5.8 mg/L (p=0.04) at 6 months. Left ventricular end-diastolic diameter (66.1±5.8 vs. 64.7±8.9 mm) and left ventricular end-systolic diameter (56.1±8.6 vs. 52.3±10.8 mm) tended to decrease but did not reach statistical significance. No significant worsening was observed in creatinine, cardiac troponin-I, and hemoglobin levels after the immunoadsorption procedure. In dilated cardiomyopathy patients with refractory heart failure, immunoadsorption may be considered a potentially useful therapeutic option to improve a patient's clinical status.

Immunoadsorption for Treatment of Patients with Suspected Alzheimer Dementia and Agonistic Autoantibodies against Alpha1a-Adrenoceptor-Rationale and Design of the IMAD Pilot Study.

Background: agonistic autoantibodies (agAABs) against G protein-coupled receptors (GPCR) have been linked to cardiovascular disease. In dementia patients, GPCR-agAABs against the α1- and ß2-adrenoceptors (α1AR- and ß2AR) were found at a prevalence of 50%. Elimination of agAABs by immunoadsorption (IA) was successfully applied in cardiovascular disease. The IMAD trial (Efficacy of immunoadsorption for treatment of persons with Alzheimer dementia and agonistic autoantibodies against alpha1A-adrenoceptor) investigates whether the removal of α1AR-AABs by a 5-day IA procedure has a positive effect (improvement or non-deterioration) on changes of hemodynamic, cognitive, vascular and metabolic parameters in patients with suspected Alzheimer’s clinical syndrome within a one-year follow-up period. Methods: the IMAD trial is designed as an exploratory monocentric interventional trial corresponding to a proof-of-concept phase-IIa study. If cognition capacity of eligible patients scores 19–26 in the Mini Mental State Examination (MMSE), patients are tested for the presence of agAABs by an enzyme-linked immunosorbent assay (ELISA)-based method, followed by a bioassay-based confirmation test, further screening and treatment with IA and intravenous immunoglobulin G (IgG) replacement. We aim to include 15 patients with IA/IgG and to complete follow-up data from at least 12 patients. The primary outcome parameter of the study is uncorrected mean cerebral perfusion measured in mL/min/100 gr of brain tissue determined by magnetic resonance imaging with arterial spin labeling after 12 months. Conclusion: IMAD is an important pilot study that will analyze whether the removal of α1AR-agAABs by immunoadsorption in α1AR-agAAB-positive patients with suspected Alzheimer’s clinical syndrome may slow the progression of dementia and/or may improve vascular functional parameters.

Therapeutic apheresis in ABO-incompatible kidney and liver transplantation: A single-center experience of 50 patients.

ABO antigens play an important role in solid organ transplantation. Desensitization for ABO incompatibility offers patients awaiting transplant a larger donor pool. The aim of this study was to assess outcome of desensitization using the institutional preconditioning protocol in ABO-incompatible solid organ transplants. A retrospective analysis of ABO-incompatible solid organ transplants between October 2015 and June 2018, at a tertiary healthcare center was performed. The preconditioning regimen consisted of immunosuppression and therapeutic apheresis (TA). Pre- and post-TA titers were performed, until a target titer of 8 or below was achieved, at which transplant was performed. Follow-up data till 1 year was analyzed. A total of 50 ABO-incompatible solid organ transplantations, including 14 liver transplants and 36 renal transplants were analyzed. The median baseline anti-A and anti-B titers were 192 and 256, respectively. A total of 150 therapeutic plasma exchange (TPE) procedures were performed for renal transplant recipients; 19 TPE and eight immunoadsorption procedures (five preoperative and three intraoperative) were performed for liver transplant recipients. Five (10%) patients experienced minor adverse events. Biopsy revealed antibody-mediated rejection was observed in three cases in the immediate posttransplant phase and in three (6.67%) cases over 1 year. There was one death due to transplant-associated thrombotic microangiopathy. Graft survival for renal transplant was 100% and death-censored graft survival for liver transplant was 100%. Despite difficulties, ABO-incompatible transplants can be performed without antibody-mediated rejection with the use of an appropriate protocol.

Immunoadsorption for Treatment of Antibody Mediated Rejection after Lung Transplantation

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. 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. 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. 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.

Immunoadsorption in ABO-incompatible kidney transplantation in adult and pediatric patients with follow-up on graft and patient survival: First series from India.

BACKGROUND:There are no published reports on desensitization protocol for ABO-incompatible kidney transplants using Immuno-Adsorption (IA) plasmapheresis from India. IA offers certain advantages including processing of larger plasma volumes, quicker reduction of isoagglutinin titers and no requirement of replacement fluids.AIMS AND OBJECTIVES:Authors' center evaluated success of desensitization protocol, and graft/patient outcomes when IA procedures were performed for desensitization in adult and pediatric ABO-incompatible kidney transplant patients.METHODS:Patients undergoing ABO-incompatible kidney transplant with use of IA were evaluated at tertiary care center in north India. Patient records for 2-years were collated from hospital information system (HIS) and procedure forms.RESULTS:Sixteen IA procedures were performed in five patients who underwent successful ABO-incompatible kidney transplant. Initial isoagglutinin IgG titer ranged from 32-512. Mean number of IA procedures performed to achieve the desired pre-transplant IgG titer ≤8 was 3.2. New IA column was used for each patient (and re-used for the same patient, if needed, after sterilization with Low temperature steam of formaldehyde). Mean plasma volume processed during each IA procedure was 4.5 times. No adverse events were observed during any IA procedure. All patients achieved successful desensitization. All patients continue to do well clinically with mean follow-up period of 8.8 months. Although IA was expensive, it offered advantages like specificity, larger plasma volume processing with desired reduction in titer, no 'replacement fluid' requirements and no adverse events in present case series.CONCLUSION:IA plasmapheresis was universally successful in decreasing the ABO-isoagglutinin titers to desired level in all prospective ABO incompatible kidney transplant patients.

Immunoadsorption enables successful rAAV5-mediated repeated hepatic gene delivery in nonhuman primates.

Adeno-associated virus (AAV)-based liver gene therapy has been shown to be clinically successful. However, the presence of circulating neutralizing antibodies (NABs) against AAV vector capsids remains a major challenge as it may prevent successful transduction of the target cells. Therefore, there is a need to develop strategies that would enable AAV-mediated gene delivery to patients with preexisting anti-AAV NABs. In the current study, the feasibility of using an immunoadsorption (IA) procedure for repeated, liver-targeted gene delivery in nonhuman primates was explored. The animals were administered IV with recombinant AAV5 (rAAV5) carrying the reporter gene human secreted embryonic alkaline phosphatase (hSEAP). Seven weeks after the first rAAV treatment, all of the animals were readministered with rAAV5 carrying the therapeutic hemophilia B gene human factor IX (hFIX). Half of the animals administered with rAAV5-hSEAP underwent IA prior to the second rAAV5 exposure. The transduction efficacies of rAAV5-hSEAP and rAAV5-hFIX were assessed by measuring the levels of hSEAP and hFIX proteins. Although no hFIX was detected after rAAV5-hFIX readministration without prior IA, all animals submitted to IA showed therapeutic levels of hFIX expression, and a threshold of anti-AAV5 NAB levels compatible with successful readministration was demonstrated. In summary, our data demonstrate that the use of a clinically applicable IA procedure enables successful readministration of an rAAV5-based gene transfer in a clinically relevant animal model. Finally, the analysis of anti-AAV NAB levels in human subjects submitted to IA confirmed the safety and efficacy of the procedure to reduce anti-AAV NABs. Furthermore, clinical translation was assessed using an immunoglobulin G assay as surrogate.

Therapeutic Immunoadsorption and Conventional Plasma Exchange in ABO-incompatible Renal Transplant: An Exculpatory Evidence.

AimThe objective of this study was to compare the efficacy of immunoadsorption (IA) with conventional therapeutic plasma-exchange (cTPE) in ABO-incompatible (ABOi) renal transplant.MethodsData of patients from July 2015 to June 2017 (category-I, number of patients (N) = 11; IA±cTPE) on the average length of stay (ALOS), number of cTPE/IA, antibody-titers (AT), creatinine, patient and graft survival at one year were compared retrospectively with patients in period from February 2012 to June 2015 (category-II, N = 29; cTPE only). AT of patients not decreasing to less than one fold after two cTPE were shifted for IA. For patients undergoing IA, real-time AT was done and IA stopped after target titer (TT <1:8) was achieved. Post-transplant cTPE was done if, titers rebounded to ≥1:8. Intravenous immunoglobulin (IVIG) was given after every cTPE/IA. Cost comparisons were made.ResultsIn category-I, seven patients (63.63%) were shifted to IA from cTPE. The mean cTPE procedures in category I and II are 3.5 ± 2.4 and 4.8 ± 2.5, respectively (p = 0.206). The mean IA procedures in category-I are 1.6 ± 0.5. The number of patients requiring post-operative TPE was less in category-I than category-II, i.e., N = 5, 45.5% vs N = 20, 69%, respectively (p = 0.171). The expense of IA in category-I vs cTPE in category-II was statistically not significant (p = 0.422) but had significant lesser ALOS (p = 0.044). Expenses, when a patient undergoes both cTPE and IA (category-I), are significantly higher to category-II (p = 0.003). The two groups were comparable in AT, creatinine value, graft and patient survival rates at one year.ConclusionContrary to the general judgment of IA being expensive than cTPE, this study shows equivalent expenditures with comparable therapeutic outcomes.

176 - Immunoadsorption procedures is feasible even with very low platelets count in order to restore a post-platelet transfusion increment

176 - Immunoadsorption procedures is feasible even with very low platelets count in order to restore a post-platelet transfusion increment

The Reuse of Immunoadsorption Columns in ABO-Incompatible Kidney Transplantation Is Efficient: The Swiss Experience.

We developed a multicentric Swiss protocol for ABO-incompatible kidney transplantation including immunoadsorption column reuse. The aim of this study was to assess efficacy and safety of immunoadsorption column reuse in ABO-incompatible kidney transplantation. We performed a multicentric prospective trial including all ABO-incompatible kidney transplantations in Switzerland from 2005 to 2011. Patients received rituximab and standardized immunosuppression with tacrolimus, mycophenolate mofetil, and steroids. Antigen-specific perioperative immunoadsorption was performed. Immunoadsorption columns were reused after restoration. Graft survival, patient survival, kidney function, rejections, number of columns, adverse events after column reuse, and anti-A/anti-B antibody titers were assessed. Seventy-one ABO-incompatible patients underwent antigen-specific immunoadsorption and could be transplanted across the blood group barrier. Kaplan-Meier estimates for both, patient-censored and death-censored graft survivals were both 97.2% at 5 years. Allograft function was excellent with a mean estimated glomerular filtration rate of 54 mL per min after 1 year. The median number of pretransplant immunoadsorptions was 5. All centers performed column reuse. A total of 394 immunoadsorption procedures were performed with reused filters. Patient survival, graft survival, and adverse events did not differ when filters were reused. Column reuse resulted in cost savings of 21,458 USD per patient. We have introduced a national protocol for ABO-incompatible kidney transplantation including immunoadsorption column reuse. Column reuse was efficient and safe.

The selective therapeutic apheresis procedures

Selective apheresis procedures have been developed to target specific molecules, antibodies, or cellular elements in a variety of diseases. The advantage of the selective apheresis procedures over conventional therapeutic plasmapheresis is preservation of other essential plasma components such as albumin, immunoglobulins, and clotting factors. These procedures are more commonly employed in Europe and Japan, and few are available in the USA. Apheresis procedures discussed in this review include the various technologies available for low-density lipoprotein (LDL) apheresis, double filtration plasmapheresis (DFPP), cryofiltration, immunoadsorption procedures, adsorption resins that process plasma, extracorporeal photopheresis, and leukocyte apheresis.

Bleeding complications in pediatric ABO-incompatible kidney transplantation

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

Impact of Pretransplant Intravenous Immunoglobulin Administration on Anti-AB0 Antibody Levels in AB0-Incompatible Living Donor Kidney Transplantation

Background From March 2007 to July 2010, we performed 14 AB0-incompatible (AB0i) living kidney transplantations using donor blood group-specific immunoadsorption (IA), anti-CD20 monoclonal antibody, and intravenous immunoglobulin (IVIG) pretreatment. Methods To analyze the effect of a presumed anti-donor blood group–specific antibody transfer by IVIG administration (0.5 g/kg; 5.4 ± 0.9 days pretransplant), we assessed AB0i antibody titers in different IVIG preparations and evaluated their impact on patient AB0i antibody titers. Results AB0i antibody IgG titers before treatment ranged from 8 to 1024. We performed 6.9 ± 1.1 IA procedures pretransplant to reach AB0i antibody titers ≤4, which enabled successful transplantation in all pretreated patients. Their mean serum creatinine at discharge was 1.5 ± 0.1 mg/dL. IVIG preparations differed profoundly in their AB0i antibody titers: The lowest titers were observed in Sandoglobulin preparations (1–8) compared with Intratect (2–128), Octagam (4–32) and Gamunex (2–512). Usually, administration of the IVIG preparation containing the lowest isoagglutinin titer resulted in low AB0i antibody titer increments in patient sera: Sandoglobulin, 2 titer steps ( n = 2), 1 titer step ( n = 1), and 0 titer steps ( n = 5). In contrast, Octagam showed 0 titer steps ( n = 2) and Intratect, 0 titer steps ( n = 3). However, after Gamunex administration, the AB0i antibody titer of 8 and the AB0i antibody titer rose 3 titer steps (16 to 128; n = 1), which could not be explained by passive transfer of isoagglutinin alone. Conclusion Our data showed that the choice of IVIG preparation with the lowest AB0i antibody levels is a time- and cost-sparing step in the pretreatment of AB0i living donor kidney recipients. Posttransplant, a high isoagglutinin content within the IVIG preparation has the potential to induce antibody-mediated rejection.

Recurrence of Nephrotic Proteinuria in Children With Focal Segmental Glomerulosclerosis After Renal Transplantation Treated With Plasmapheresis and Immunoadsorption: Case Reports

Idiopathic focal segmental glomerulosclerosis (FSGS) is believed to be caused by a circulating permeability factor. FSGS recurrence is common after transplantation. The treatment is still a matter of debate; plasmapheresis (PE) and immunoadsorption (IA) are often used. We report on PE and IA in the treatment of two children with recurrent nephrotic proteinuria. Patient 1 was a 16-year-old girl who had recurrence of nephrotic proteinuria on the first day after transplantation (proteinuria-19 g/d). Primary immunosuppressive therapy was changed to high-dose cyclosporine and cyclophosphamide; plasmapheresis was started on day 4. Altogether we performed 53 PE and 38 IA procedures. During the first month, PE procedures were performed with no more than a 2-day interval between sessions, and the girl achieved partial remission (proteinuria 3 g/d). PE was then stopped. After 2 months, a relapse of heavy proteinuria occurred. This relapse was successfully treated again with intensified PE treatment. After achieving remission, a chronic PE regimen was started (PE once a week), similar to the previous series. The child remained in partial remission. Seven months after renal transplantation, she was switched from PE to IA, because of severe hypoproteinemia. Graft biopsy performed at 4 months showed effacement of the foot processes. At the present time she has a good graft function and 3 g/d proteinuria. Patient 2 was a 13-year-old girl with FSGS since 9 years. On the second day after renal transplantation she developed nephrotic proteinuria (proteinuria-14 g/d), which was treated with 39 PE and 16 IA treatments. She went into complete remission on the intensified PE regimen, had one relapse, and was switched to chronic IA. Graft biopsy performed at 2 weeks after transplantation showed effacement of the foot processes. At the present time she has good graft function and low proteinuria (0.3 g/d). In conclusion, intensified PE or IA treatments induced remission of recurrent nephrotic range proteinuria. Chronic PE or IA can maintain patients with frequent relapses in long-term remission.

Anti-β1-adrenergic receptor autoantibodies in patients with chronic Chagas heart disease

Chronic Chagas heart disease (cChHD), a chronic manifestation of the Trypanosoma cruzi infection, is characterized by high antibody levels against the C-terminal region of the ribosomal P proteins (i.e. peptide R13, EEEDDDMGFGLFD) which bears similarity with the second extracellular loop of beta1-adrenergic receptor (beta1-AR, peptide H26R HWWRAESDEARRCYNDPKCCDFVTNR). Because it has not been demonstrated clearly that IgGs from cChHD patients bind to native human beta1-AR, the aim of this study was to investigate further the physical interaction between cChHD IgGs and the human beta1-AR. Immunofluorescence assays demonstrated the binding of these antibodies to the receptor expressed on stably transfected cells, together with a beta1-AR agonist-like effect. In addition, immunoadsorption of the serum samples from cChHD patients with a commercially available matrix, containing peptides representing the first and the second extracellular loop of the beta1-AR, completely abolished reactivity against the H26R peptide and the physiological response to the receptor. The follow-up of this specificity after in vitro immunoadsorption procedures suggests that this treatment might be used to diminish significantly the serum levels of anti-beta1-AR antibodies in patients with Chagas heart disease.

Immunoadsorption therapy and complement activation

Complement activation was studied in six patients treated with immunoadsorption columns Ig-ADSOPAK for myasthenia gravis. Mean therapy duration was 18.6 months (range 4–28 months). Prior and after each procedure, concentrations of C3 and C4 were examined, hemolytic activity of complement by a classic pathway (CH50) was determined, as well as terminal complement complex (TCC). After each immunoadsorption procedure, a decrease of C3 and C4 was noted (median 21.19% and 19.68%, respectively). The CH50 and TCC follow-up showed statistically significant complement activation. Median of TCC accrual was 60.21% and median of CH50 decrease was 23.24%. No clinical manifestations of complement activation were present. With increasing number of procedures a marked decrease of TCC activation was observed in five patients, which was statistically significant in three of them ( p < 0.05). This finding may indicate an immunomodulating effect of long-term adsorption therapy. With increasing number of procedures, an inhibition in complement system reactivity occurs. This result, however, has to be confirmed on a larger group of patients.

Changes of plasma proteins after immunoadsorption using Ig-Adsopak columns in patients with myasthenia gravis

Background and Objectives: Ig-Adsopak immunoadsorption columns were used for treatment to determine their influence on the amount of immunoglobulins and other plasma proteins. Patients and methods: Patients with myasthenia gravis were treated, 178 immunoadsorption procedures were performed. The mean plasma volume treated in a 2–4 week interval was 3600 ml. Plasma protein concentrations were measured prior to and after each treatment. The concentration of anti-acetylcholine receptor antibodies was also measured. Results: The amounts of the IgG, IgM and IgA removed were respectively, 55.7%, 42.8% and 43.4% of the initial level whereas the other plasma proteins were found to bind with a lower affinity with only 19.8% removal. 60.9% of the anti-acetylcholine receptor antibodies were removed. Conclusions: Ig-Adsopak collumns have a semi-specific effect on the plasma proteins, mostly on immunoglobulins of all classes.

Apheresis registry in Sweden: scope, techniques and indications for treatment. A report from the Swedish apheresis study group

Registries of therapeutic apheresis can be used to evaluate changes in technology, clinical indications and applications over the years. This study reports data collected prospectively and voluntarily in Sweden during 1993–1999. A total number of 40 apheresis units have been performing therapeutic apheresis procedures: 16 blood centers, 20 dialysis units, two intensive care units, one hematology ward and one hemotherapy unit. The registry includes a median of 92% of the centers for therapeutic apheresis in Sweden during the years and in 1999 there were 31 active units in 26 hospitals. The total numbers of procedures per year have remained fairly stable corresponding to a median of 46 treatments/100 000 inhabitants, and in 1999 4084 procedures were performed. The number of plasma exchanges has decreased, but LDL-apheresis and immunoadsorption procedures have increased over the years. 70% of the patients have been referred for 12 indications. A significant decline was found for patients with SLE and Guillain Barres syndrome. The use of extracorporeal photo-chemotherapy has increased over the years, and 3 indications include >75% of the patients. There has been an adaptation to the experience learned by different studies. The number of collections of hematopoietic progenitor cells is about 9/100 000 inhabitants, and in 1999 821 collections were performed. The use of allogeneic donors is increasing. The extent of therapeutic apheresis in Sweden was compared to other countries on the basis of published data. In Sweden, the extent of therapy is two- to three-fold to that for Canada and France.

Study of an anti-human transthyretin immunoadsorbent: Influence of coupling chemistry on binding capacity and ligand leakage

A variant of transthyretin (TTR Val30Met) has been identified as the main protein precursor of the amyloid fibrils deposited in familial amyloidotic polyneuropathy (FAP). Specific removal of TTR in an extracorporeal immunoadsorption procedure is currently under investigation as a possible treatment of FAP. Immunoadsorbents were constructed by immobilizing murine anti-TTR monoclonal antibody 88.6.BA9 onto agarose gel supports via several different coupling chemistries. The influence of coupling conditions such as pH and antibody density, and of perfusion variables, such as antigen concentration and applied flow-rate, on the TTR capture efficiency, was determined. Cyanogen bromide-, carbonyldiimidazole- and aldehyde-activated (ALD) supports conjugated with antibody at optimal pH, provided immunoadsorbents with comparable TTR binding capacities. Regarding stability, leakage was lowest for the ALD based immunoadsorbents, particularly at high pH.