Contamination of therapeutic human immunoglobulin preparations with apolipoprotein <scp>H</scp> (β2‐glycoprotein I)

Lackner, F; Beck, G.; Eichmeir, Stephanie; Gemeiner, Manfred; Hummel, Karin Anna; Pullirsch, Dieter; Razzazi-Fazeli, Ebrahim; Seifner, Alexandra; Miller, Ingrid

doi:10.1002/elps.201300319

Cited by 5 publications

(2 citation statements)

References 19 publications

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“…Unfortunately, immunoglobulins and other blood-derived products are not typical drugs, since plasma processing into various types of products is highly specialized. Large-scale processing (fractionation) is very important for ensuring quality and safety profiles of the products [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Passive blood anaphylaxis: subcutaneous immunoglobulins are a cause of ongoing passive anaphylactic reaction

Zdziarski

Gamian

Majda³

et al. 2017

Allergy Asthma Clin Immunol

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BackgroundAllergic, especially anaphylactic, reactions during immunoglobulin replacement therapy are rare, but their pathophysiology and classification remain ambiguous. Recent findings show positive results of skin tests with commercially available immunoglobulins, but target antigens and responsible compounds of the tested immunoglobulins have not been strictly identified.Case description and findingsFour adult patients with recently diagnosed common variable immunodeficiency qualified for standard subcutaneous immunoglobulin replacement therapy regimen. They had no history of receiving immunoglobulins, blood or blood product transfusions. Edema, confluent wheals and erythema were observed at the site of subcutaneous immunoglobulin infusion: typical early and late phase reaction. A transient increase in various passively transferred IgG and IgE antibodies was responsible for misleading positive outcome of the serological testing for active humoral response such as type I allergy, anti-Rh, isohemagglutinins and rheumatoid factor (RF). Although the clinical presentation was very unusual and severe, the retrospective analysis showed no isohemagglutinins, RF and IgE in the patients’ serum before but it was positive after the infusion (median IgE = 18 IU/ml, RF = 8 IU/ml). Type I allergic reaction (laryngeal edema, rhinoconjuctivitis) came out at +14 days of replacement therapy when the patient visited countryside. In the second patient anaphylactic reaction was observed 5 days after ScIg administration, and only when the patient consumed peanuts. Therefore, IgE concentration was measured retrospectively in a series of commercial preparations used in the initial subcutaneous immunoglobulin replacement therapy that caused the adverse event (AE) and it was determined between 138 and 232 IU/ml (kU/l), i.e. 690–2100 IU per g of protein. Specific IgE was within a wide range from 198 (mix of food) to 2809 kUA/l (mix of grass) but many of the tested allergen-specific IgE were class 2 or 3 (i.e. 0.71–17.5 kUA/l).ConclusionsThe case resembles passive cutaneous anaphylaxis and Prausnitz–Küstner reaction but clinical significance of the classical phenomena has not yet been described. This observation indicates that anaphylactic reactions during immunoglobulin replacement therapy may result from IgE or pathological IgG content. Such IgE presence was sporadically reported (34.5–105 IU/ml, i.e. 862.5–1450 IU/g of protein) in intravenous immunoglobulins that are used and monitored by healthcare professionals. In clinical practice the definition of adverse events is inadequate since individual batches of immunoglobulins come with different specificity therefore, they should be classified as transfusion products (not bioequivalents). Such new approach implies establishing (1) new control methods and strategies to ensure introduction of the safety regulations for subcutaneous home self-administration of immunoglobulins as well as (2) guidelines for the prevention of anaphylaxis in patients receiving immunoglobulins (for example peanut).

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Section: Discussionmentioning

confidence: 99%

Passive blood anaphylaxis: subcutaneous immunoglobulins are a cause of ongoing passive anaphylactic reaction

Zdziarski

Gamian

Majda³

et al. 2017

Allergy Asthma Clin Immunol

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“…Non-IgG proteins in IVIg have been associated with adverse events; the best documented example is the association of FXIa with thromboembolism in recalled lots of Octagam [ 47 ]. β2-glycoprotein, one of the proteins identified as slightly elevated in Privigen in this study, has also been discussed as a potential risk factor for thromboembolism [ 47 , 48 ]. An article by Sridhar et al examined literature from 2008 to 2012 that detailed adverse events associated with IVIg use [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

High-resolution physicochemical characterization of different intravenous immunoglobulin products

Washburn

Meccariello

et al. 2017

PLoS ONE

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Intravenous immunoglobulin (IVIg) is a complex mixture drug comprising diverse immunoglobulins and non–IgG proteins purified from the plasma of thousands of healthy donors. Approved IVIg products on the market differ regarding source of plasma, isolation process, and formulation. These products are used widely, and often interchangeably, for the treatment of immunodeficiency and autoimmune and inflammatory diseases, but their mechanisms of action in different indications are not well understood. A primary limitation to understanding the therapeutic relevance of specific components within IVIg has been the limited resolution of analytics historically implemented to characterize its complex mixture. In this study, high-resolution analytics were applied to better understand the composition of IVIg and product variations. We characterized three approved IVIg products: Gammagard®, Privigen®, and Octagam®. Differences in the distribution of molecular weight species, IgG sequence variants, isoforms, glycoforms, and the repertoire of previously reported antibody specificities were identified. We also compared the effect of aging on these products to identify changes in size distribution and posttranslational modifications. This type of characterization may provide insights into the specific factors and components of IVIg that may influence its activity and ultimately lead to optimization of IVIg products for use in autoimmune diseases.

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Blood, Blood Components, Plasma and Plasma Products

Kreuter

Hagan

2014

Side Effects of Drugs Annual

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Contamination of therapeutic human immunoglobulin preparations with apolipoprotein H (β2‐glycoprotein I)

Cited by 5 publications

References 19 publications

Passive blood anaphylaxis: subcutaneous immunoglobulins are a cause of ongoing passive anaphylactic reaction

Passive blood anaphylaxis: subcutaneous immunoglobulins are a cause of ongoing passive anaphylactic reaction

High-resolution physicochemical characterization of different intravenous immunoglobulin products

Blood, Blood Components, Plasma and Plasma Products

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