Cuamba I, Santano R, Grau-Pujol B, Vidal M, Aguilar R, et al.
BMC medicine •
Clearance of Plasmodium falciparum infection requires a T1 immune response with production of pro-inflammatory cytokines, IgG1, and IgG3 responses. In contrast, infections with helminths are dominated by T2/T immune responses characterized by production of anti-inflammatory cytokines, IgE, and IgG4, which could potentially interfere with malaria outcomes and immune responses. We recruited 441 malaria-symptomatic children aged 2-10 years attending two hospitals in the Manhiça District (Mozambique) and assessed infection by rapid antigen diagnostic test, microscopy, and/or quantitative PCR. Using Luminex, we measured concentrations of 30 cytokines and IgA, IgM, IgE, IgG, and IgG1-4 levels against 12 P. falciparum antigens and total IgE. Among 74 children diagnosed with malaria, 22% (16) were coinfected with STH, and 78% (58) had only P. falciparum. Soil-transmitted helminths (STH) coinfection associated with lower P. falciparum density (P = 0.005) and fever (P = 0.047). Coinfected children also had lower concentrations of plasma pro-inflammatory (IL-8, TNF, IFNα, IP-10, MCP1, MIG, MIP1β, and GM-CSF) and anti-inflammatory cytokines (IL-5, IL-10) (P < 0.05). Furthermore, antibody responses to a set of P. falciparum antigens, including SSP2 (IgG1, IgG4, IgG), PTRAMP (IgG3), MSP3 (IgG), RH5 (IgG1), and α-gal (IgG1), as well as total IgE, were elevated in STH coinfected children (P < 0.05). STH infections were associated with decreased P. falciparum parasitemia, downregulation of inflammatory cytokines, and enhanced antibody responses, potentially resulting in milder malaria episodes, suggesting enhanced protective immunity.
Montoya AL, Carvajal EG, Ortega-Rodriguez U, Estevao IL, Ashmus RA, et al.
Molecules (Basel, Switzerland) •
Chagas disease (CD) is caused by the parasite and affects 6-7 million people worldwide. The diagnosis is still challenging, due to extensive parasite diversity encompassing seven genotypes (TcI-VI and Tcbat) with diverse ecoepidemiological, biological, and pathological traits. Chemotherapeutic intervention is usually effective but associated with severe adverse events. The development of safer, more effective therapies is hampered by the lack of biomarker(s) (BMKs) for the early assessment of therapeutic outcomes. The mammal-dwelling trypomastigote parasite stage expresses glycosylphosphatidylinositol-anchored mucins (tGPI-MUC), whose -glycans are mostly branched with terminal, nonreducing α-galactopyranosyl (α-Gal) glycotopes. These are absent in humans, and thus highly immunogenic and inducers of specific CD anti-α-Gal antibodies. In search for α-Gal-based BMKs, here we describe the synthesis of neoglycoprotein NGP11b, comprised of a carrier protein decorated with the branched trisaccharide Galα(1,2)[Galα(1,6)]Galβ. By chemiluminescent immunoassay using sera/plasma from chronic CD (CCD) patients from Venezuela and Mexico and healthy controls, NGP11b exhibited sensitivity and specificity similar to that of tGPI-MUC from genotype TcI, predominant in those countries. Preliminary evaluation of CCD patients subjected to chemotherapy showed a significant reduction in anti-α-Gal antibody reactivity to NGP11b. Our data indicated that NGP11b is a potential BMK for diagnosis and treatment assessment in CCD patients.
Ortega-Rodriguez U, Portillo S, Ashmus RA, Duran JA, Schocker NS, et al.
Methods in molecular biology (Clifton, N.J.) •
Chagas disease (ChD), caused by the protozoan parasite Trypanosoma cruzi, affects millions of people worldwide. Chemotherapy is restricted to two drugs, which are partially effective and may cause severe side effects, leading to cessation of treatment in a significant number of patients. Currently, there are no biomarkers to assess therapeutic efficacy of these drugs in the chronic stage. Moreover, no preventive or therapeutic vaccines are available. In this chapter, we describe the purification of Trypanosoma cruzi trypomastigote-derived glycosylphosphatidylinositol (GPI)-anchored mucins (tGPI-mucins) for their use as antigens for the reliable primary or confirmatory diagnosis and as prognostic biomarkers for early assessment of cure following ChD chemotherapy. We also describe, as an example, the synthesis of a potential tGPI-mucin-derived α-Gal-terminating glycan and its coupling to a carrier protein for use as diagnostic and prognostic biomarker in ChD.
Aguilar R, Ubillos I, Vidal M, Balanza N, Crespo N, et al.
Scientific reports •
Naturally-acquired antibody responses to malaria parasites are not only directed to protein antigens but also to carbohydrates on the surface of Plasmodium protozoa. Immunoglobulin M responses to α-galactose (α-Gal) (Galα1-3Galβ1-4GlcNAc-R)-containing glycoconjugates have been associated with protection from P. falciparum infection and, as a result, these molecules are under consideration as vaccine targets; however there are limited field studies in endemic populations. We assessed a wide breadth of isotype and subclass antibody response to α-Gal in children from Mozambique (South East Africa) and Ghana (West Africa) by quantitative suspension array technology. We showed that anti-α-Gal IgM, IgG and IgG levels vary mainly depending on the age of the child, and also differ in magnitude in the two sites. At an individual level, the intensity of malaria exposure to P. falciparum and maternally-transferred antibodies affected the magnitude of α-Gal responses. There was evidence for a possible protective role of anti-α-Gal IgG3 and IgG4 antibodies. However, the most consistent findings were that the magnitude of IgM responses to α-Gal was associated with protection against clinical malaria over a one-year follow up period, especially in the first months of life, while IgG levels correlated with malaria risk.