Multiplex Assay Detection of Immunoglobulin G Antibodies That Recognize Babesia microti Antigens

Priest, Jeffrey W.; Moss, Delynn M.; Won, Kimberly Y.; Todd, Charles W.; Henderson, Leslie; Jones, Cara C.; Wilson, Marianna

doi:10.1128/cvi.00313-12

Cited by 21 publications

(18 citation statements)

References 57 publications

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“…S5, available as supporting information in the online version of this paper). BmSA1 was used in a multiplex assay to detect B. microti IgG antibodies and showed specificity and sensitivity levels similar to those reported in this study for BmGPI12 . Our studies revealed that B. microti expresses a smaller set of GPI‐anchored proteins than that of P. falciparum .…”

Section: Discussionsupporting

confidence: 79%

“…BmSA1 was used in a multiplex assay to detect B. microti IgG antibodies and showed specificity and sensitivity levels similar to those reported in this study for BmGPI12. 10,38,41,61 Our studies revealed that B. microti expresses a smaller set of GPI-anchored proteins than that of P. falciparum. 21 The predicted GPI-anchored proteins of B. microti expressed in the blood stage of the parasite are different from those of P. falciparum and Toxoplasma gondii parasites.…”

Section: Discussionmentioning

confidence: 67%

“…1 Confirmation of recent or past babesiosis infection depends on laboratory diagnosis. Although different assays have been used to detect current and past infections of B. microti, [6][7][8][9][10][11] the indirect immunofluorescence assay (IFA) remains the most widely used antibody assay for determining exposure to B. microti. However, this assay is subjective and labor-intensive, requires highly trained personnel, and lacks the sensitivity and specificity necessary for optimal screening of the blood supply to prevent transfusion-transmitted babesiosis.…”

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confidence: 99%

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A targeted immunomic approach identifies diagnostic antigens in the human pathogen Babesia microti

et al. 2016

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BACKGROUND Babesia microti is a protozoan parasite responsible for the majority of reported cases of human babesiosis and a major risk to the blood supply. Laboratory screening of blood donors may help prevent transfusion-transmitted babesiosis but there is no Food and Drug Administration–approved screening method yet available. Development of a sensitive, specific, and highly automated B. microti antibody assay for diagnosis of acute babesiosis and blood screening could have an important impact on decreasing the health burden of B. microti infection. STUDY DESIGN AND METHODS Herein, we take advantage of recent advances in B. microti genomic analyses, field surveys of the reservoir host, and human studies in endemic areas to apply a targeted immunomic approach to the discovery of B. microti antigens that serve as signatures of active or past babesiosis infections. Of 19 glycosylphosphatidylinositol (GPI)-anchored protein candidates (BmGPI1-19) identified in the B. microti proteome, 17 were successfully expressed, printed on a microarray chip, and used to screen sera from uninfected and B. microti–infected mice and humans to determine immune responses that are associated with active and past infection. RESULTS Antibody responses to various B. microti BmGPI antigens were detected and BmGPI12 was identified as the best biomarker of infection that provided high sensitivity and specificity when used in a microarray antibody assay. CONCLUSION BmGPI12 alone or in combination with other BmGPI proteins is a promising candidate biomarker for detection of B. microti antibodies that might be useful in blood screening to prevent transfusion-transmitted babesiosis.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 67%

mentioning

confidence: 99%

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A targeted immunomic approach identifies diagnostic antigens in the human pathogen Babesia microti

et al. 2016

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“…20 In brief, the EIA uses four peptide antigens derived from two members of the BMN1 gene family, BMN1-9 (also termed BmSA1) and BMN1-17, which have been shown to be immunodominant in prior studies. 21-23 The four peptide antigens were identified by screening candidate peptides against a library of sera from patients with clinically diagnosed babesiosis as well as healthy controls. The biotinylated peptides were immobilized on streptavidin-coated microplates (Fig.…”

Section: Methodsmentioning

confidence: 99%

Serologic screening of United States blood donors for Babesia microti using an investigational enzyme immunoassay

Levin

Williamson²,

Bloch

et al. 2016

Transfusion

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BACKGROUND The tick-borne pathogen Babesia microti has become recognized as the leading infectious risk associated with blood transfusion in the United States, yet no Food and Drug Administration–licensed screening tests are currently available to mitigate this risk. The aim of this study was to evaluate the performance of an investigational enzyme immunoassay (EIA) for B. microti as a screening test applied to endemic and nonendemic blood donor populations. STUDY DESIGN AND METHODS The study aimed to test 20,000 blood donors from areas of the United States considered endemic for B. microti and 10,000 donors from a nonendemic area with the investigational B. microti EIA. Repeat-reactive samples were retested by polymerase chain reaction (PCR), blood smear, immunofluorescent assay (IFA), and immunoblot assay. In parallel, serum samples from symptomatic patients with confirmed babesiosis were tested by EIA, IFA, and immunoblot assays. RESULTS A total of 38 of 13,757 (0.28%) of the donors from New York, 7 of 4583 (0.15%) from Minnesota, and 11 of 8363 (0.13%) from New Mexico were found repeat reactive by EIA. Nine of the 56 EIA repeat-reactive donors (eight from New York and one from Minnesota) were positive by PCR. The specificity of the assay in a nonendemic population was 99.93%. Among IFA-positive clinical babesiosis patients, the sensitivity of the assay was 91.1%. CONCLUSION The B. microti EIA detected PCR-positive, potentially infectious blood donors in an endemic population and exhibited high specificity among uninfected and unexposed individuals. The EIA promises to provide an effective tool for blood donor screening for B. microti in a format amenable to high-throughput and cost-effective screening.

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“…IgG4 plays a role in both diseases, although that role is yet undefined. The monoclonal anti-IgG4 (clone HP6025; Zymed) antibodies verified to test for Babesiosis, imply that IgG4 is indeed present and in Babesiosis [19]. IgG4 levels have also been used to track responsiveness of RPF IgG4 related disease during treatment courses of rituximab and have been found to be a prognosticating factor [13].…”

Section: Discussionmentioning

confidence: 99%

Tics and Tumors, A Case Report of Babesiosis and IgG4 Retroperitoneal Fibrosis

Mannuel¹,

Adashek²,

Burley³

2019

ACO

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Retroperitoneal fibrosis (RPF) is a rare fibroinflammatory tumor of the retroperitoneum thought to be due to either idiopathic disease or related to underlying malignancy. Recently idiopathic RPF has been reclassified as an immune mediated IgG-4 related disease. When left unchecked, RPF often progresses, leading to compression of retroperitoneal structures and complete ureteral obstruction. Babesiosis is an intraerythrocytic parasitic disease that has demonstrated an in vitro association with increased IgG-4 levels. Both diseases are insidious, presenting with symptoms commonly identified as a viral prodrome, including malaise and fatigue. Within we present a case of a 68-year-old African American farmer with recent tick exposure who presented with symptoms of malaise, weight loss, elevated creatinine and new retroperitoneal mass. Serum testing revealed recent Babesiosis exposure, and biopsy revealed new onset retroperitoneal fibrosis. Once treated for babesiosis, the patient’s disease ceased its progression, and he remains on treatment with tamoxifen and stable disease. Further research of the in vivo association of babesiosis and IgG-4 related disease is needed.

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Multiplex Assay Detection of Immunoglobulin G Antibodies That Recognize Babesia microti Antigens

Cited by 21 publications

References 57 publications

A targeted immunomic approach identifies diagnostic antigens in the human pathogen Babesia microti

A targeted immunomic approach identifies diagnostic antigens in the human pathogen Babesia microti

Serologic screening of United States blood donors for Babesia microti using an investigational enzyme immunoassay

Tics and Tumors, A Case Report of Babesiosis and IgG4 Retroperitoneal Fibrosis

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