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.
Juste RA, Ferreras-Colino E, de la Fuente J, DomĂnguez M, Risalde MA, et al.
Immunology •
Trained immunity (TRAIM) may be defined as a form of memory where innate immune cells such as monocytes, macrophages, dendritic and natural killer (NK) cells undergo an epigenetic reprogramming that enhances their primary defensive capabilities. Cross-pathogen protective TRAIM can be triggered in different hosts by exposure to live microbes or microbe-derived products such as heat-inactivated Mycobacterium bovis or with the glycan α-Gal to elicit protective responses against several pathogens. We review the TRAIM paradigm using two models representing distinct scales of immune sensitization: the whole bacterial cell and one of its building blocks, the polysaccharides or glycans. Observations point out to macrophage lytic capabilities and cytokine regulation as two key components in non-specific innate immune responses against infections. The study of the TRAIM response deserves attention to better characterize the evolution of host-pathogen cooperation both for identifying the aetiology of some diseases and for finding new therapeutic strategies. In this field, the zebrafish provides a convenient and complete biological system that could help to deepen in the knowledge of TRAIM-mediated mechanisms in pathogen-host interactions.
Sastre J, Aranda E, Grávalos C, Massutà B, Varella-Garcia M, et al.
Critical reviews in oncology/hematology •
to evaluate the efficacy and safety of first-line single-agent cetuximab in fit elderly patients with metastatic colorectal cancer, as well as potential molecular predictive factors for efficacy. patients aged 70 or older with metastatic CRC without criteria for frailty and no prior treatment for advanced disease were treated with single-agent cetuximab 400mg/m(2) followed by weekly 250mg/m(2) until disease progression or unacceptable toxicity. forty-one patients were included. Two patients achieved a complete response and 4 patients had a partial response for an overall response rate of 14.6%. Fifteen patients (36.6%) remained stable. Median time to progression was 2.9 months and median overall survival 11.1 months despite two-third of patients received chemotherapy at progression. Forty-five percent of EGFR gene copy number positive patients by FISH were progression-free at 12 weeks, in contrast with 12% of FISH negative patients (p=0.04). Grade 3 skin toxicity was reported in 5 patients (12.2%). Hypersensitivity infusion reactions were not reported and there were no toxic deaths. cetuximab is a safe monoclonal antibody with moderate activity in first-line metastatic colorectal cancer, but the present study does not support the use of cetuximab as single-agent in first-line fit elderly patients with metastatic CRC.
Meat allergy is rarely reported. Most of the described cases are sensitizations to bovine serum albumin. The aim of the study was to describe a case of allergy to a new meat allergen and, after its characterization. A 35-year-old nonatopic female with allergic episodes after ingestion of several types of meat was studied. Skin tests (prick and prick-to-prick); total and specific immunoglobulin E (IgE) determination; sodium dodecyl sulphate-polyacrylamide gel electrophoresis and specific IgE determination by immunoblotting under different conditions were performed. A 17-kDa allergen was semipurified by ethanol fractionation and its amino-terminal sequence was determined. The existence of specific IgE directed to this protein was studied by immunoblot in 80 atopic patients. The patient showed specific IgE antibodies to a 17-kDa protein. During the isolation of this allergen it was found that a 70-90% (vol/vol) ethanol concentration was able to purify the protein. The characterization revealed that it was a heat-resistant protein without disulfide bonds. N-terminal amino acid sequence (16 residues) showed identity with myoglobin. The study of specific IgE to this allergen among atopic patients showed that it was recognized by about 1% of the subjects. We describe a case of meat allergy caused by myoglobin. This is the first described case of monosensitization to this protein.
