Identification of Babesia microti immunoreactive antigens by phage display cDNA screen.

Human babesiosis is a malaria-like illness caused by protozoan parasites of the genus Babesia. Babesia microti is responsible for most cases of human babesiosis in the United States, particularly in the Northeast and the Upper Midwest. Babesia microti is primarily transmitted to humans through the bite of infected deer ticks but also through the transfusion of blood components, particularly red blood cells. There is a high risk of severe and even fatal disease in immunocompromised patients. To date, serology testing relies on an indirect immunofluorescence assay that uses the whole Babesia microti antigen. Here, we report the construction of phage display cDNA libraries from Babesia microti-infected erythrocytes as well as human reticulocytes obtained from donors with hereditary hemochromatosis. Plasma samples were obtained from patients who were or had been infected with Babesia microti. The non-specific antibody reactivity of these plasma samples was minimized by pre-exposure to the human reticulocyte library. Using this novel experimental strategy, immunoreactive segments were identified in three Babesia microti antigens termed BmSA1 (also called BMN1-9; BmGPI12), BMN1-20 (BMN1-17; Bm32), and BM4.12 (N1-15). Moreover, our findings indicate that the major immunoreactive segment of BmSA1 does not overlap with the segment that mediates BmSA1 binding to mature erythrocytes. When used in combination, the three immunoreactive segments form the basis of a sensitive and comprehensive diagnostic immunoassay for human babesiosis, with implications for vaccine development.

Plasmodium falciparum Glutamic Acid-Rich Protein-Independent Polyclonal Antibodies Inhibit Malaria Parasite Growth in Human Erythrocytes.

Plasmodium falciparum glutamic acid-rich protein (PfGARP) is a recently characterized cell surface antigen encoded by Plasmodium falciparum, the causative agent of severe human malaria pathophysiology. Previously, we reported that the human erythrocyte band 3 (SLC4A1) serves as a host receptor for PfGARP. Antibodies against PfGARP did not affect parasite invasion and growth. We surmised that PfGARP may play a role in the rosetting and adhesion of malaria. Another study reported that antibodies targeting PfGARP exhibit potent inhibition of parasite growth. This inhibition occurred without the presence of any immune or complement components, suggesting the activation of an inherent density-dependent regulatory system. Here, we used polyclonal antibodies against PfGARP and a monoclonal antibody mAb7899 to demonstrate that anti-PfGARP polyclonal antibodies, but not mAb7899, exerted potent inhibition of parasite growth in infected erythrocytes independent of PfGARP. These findings suggest that an unknown malaria protein(s) is the target of growth arrest by polyclonal antibodies raised against PfGARP.

Differences in characteristics of US hematopoietic stem cell transplantation centers by proportion of racial or ethnic minorities.

Racial or ethnic minorities with leukemia who receive HLA-identical sibling hematopoietic stem cell transplants (HSCTs) are reported to have worse survival when compared with whites. Characteristics of US HSCT centers according to the proportion of ethnic minorities who undergo transplantation were compared to explore systematic differences among centers; the association with 100-day mortality was evaluated to determine whether center factors may explain the observed discrepant survival among ethnic minorities. One hundred sixteen US transplantation centers that performed HLA-identical sibling transplantations for leukemia were analyzed. We compared physician and health care provider staffing, transplantation unit procedure and resources, and medical center organization according to the volume procedure ratio of ethnic minorities who underwent transplantation and also according to the ratio of Hispanics who underwent transplantation. Centers that performed transplantation in a higher proportion of ethnic minorities were more likely to perform fewer transplantations per year, to have fewer devoted transplant beds, to be in an urban setting, to have a lower physician to patient volume ratio, and to follow up survivors 1 year after transplantation. Centers that performed transplantation in a higher proportion of Hispanics were more likely to perform fewer transplantations per year and to have fewer devoted transplantation beds, were less likely to perform outpatient transplantations, were more likely to be in an urban setting, and were less likely to have posttransplantation immunization protocols. Observed differences in center factors were not associated with 100-day mortality after adjustment for disease severity. Our results suggest that the inferior survival reported in ethnic minorities after HSCT may not be readily explained by center effects.