Treatment of familial hypocholesterolemia by means of specific immunoadsorption

Borberg, H.; Gaczkowski, A.; Hombach, Vinzenz; Oette, K.; Stoffel, Wilhelm

doi:10.1002/jca.2920040204

Cited by 53 publications

(16 citation statements)

References 3 publications

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“…The results observed for immunoaffinity membranes containing PEG in this in vitro study are similar to the working capacity of 2-3 mg/ml of column volume reported for immunoaffinity columns in ex vivo studies [18,39]. However, a membrane system, with its superior transport properties, can be significantly smaller than current columns because it can be operated with much shorter cycle time.…”

Section: Discussionsupporting

confidence: 68%

“…Immunoadsorptive therapy for hypercholesterolemia is currently conducted in a treatment session lasting 3-4 h [18]. Each adsorptive cycle consists of four distinct steps: (1) perfuse the device with plasma; (2) rinse plasma from the device; (3) elute the adsorbed LDL, and (4) rinse out the elution buffer.…”

Section: Discussionmentioning

confidence: 99%

“…In this example, L is the treatment goal in terms of cholesterol removal in a single therapeutic session. The plasma LDL concentration in patients with untreated familial hypercholesterolemia may range from 300 to 600 mg/dl [18,29], but the plasma LDL concentration in a patient receiving regular immunoadsorption treatments is approximately 300 mg/dl immediately prior to treatment and about 100 mg/dl after treatment [18,41]. To decrease the plasma concentration from 300 to 100 mg/dl requires the removal of 5.6 g LDL cholesterol in a 70-kg patient.…”

Section: Example Therapy Systemmentioning

confidence: 99%

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In vitro Characterization of a Membrane-Based Low-Density Lipoprotein Affinity Adsorption Device

Soltys

Etzel²

1998

Blood Purif

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The objective of this study was to explore the use of microporous membranes as an alternative substrate to porous beads in affinity adsorption of low-density lipoprotein (LDL) for therapeutic purposes. Flat sheet immunoaffinity membranes containing a polyclonal antibody preparation were utilized as the affinity substrate. The antibody was covalently immobilized to the surface through a poly(ethylene glycol) (PEG) spacer. Equilibrium adsorption of LDL from plasma was measured. Adsorption from plasma and elution of bound LDL using citrate buffer were studied as a function of flow rate.Specific capacity was as great as 2 mg apolipoprotein B per milliliter membrane volume. The superior transport properties of the membrane allowed rapid adsorption and regeneration, which translated to a large number of adsorptive cycles that can be performed within a given treatment time. On the basis of in vitro performance characteristics, it is estimated that an immunoaffinity membrane device can provide a reduction in patient plasma LDL concentration comparable to that provided by packed columns, but with almost an 80% reduction in the device volume.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Example Therapy Systemmentioning

confidence: 99%

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In vitro Characterization of a Membrane-Based Low-Density Lipoprotein Affinity Adsorption Device

Soltys

Etzel²

1998

Blood Purif

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“…Patients with familial hypercholesterolemia are characterized by considerably increased plasma low-density lipoprotein (LDL) cholesterol levels, early development of atherosclerosis, and rapid progression of the disease. Conventional lipid-lowering therapy is virtually ineffective in all subjects with homozygous FH and in about 10-20% of those with the severe heterozygous form [3,9]. Thus specific LDL apheresis seemed to be an appropriate therapeutic alternative for both groups.…”

Section: Abstract: Familial Hypercholesterolemia -Ldl Apheresis -Cormentioning

confidence: 99%

The effect of LDL apheresis on progression of coronary artery disease in patients with familial hypercholesterolemia

et al. 1994

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This study investigated the effect of extracorporal lipid-lowering therapy by low-density lipoprotein (LDL) apheresis on coronary artery disease in a population characterized by early development and rapid progression of atherosclerosis. We treated 32 patients aged between 15 and 63 years with drug-refractory familial hypercholesterolemia, treated once a week by immuno-specific LDL apheresis for 3 years in a controlled prospective and non-randomized trial; 25 patients (14 females and 11 males) completed the study. Noninvasive data were obtained by physical examination, 12-lead ECG and exercise testing. Invasive cardiological data were obtained by cardiac catheterization according to a standardized protocol in four cardiological centers. Left ventricular ejection fraction was calculated using planimetry. Coronary stenoses were measured quantitatively in 23 defined coronary segments by a panel of four investigators with an electronic digital caliper. In addition, overall coronary atherosclerosis was visually qualified. Final decisions on a classification into one of three groups (regression, no change, progression) of coronary atherosclerosis were based on panel consensus. Six cardiac events occurred throughout the study: percutaneous transluminal coronary angioplasty in one patient, coronary bypass grafting in three and two deaths. Statistical analysis of exercise testing yielded no significant change for maximum power and work capacity during the study period. Hemodynamic data revealed no significant change; mean ejection fraction was calculated as 65.8 +/- 15.9% at study entry and 67.0 +/- 12.7% at completion. Quantitative measurement of 111 circumscribed coronary stenoses showed a mean stenosis degree of 45 +/- 26% at entry cineangio-film and 43 +/- 22% at final cineangio-film demonstrating no significant change.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Several types of immunoadsorbent columns, used clinically in tandem with a continuous-flow cell separator, have been developed to remove plasma proteins selectively from the circulation. For example, immunoadsorbent columns containing immobilized monoclonal anti-lipoprotein antibodies (mAbs) have been used successfully to treat individuals with severe congenital hyperlipidaemias [16,17], by repeated plasmapheresis and selective removal of low-density lipoprotein (LDL) particles from the blood. Moreover, recent advances in apheresis techniques based on the use of macrobead columns (e.g.…”

Section: Introductionmentioning

confidence: 99%

Exploring the feasibility of selective depletion of T lymphocyte subsets by whole blood immunoadsorption cytapheresis

Belák¹,

Valeri

Wright³

2007

Clinical and Experimental Immunology

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SummaryNormal turnover of T lymphocytes is slow relative to other blood cells. Consequently, the physical removal of circulating leucocytes by thoracic duct drainage, repeated leukapheresis or blood filtration results in T cell depletion and immunosuppression. However, clinical use of such procedures is impractical compared with immunosuppressive drugs or radiation. None the less, immunosuppression by physical depletion of T cells, avoiding the systemic toxicities of drugs and radiation, might have clinical advantages if immunophenotypically distinct T cell subsets could be depleted selectively. Recent advances in targeted plasma protein apheresis using adsorbent macrobead columns prompted us to determine whether analogous techniques might permit CD4+ T lymphocytes to be removed selectively from whole blood. To explore this possibility, we linked murine anti-human-CD4 and isotypeidentical control monoclonal antibodies (mAbs) to agarose, polyacrylamide and polystyrene macrobeads (150-350 mm) and then evaluated the selectivity, specificity and efficiency of macrobead columns to remove CD4 + T cells from anti-coagulated whole blood at varying mAb densities and flow rates. We also examined saturation kinetics and Fc-oriention versus random coupling of mAbs to macrobeads. Sepharose 6MB macrobead (250-350 mm) columns proved to be most effective, selectively removing up to 98% of CD4 + T cells from whole blood. Moreover, depletion efficiency and selectivity were retained when these columns were reused after elution of adherent CD4 + cells. These studies indicate that selective depletion of T lymphocyte subsets by whole blood immunoadsorption apheresis using mAb-linked macrobead columns may be feasible on a clinical scale. It is possible that such apheresis techniques could achieve targeted forms of immunosuppression not possible with drugs or radiation.

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Treatment of familial hypocholesterolemia by means of specific immunoadsorption

Cited by 53 publications

References 3 publications

In vitro Characterization of a Membrane-Based Low-Density Lipoprotein Affinity Adsorption Device

In vitro Characterization of a Membrane-Based Low-Density Lipoprotein Affinity Adsorption Device

The effect of LDL apheresis on progression of coronary artery disease in patients with familial hypercholesterolemia

Exploring the feasibility of selective depletion of T lymphocyte subsets by whole blood immunoadsorption cytapheresis

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