Hypotension with intravenous immunoglobulin therapy: importance of pH and dimer formation

Kroez, Monika; Kanzy, E. J.; Gronski, P; Dickneite, Gerhard

doi:10.1016/j.biologicals.2003.09.001

Cited by 42 publications

(30 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most importantly, however, the new formulation is stabilized by a novel approach being based on the excipients nicotinamide, L-proline, and L-isoleucine. IgG molecules in concentrated solutions have the tendency to form dimers which induce hypotension in a rat model and can provoke headache, nausea, and fever in humans if present in excessive concentrations [5][6][7]. Dimer formation is inhibited by three amphiphilic stabilizers which are natural constituents of the human body.…”

Section: Discussionmentioning

confidence: 99%

“…These compounds reduce IgG dimer formation during storage. It has previously been shown that IgG preparations with a high dimer content were poorly tolerated [5][6][7]. Nanofiltration was introduced as an additional physical virus removal step, which also effectively contributes to the removal of the transmissible spongiform encephalopathy (TSE) agents in experimental models [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical Properties of a Novel Liquid Intravenous Immunoglobulin: Studies in Patients with Immune Thrombocytopenic Purpura and Primary Immunodeficiencies

Borte¹,

Davies²,

Touraine³

et al. 2004

Transfus Med Hemother

View full text Add to dashboard Cite

Background: We have developed a novel liquid intravenous immunoglobulin (IVIG-F10). It consists of a nanofiltered 12% immunoglobulin G (IgG) solution, stabilized with nicotinamide, L-proline and L-isoleucine. The efficacy, tolerability, safety, and pharmacokinetics of this product were assessed in patients with chronic immune thrombocytopenic purpura (ITP) and primary humoral immunodeficiencies (PID). Patients and Methods: 33 chronic ITP patients with platelet counts of < 20 × 10⁹/l were treated with IVIG-F10 or Sandoglobulin at doses of 0.4 g/kg body weight on 5 consecutive days. The primary efficacy endpoint was an increase in platelet counts to ≧50 × 10⁹/l. Secondary endpoints were time to and duration of platelet response and regression of bleeding. 34 PID patients with X-linked agammaglobulinemia, common variable immunodeficiency or IgG subclass deficiency were treated for 6 months with IVIG-F10 or Sandoglobulin at doses of 0.3–0.8 g/kg, infused at 3- or 4-week intervals. The primary efficacy endpoint was the number of days absent from school/work. Secondary endpoints were feeling of well-being, days of hospitalization, and use of antibiotics. Results: In ITP patients, the primary endpoint was met by 12/16 patients on IVIG-F10 and by 12/17 patients on Sandoglobulin (p = 1.000). Results of the secondary endpoints were comparable in the two study groups. In the PID study, 10/17 patients on IVIG-F10 and 9/17 patients on Sandoglobulin missed days at school/work, with monthly mean absences of 0.7 and 0.6 days (p = 0.746), respectively. There were no significant differences in the outcome of the secondary endpoints. Pharmacokinetics showed constant peak and trough serum IgG levels in PID patients. The median half-life (t_1/2) of IgG was 33 days in the IVIG-F10 group and 41 days in the Sandoglobulin group. For anti-HBsAg, median t_1/2 values were shorter, i.e. 17 and 19 days for IVIG-F10 and Sandoglobulin, respectively. In the ITP study, adverse events related to study drug were suspected in 9 and 14 patients treated with IVIG-F10 and Sandoglobulin, respectively; in the PID study adverse events occurred in 8 and 9 patients, respectively. Viral safety was ascertained in both studies by serology supplemented with nucleic acid amplification testing. Serum levels of the stabilizers transiently increased after infusion of IVIG-F10, but were back to baseline at the following day. Conclusions: The clinical studies in patients with chronic ITP and PID showed that the efficacy, tolerability, safety, and pharmacokinetics of IVIG-F10 were comparable to the properties of Sandoglobulin.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical Properties of a Novel Liquid Intravenous Immunoglobulin: Studies in Patients with Immune Thrombocytopenic Purpura and Primary Immunodeficiencies

Borte¹,

Davies²,

Touraine³

et al. 2004

Transfus Med Hemother

View full text Add to dashboard Cite

show abstract

“…IgG dimerization and aggregate formation was also associated with an increase in the risk of adverse effects (Kroez et al, 2003). These aggregates bind and activate components of the complementary system and routine determination of anticomplementary activity was therefore adopted.…”

Section: Resultsmentioning

confidence: 99%

Production of intravenous human dengue immunoglobulin from Brazilian-blood donors

Gouveia

Oliveira

Lucena³

et al. 2013

Braz. J. Pharm. Sci.

View full text Add to dashboard Cite

Dengue represents an important health problem in Brazil and therefore there is a great need to develop a vaccine or treatment. The neutralization of the dengue virus by a specific antibody can potentially be applied to therapy. The present paper describes, for the first time, the preparation of Immunoglobulin specific for the dengue virus (anti-DENV IgG), collected from screened Brazilian blood-donations. Production was performed using the classic Cohn-Oncley process with minor modifications. The anti-DENV IgG was biochemically and biophysically characterized and fulfilled the requirements defined by the European Pharmacopoeia. The finished product was able to neutralize different virus serotypes (DENV-1, DENV-2, and DENV-3), while a commercial IgG collected from American blood donations was found to have low anti-dengue antibody titers. Overall, this anti-DENV IgG represents an important step in the study of the therapeutic potential and safety of a specific antibody that neutralizes the dengue virus in humans.Uniterms:. Viral infections. Dengue/treatment. Dengue/virus/neutralization. Immunoglobulins/ preparation. Plasma fractionation. Virus neutralization.A dengue representa um importante problema de saúde no Brasil, portanto, a identificação de vacina ou tratamento eficaz é uma necessidade urgente. A neutralização do vírus da dengue, por anticorpo específico, tem potencial aplicação terapêutica. Descrevemos aqui, pela primeira vez, a preparação de imunoglobulina específica para o vírus da dengue (IgG anti-DENV), produzida a partir do plasma selecionado de doadores brasileiros. A produção foi realizada utilizando o método clássico de Cohn-Oncley com pequenas modificações. A IgG anti-DENV foi bioquimicamente e biofisicamente caracterizada e cumpriu os requisitos definidos pela Farmacopeia Europeia. O produto final foi capaz de neutralizar diferentes sorotipos do vírus (DENV-1, DENV-2 e DENV-3), enquanto que a IgG comercial, produzida a partir do plasma de doadores americanos, apresentou baixos títulos de anticorpos anti-dengue. No geral, esta IgG anti-DENV representa uma importante etapa para o estudo do potencial terapêutico e segurança da neutralização, por anticorpos específicos, do vírus da dengue em humanos.Unitermos: Infecções virais. Dengue/tratamento. Dengue/vírus/neutralização. Imunoglobulinas específicas/preparação. Fracionamento de plasma. Neutralização viral. INTRODUCTIONThere are around 2.5 billion people living in areas endemic for dengue fever and it is estimated that there are 100 million infections annually (Gubler 1998). The burden of dengue in endemic countries weighs heaviest on children. However, there has been an increasing trend towards adult infection in certain countries (Ooi, Goh, Gubler, 2006;Cummings et al., 2009). Most travelers with dengue have been adults (Wilder-Smith, Schwartz, 2005). Currently, neither cure nor vaccines are available, and new therapies are thus urgently needed. Although there have been considerable developments in medicinal chemistry, no promising small-organic...

show abstract

“…Apparently IVIG with high dimer content is passing ACA release criterion because dimers are poor complement activators, 76 while dimers apparently induce release of pro-inflammatory cytokines, particularly TNF leading to severe adverse events in recipients. 36,77 On the one hand the challenge for the fractionating industry is to limit dimer/oligomer formation over the shelf-life of a product without removal of IgG molecules potentially able to form dimers because the IgG molecules able to form dimers might harbor a particular fraction of IgG, including NAbs, and Id/anti-Id dimers might be of advantage for the treatment of autoimmune and inflammatory diseases. Recently it emerged that the fraction of dimers in IVIG apparently have enriched some properties usually considered being of benefit for patients affected by autoimmune and inflammatory diseases [78][79][80] or for patients needing first-line defense because of infection.…”

Section: Nabs and Dimers In Ivigmentioning

confidence: 99%

Naturally Occurring Antibodies/Autoantibodies in Polyclonal Immunoglobulin Concentrates

Späth

Lutz

2012

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

It was a long way from the use of hyperimmune animal sera for the treatment of toxin-producing infections to the production of polyclonal, polyspecific human immunoglobulin preparations and the use of NAbs as therapeutic tools for autoimmune and inflammatory diseases. Some highlights of the development of knowledge in blood fractionation techniques, basic science and clinical wisdom are reviewed in this chapter. Proudly we mention the outstanding contribution of Swiss scientists and clinicians in the development of IVIG as clinical tool for some otherwise untreatable diseases or taking advantage of its low adverse event profile in long-term treatment of other chronic autoimmune and inflammatory diseases. This chapter summarizes some of the characteristics and the effects in humans of NAbs which are present in IgG concentrates. We call attention to the fact that the human data remain, at least in part, incomplete, among others because even with the most efficient large-scale techniques available not more than approximately 50% of the total IgG in plasma can be fractionated into an immunoglobulin G concentrate.

show abstract

Hypotension with intravenous immunoglobulin therapy: importance of pH and dimer formation

Cited by 42 publications

References 19 publications

Clinical Properties of a Novel Liquid Intravenous Immunoglobulin: Studies in Patients with Immune Thrombocytopenic Purpura and Primary Immunodeficiencies

Clinical Properties of a Novel Liquid Intravenous Immunoglobulin: Studies in Patients with Immune Thrombocytopenic Purpura and Primary Immunodeficiencies

Production of intravenous human dengue immunoglobulin from Brazilian-blood donors

Naturally Occurring Antibodies/Autoantibodies in Polyclonal Immunoglobulin Concentrates

Contact Info

Product

Resources

About