Anti-α-Gal antibodies detected by novel neoglycoproteins as a diagnostic tool for Old World cutaneous leishmaniasis caused by<i>Leishmania major</i>

Subramaniam, Krishanthi; Austin, Victoria Macleod; Schocker, Nathaniel S.; Montoya, Alba L.; Anderson, Matthew; Ashmus, Roger A.; Mesri, Mina; Al-Salem, Waleed S.; Almeida, Igor C.; Michael, Katja; Acosta-Serrano, Álvaro

doi:10.1017/s0031182018000860

Cited by 8 publications

(13 citation statements)

References 30 publications

(37 reference statements)

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“…Our previous studies showed that the sera of OWCL patients from Saudi Arabia contain elevated levels of anti-α-Gal IgG antibodies 45 that partially recognize simple α-Gal-containing saccharides, but a specific α-Gal BMK remained elusive. 46 Therefore, we shifted our focus to α-galactopyranose- and β-galactofuranose-containing saccharides of the terminal, nonreducing glycan portions of type-2 GIPLs of L. major . The synthesis of a terminal trisaccharide of type-2 GIPLs and a heptasaccharide present in LPGs of Leishmania parasites has been reported.…”

Section: Resultsmentioning

confidence: 99%

“…In a more recent study, we assayed several other NGPs containing other α-Gal-glycotopes linked to BSA, including α-Gal p ( NGP3b ), Gal p α1,3Gal p α ( NGP17b ), Gal p α1,3Gal p β ( NGP9b ), Gal p α1,6[Gal p α1,2]Gal p β ( NGP11b ), and Gal p α1,3Gal p β1,4Glc p β ( NGP1b ). 46 When assayed by chemiluminescent ELISA with sera from L. major- infected patients with active CL lesion ( n = 17) or cured ( n = 29) or sera from heterologous diseases, the most promising diagnostic potential (AUC ROC = 0.8) was observed with NGP3b (α-Gal p –BSA). Although this AUC value is considered acceptable for a diagnostic test, a higher accuracy (AUC = 0.9–1.0), as we observed in most ROC curves in this study, is desirable.…”

Section: Resultsmentioning

confidence: 99%

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Reversed Immunoglycomics Identifies α-Galactosyl-Bearing Glycotopes Specific for Leishmania major Infection

Montoya

Austin

Portillo

et al. 2021

JACS Au

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All healthy humans have high levels of natural anti-α-galactosyl (α-Gal) antibodies (elicited by yet uncharacterized glycotopes), which may play important roles in immunoglycomics: (a) potential protection against certain parasitic and viral zoonotic infections; (b) targeting of α-Gal-engineered cancer cells; (c) aiding in tissue repair; and (d) serving as adjuvants in α-Gal-based vaccines. Patients with certain protozoan infections have specific anti-α-Gal antibodies, elicited against parasite-derived α-Gal-bearing glycotopes. These glycotopes, however, remain elusive except for the well-characterized glycotope Galα1,3Galβ1,4GlcNAcα, expressed by Trypanosoma cruzi . The discovery of new parasitic glycotopes is greatly hindered by the enormous structural diversity of cell-surface glycans and the technical challenges of classical immunoglycomics, a top-down approach from cultivated parasites to isolated glycans. Here, we demonstrate that reversed immunoglycomics, a bottom-up approach, can identify parasite species-specific α-Gal-bearing glycotopes by probing synthetic oligosaccharides on neoglycoproteins. This method was tested here seeking to identify as-yet unknown glycotopes specific for Leishmania major , the causative agent of Old-World cutaneous leishmaniasis (OWCL). Neoglycoproteins decorated with synthetic α-Gal-containing oligosaccharides derived from L. major glycoinositolphospholipids served as antigens in a chemiluminescent enzyme-linked immunosorbent assay using sera from OWCL patients and noninfected individuals. Receiver-operating characteristic analysis identified Gal p α1,3Gal f β and Gal p α1,3Gal f β1,3Man p α glycotopes as diagnostic biomarkers for L. major- caused OWCL, which can distinguish with 100% specificity from heterologous diseases and L. tropica- caused OWCL. These glycotopes could prove useful in the development of rapid α-Gal-based diagnostics and vaccines for OWCL. Furthermore, this method could help unravel cryptic α-Gal-glycotopes of other protozoan parasites and enterobacteria that elicit the natural human anti-α-Gal antibodies.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Reversed Immunoglycomics Identifies α-Galactosyl-Bearing Glycotopes Specific for Leishmania major Infection

Montoya

Austin

Portillo

et al. 2021

JACS Au

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“…Anti-Leishmania antibodies are barely detectable in CL and to some extent these can be detected in ML and DCL but with limited and variable performance [62]. New opportunities for the serological diagnosis of CL may be brought by the detection of anti-α-Gal antibodies, with promising preliminary results for Old World leishmaniasis, nevertheless this field requires further research [72].…”

Section: Unlike In Vl CL Is Not Characterized By An Elevated Productmentioning

confidence: 99%

Leishmaniasis immunopathology—impact on design and use of vaccines, diagnostics and drugs

et al. 2020

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Leishmaniasis is a disease complex caused by 20 species of protozoan parasites belonging to the genus Leishmania. In humans the it has two main clinical forms, visceral leishmaniasis (VL) and cutaneous or tegumentary leishmaniasis (CL), as well as several other cutaneous manifestations in a minority of cases. In the mammalian host Leishmania infect different populations of macrophages where they multiply and survive in the phagolysosomal compartment. The progression of both VL and CL depends on the maintenance of a parasite-specific immunosuppressive state based upon this host macrophage infection. The complexity and variation of immune responses and immunopathology in humans and the different host interactions of the different Leishmania species has an impact upon the effectiveness of vaccines, diagnostics and drugs. Powered by Edit orial Manager® and ProduXion Manager® from Aries Syst em s Corporat ion Leishmaniasis immunopathologyimpact on design and use of vaccines, diagnostics and drugs

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“…α-Gal immunity has been studied in other parasites, such as Leishmania major and Plasmodium falciparum . Neoglycoproteins containing α-Gal have been described as diagnostic tools for cutaneous leishmaniasis [ 110 ] and for protection against the parasite [ 111 , 112 ]. In Plasmodium falciparum , the agent of malaria, terminal α-linked galactosyl units, recognized by immune sera, are present in carbohydrate chains of glycoproteins [ 113 , 114 ].…”

Section: Structure Of Glycans In Mucins From Mammalian Cell-derivementioning

confidence: 99%

The Glycan Structure of T. cruzi mucins Depends on the Host. Insights on the Chameleonic Galactose

Giorgi

Lederkremer

2020

Molecules

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Trypanosoma cruzi, the protozoa that causes Chagas disease in humans, is transmitted by insects from the Reduviidae family. The parasite has developed the ability to change the structure of the surface molecules, depending on the host. Among them, the mucins are the most abundant glycoproteins. Structural studies have focused on the epimastigotes and metacyclic trypomastigotes that colonize the insect, and on the mammal trypomastigotes. The carbohydrate in the mucins fulfills crucial functions, the most important of which being the accepting of sialic acid from the host, a process catalyzed by the unique parasite trans-sialidase. The sialylation of the parasite influences the immune response on infection. The O-linked sugars have characteristics that differentiate them from human mucins. One of them is the linkage to the polypeptide chain by the hexosamine, GlcNAc, instead of GalNAc. The main monosaccharide in the mucins oligosaccharides is galactose, and this may be present in three configurations. Whereas β-d-galactopyranose (β-Galp) was found in the insect and the human stages of Trypanosoma cruzi, β-d-galactofuranose (β-Galf) is present only in the mucins of some strains of epimastigotes and α-d-galactopyranose (α-Galp) characterizes the mucins of the bloodstream trypomastigotes. The two last configurations confer high antigenic properties. In this review we discuss the different structures found and we pose the questions that still need investigation on the exchange of the configurations of galactose.

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Anti-α-Gal antibodies detected by novel neoglycoproteins as a diagnostic tool for Old World cutaneous leishmaniasis caused byLeishmania major

Cited by 8 publications

References 30 publications

Reversed Immunoglycomics Identifies α-Galactosyl-Bearing Glycotopes Specific for Leishmania major Infection

Reversed Immunoglycomics Identifies α-Galactosyl-Bearing Glycotopes Specific for Leishmania major Infection

Leishmaniasis immunopathology—impact on design and use of vaccines, diagnostics and drugs

The Glycan Structure of T. cruzi mucins Depends on the Host. Insights on the Chameleonic Galactose

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