Clinical Use and Therapeutic Potential of IVIG/SCIG, Plasma-Derived IgA or IgM, and Other Alternative Immunoglobulin Preparations

Intravenous and subcutaneous immunoglobulin preparations, consisting of IgG class antibodies, are increasingly used to treat a broad range of pathological conditions, including humoral immune deficiencies, as well as acute and chronic inflammatory or autoimmune disorders. A plethora of Fab- or Fc-mediated immune regulatory mechanisms has been described that might act separately or in concert, depending on pathogenesis or stage of clinical condition. Attempts have been undertaken to improve the efficacy of polyclonal IgG preparations, including the identification of relevant subfractions, mild chemical modification of molecules, or modification of carbohydrate side chains. Furthermore, plasma-derived IgA or IgM preparations may exhibit characteristics that might be exploited therapeutically. The need for improved treatment strategies without increase in plasma demand is a goal and might be achieved by more optimal use of plasma-derived proteins, including the IgA and the IgM fractions. This article provides an overview on the current knowledge and future strategies to improve the efficacy of regular IgG preparations and discusses the potential of human plasma-derived IgA, IgM, and preparations composed of mixtures of IgG, IgA, and IgM

Climate change, ecosystems and smallholder agriculture in Central America: an introduction to the special issue

Central America is one of the regions most exposed to climate change (Giorgi 2006). A narrow isthmus between the Pacific Ocean and the Caribbean Sea, it is strongly affected by droughts, hurricanes and the El Niño-southern oscillation (ENSO) phenomena (CEPAL 2011). As a result, three countries in the region rank in the top 10 of the Global Climate Risk Index (Kreft and Eckstien 2013) based on the impacts of extreme weather events between 1993 and 2012.Much of the regional economy is based on agriculture. In Guatemala, Honduras and Nicaragua, more than two thirds of the population depends on agriculture. This agricultural base is often intimately tied to ecosystems, especially in diverse farming systems of smallholders. But it is increasingly threatened by climate variability and change (Bouroncle et al. 2016; Baca et al. 2014), which are inducing changes in areas suitable for crops and leading to high yield variability. Storms, floods and droughts have had the greatest impacts on agriculture in Central America over the last century (Guha-Sapir et al. 2014). This special issue addresses the adaptation challenges facing smallholders, ecosystems and ecosystem services in the region. In this introduction, we review the literature on regional climate and its drivers, climate change projections, impacts on agriculture and ecosystems, and information management for adaptation in the region. Short descriptions of the special issue contributions are provided throughout the text.Universidad de Costa Rica/[805-B6-143]/UCR/Costa RicaUniversidad de Costa Rica/[805-A9-532]/UCR/Costa RicaUniversidad de Costa Rica/[805-B4-227]/UCR/Costa RicaUniversidad de Costa Rica/[805-B0-065]/UCR/Costa RicaUniversidad de Costa Rica/[805-B0-810]/UCR/Costa RicaUniversidad de Costa Rica/[805-A4-906]/UCR/Costa RicaUniversidad de Costa Rica/[805-B6-143]/UCR/Costa RicaUniversidad de Costa Rica/[805-A9-532]/UCR/Costa RicaUniversidad de Costa Rica/[805-B4-227]/UCR/Costa RicaUniversidad de Costa Rica/[805-B0-065]/UCR/Costa RicaUniversidad de Costa Rica/[805-B0-810]/UCR/Costa RicaUniversidad de Costa Rica/[805-A4-906]/UCR/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones Geofísicas (CIGEFI)UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de FísicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Ciencias del Mar y Limnología (CIMAR

Pharmacokinetic and pharmacodynamic effects of high-dose monoclonal antibody therapy in a rat model of immune thrombocytopenia

Intravenous administration of pooled, polyvalent human immunoglobulin (IVIG) has been used for over 20 years as a therapy for immune thrombocytopenia (ITP). IVIG is available in limited quantities, and clinical preparations have been associated with the transfer of human pathogens. We have proposed that high-dose monoclonal antibody may be used in lieu of IVIG to achieve beneficial effects in the treatment of ITP. The current study investigates the effects of high-dose monoclonal antibody therapy in a rat model of ITP. Hybridoma cells secreting a murine monoclonal antiplatelet antibody (7E3) and murine monoclonal anti-methotrexate IgG (AMI) were grown in serum-free media. Next, 7E3, 8 mg kg−1, was administered intravenously to rats following pretreatment with saline or AMI (1 g kg−1 IV). AMI and 7E3 plasma concentrations were determined via enzyme-linked immunosorbent assay, and platelet count was determined with a Cell-Dyne hematology analyzer. Severe, transient thrombocytopenia was induced by 7E3. Platelet counts dropped to ≈8% of initial values within 1 hour after 7E3 administration. AMI pretreatment dramatically affected 7E3-induced thrombocytopenia, significantly altering the time course of throm-bocytopenia (P<.05) and significantly decreasing the severity of 7E3-induced thrombocytopenia (ie, following AMI pretreatment, nadir platelet count was greater than 8-fold that of the control group,P<.05). In addition, AMI pretreatment induced a 57% increase in 7E3 clearance (1.13±0.13 mL h−1 kg−1 vs 0.72±0.08 mL h−1 kg−1,P<.05). Consequently, high-dose monoclonal antibody therapy attenuated thrombocytopenia and produced a moderate increase in the clearance of antiplatelet antibodies in a rat model of ITP