RESUMEN
BACKGROUND: Intravenous (IV) iron preparations are widely used in the treatment of anemia in patients undergoing hemodialysis (HD). All IV iron preparations carry a risk of causing hypersensitivity reactions. However, the pathophysiological mechanism is poorly understood. We hypothesize that a relevant number of these reactions are mediated by complement activation, resulting in a pseudo-anaphylactic clinical picture known as complement activation-related pseudo allergy (CARPA). METHODS: First, the in-vitro complement-activating capacity was determined for 5 commonly used IV iron preparations using functional complement assays for the 3 pathways. Additionally, the preparations were tested in an ex-vivo model using the whole blood of healthy volunteers and HD patients. Lastly, in-vivo complement activation was tested for one preparation in HD patients. RESULTS: In the in-vitro assays, iron dextran, and ferric carboxymaltose caused complement activation, which was only possible under alternative pathway conditions. Iron sucrose may interact with complement proteins, but did not activate complement in-vitro. In the ex-vivo assay, iron dextran significantly induced complement activation in the blood of healthy volunteers and HD patients. Furthermore, in the ex-vivo assay, ferric carboxymaltose and iron sucrose only caused significant complement activation in the blood of HD patients. No in-vitro or ex-vivo complement activation was found for ferumoxytol and iron isomaltoside. IV iron therapy with ferric carboxymaltose in HD patients did not lead to significant in-vivo complement activation. CONCLUSION: This study provides evidence that iron dextran and ferric carboxymaltose have complement-activating capacities in-vitro, and hypersensitivity reactions to these drugs could be CARPA-mediated.
Asunto(s)
Anemia Ferropénica/tratamiento farmacológico , Activación de Complemento/efectos de los fármacos , Hematínicos/farmacología , Compuestos de Hierro/farmacología , Fallo Renal Crónico/terapia , Administración Intravenosa , Anemia Ferropénica/complicaciones , Complemento C1q/efectos de los fármacos , Complemento C1q/metabolismo , Complemento C3d/efectos de los fármacos , Complemento C3d/metabolismo , Complejo de Ataque a Membrana del Sistema Complemento/efectos de los fármacos , Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Disacáridos/farmacología , Disacáridos/uso terapéutico , Compuestos Férricos/farmacología , Compuestos Férricos/uso terapéutico , Sacarato de Óxido Férrico , Óxido Ferrosoférrico/farmacología , Óxido Ferrosoférrico/uso terapéutico , Ácido Glucárico/farmacología , Ácido Glucárico/uso terapéutico , Hematínicos/uso terapéutico , Humanos , Técnicas In Vitro , Compuestos de Hierro/uso terapéutico , Complejo Hierro-Dextran/farmacología , Complejo Hierro-Dextran/uso terapéutico , Fallo Renal Crónico/complicaciones , Maltosa/análogos & derivados , Maltosa/farmacología , Maltosa/uso terapéutico , Lectina de Unión a Manosa/efectos de los fármacos , Lectina de Unión a Manosa/metabolismo , Properdina/efectos de los fármacos , Properdina/metabolismo , Diálisis RenalRESUMEN
UNLABELLED: The immunomodulating effects of two Echinacea species, E. purpurea and E. angustifolia and larch arabinogalactan extracted from Larix occidentalis were examined in a randomized, double-blind, placebo-controlled, prospective four-week clinical trial at a naturopathic medical school research center. SUBJECTS/MATERIALS: Forty-eight healthy female volunteers (22-51 y) were randomly assigned to one of six groups: standardized extract of E. purpurea (EP); ultra-refined E. purpurea/E. angustifolia (urEPA); E. purpurea/E. angustifolia (EPA); E. purpurea/E. angustifolia plus larch arabinogalactan (EPALA); larch arabinogalactan (LA); or placebo. METHODS: Immunological tests with enumerative measurements, stool cultures for Lactobacillus acidophilus and yeast, and health-related quality of life (HRQoL) using the Medical Outcomes Study derived SF-36 self-administered questionnaire were assessed at baseline and at four weeks. RESULTS: Complement properdin increased by 21 percent in the EPA group (p<0.05) and by 18 percent in the EPALA group (p<0.05), compared to the placebo group (p>0.05). SF-36 showed improvements in overall physical health, vitality, and emotional health in the same two groups (EPA and EPALA). DISCUSSION: Volunteers in the EPA and EPALA groups had increased production of complement properdin after four weeks of intervention. The increased complement properdin may be an indication of one aspect of immune system stimulation in patients treated with either E. purpurea/E. angustifolia or E. purpurea/E. angustifolia plus larch arabinogalactan.