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

  • Krishanthi S. Subramaniam (a1), Victoria Austin (a1), Nathaniel S. Schocker (a2), Alba L. Montoya (a2), Matthew S. Anderson (a2), Roger A. Ashmus (a2), Mina Mesri (a1), Waleed Al-Salem (a3), Igor C. Almeida (a4), Katja Michael (a2) and Alvaro Acosta-Serrano (a1) (a5)...

Abstract

Outbreaks of Old World cutaneous leishmaniasis (CL) have significantly increased due to the conflicts in the Middle East, with most of the cases occurring in resource-limited areas such as refugee settlements. The standard methods of diagnosis include microscopy and parasite culture, which have several limitations. To address the growing need for a CL diagnostic that can be field applicable, we have identified five candidate neoglycoproteins (NGPs): Galα (NGP3B), Galα(1,3)Galα (NGP17B), Galα(1,3)Galβ (NGP9B), Galα(1,6)[Galα(1,2)]Galβ (NGP11B), and Galα(1,3)Galβ(1,4)Glcβ (NGP1B) that are differentially recognized in sera from individuals with Leishmania major infection as compared with sera from heterologous controls. These candidates contain terminal, non-reducing α-galactopyranosyl (α-Gal) residues, which are known potent immunogens to humans. Logistic regression models found that NGP3B retained the best diagnostic potential (area under the curve from receiver-operating characteristic curve = 0.8). Our data add to the growing body of work demonstrating the exploitability of the human anti-α-Gal response in CL diagnosis.

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Corresponding author

Author for correspondence: Alvaro Acosta-Serrano, E-mail: alvaro.acosta-serrano@lstmed.ac.uk

References

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Abuzaid, AA, Abdoon, AM, Aldahan, MA, Alzahrani, AG, Alhakeem, RF, Asiri, AM, Alzahrani, MH and Memish, ZA (2017) Cutaneous leishmaniasis in Saudi Arabia: a comprehensive overview. Vector Borne and Zoonotic Diseases 17. doi: 10.1089/vbz.2017.2119.
Almeida, IC, Milani, SR, Gorin, PA and Travassos, LR (1991) Complement-mediated lysis of Trypanosoma cruzi trypomastigotes by human anti-alpha-galactosyl antibodies. Journal of Immunology 146, 23942400.
Al-Salem, WS, Ferreira, DM, Dyer, NA, Alyamani, EJ, Balghonaim, SM, Al-Mehna, AY, Al-Zubiany, S, Ibrahim el, K, Al Shahrani, AM, Alkhuailed, H, Aldahan, MA, Al Jarallh, AM, Abdelhady, SS, Al-Zahrani, MH, Almeida, IC and Acosta-Serrano, A (2014) Detection of high levels of anti-alpha-galactosyl antibodies in sera of patients with Old World cutaneous leishmaniasis: a possible tool for diagnosis and biomarker for cure in an elimination setting. Parasitology 141, 18981903.
Al-Salem, WPD, Subramaniam, K, Haines, LR, Kelly-Hope, L, Molyneux, DH, Hay, S and Acosta-Serrano, A (2016) Cutaneous leishmaniasis and the conflict in Syria. Emerging Infectious Disease 22.
Anish, C, Martin, CE, Wahlbrink, A, Bogdan, C, Ntais, P, Antoniou, M and Seeberger, PH (2013) Immunogenicity and diagnostic potential of synthetic antigenic cell surface glycans of Leishmania. ACS Chemical Biology 8, 24122422.
Aronson, N, Herwaldt, BL, Libman, M, Pearson, R, Lopez-Velez, R, Weina, P, Carvalho, E, Ephros, M, Jeronimo, S and Magill, A (2017) Diagnosis and treatment of leishmaniasis: clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). American Journal of Tropical Medicine and Hygiene 96, 2445.
Ashmus, RA, Schocker, NS, Cordero-Mendoza, Y, Marques, AF, Monroy, EY, Pardo, A, Izquierdo, L, Gallego, M, Gascon, J, Almeida, IC and Michael, K (2013) Potential use of synthetic alpha-galactosyl-containing glycotopes of the parasite Trypanosoma cruzi as diagnostic antigens for Chagas disease. Organic and Biomolecular Chemistry 11, 55795583.
Ayatollahi, J, Fattahi Bafghi, A and Shahcheraghi, SH (2014) Rare variants of cutaneous leishmaniasis presenting as eczematous lesions. Medical Journal of the Islamic Republic of Iran 28, 71.
Bailey, F, Mondragon-Shem, K, Hotez, P, Ruiz-Postigo, JA, Al-Salem, W, Acosta-Serrano, A and Molyneux, DH (2017) A new perspective on cutaneous leishmaniasis-implications for global prevalence and burden of disease estimates. PLOS Neglected Tropical Diseases 11, e0005739.
Brekke, OH and Sandlie, I (2003) Therapeutic antibodies for human diseases at the Dawn of the twenty-first century. Nature Reviews Drug Discovery 2, 5262.
de Vries, HJ, Reedijk, SH and Schallig, HD (2015) Cutaneous leishmaniasis: recent developments in diagnosis and management. American Journal of Clinical Dermatology 16, 99109.
Galili, U (1993) Evolution and pathophysiology of the human natural anti-alpha-galactosyl IgG (anti-Gal) antibody. Springer Seminars in Immunopathology 15, 155171.
Galili, U (2005) The alpha-gal epitope and the anti-Gal antibody in xenotransplantation and in cancer immunotherapy. Immunology and Cell Biology 83, 674686.
Galili, U, Mandrell, RE, Hamadeh, RM, Shohet, SB and Griffiss, JM (1988) Interaction between human natural anti-alpha-galactosyl immunoglobulin G and bacteria of the human flora. Infection and Immunity 56, 17301737.
Grund, B and Sabin, C (2010) Analysis of biomarker data: logs, odds ratios, and receiver operating characteristic curves. Current Opinion in HIV and AIDS 5, 473479.
Houseman, BT, Gawalt, ES and Mrksich, M (2003) Maleimide-functionalized self-assembled monolayers for the preparation of peptide and carbohydrate biochips. Langmuir 19, 15221531.
Imamura, A, Kimura, A, Ando, H, Ishida, H and Kiso, M (2006) Extended applications of di-tert-butylsilylene-directed alpha-predominant galactosylation compatible with C2-participating groups toward the assembly of various glycosides. Chemistry 12, 88628870.
Iniguez, E, Schocker, NS, Subramaniam, K, Portillo, S, Montoya, AL, Al-Salem, WS, Torres, CL, Rodriguez, F, Moreira, OC, Acosta-Serrano, A, Michael, K, Almeida, IC and Maldonado, RA (2017) An alpha-Gal-containing neoglycoprotein-based vaccine partially protects against murine cutaneous leishmaniasis caused by Leishmania major. PLOS Neglected Tropical Diseases 11, e0006039.
Mangold, A, Lebherz, D, Papay, P, Liepert, J, Hlavin, G, Lichtenberger, C, Adami, A, Zimmermann, M, Klaus, D, Reinisch, W and Ankersmit, HJ (2011) Anti-Gal titers in healthy adults and inflammatory bowel disease patients. Transplantation Proceedings 43, 39643968.
McConville, MJ and Bacic, A (1989) A family of glycoinositol phospholipids from Leishmania major. Isolation, characterization, and antigenicity. Journal of Biological Chemistry 264, 757766.
McConville, MJ, Homans, SW, Thomas-Oates, JE, Dell, A and Bacic, A (1990) Structures of the glycoinositolphospholipids from Leishmania major. A family of novel galactofuranose-containing glycolipids. Journal of Biological Chemistry 265, 73857394.
Moura, APV, Santos, LCB, Brito, CRN, Valencia, E, Junqueira, C, Filho, AAP, Sant'Anna, MRV, Gontijo, NF, Bartholomeu, DC, Fujiwara, RT, Gazzinelli, RT, McKay, CS, Sanhueza, CA, Finn, MG and Marques, AF (2017) Virus-like particle display of the alpha-Gal carbohydrate for vaccination against leishmania infection. ACS Central Science 3, 10261031.
Odiwuor, SO, Saad, AA, De Doncker, S, Maes, I, Laurent, T, El Safi, S, Mbuchi, M, Buscher, P, Dujardin, JC and Van der Auwera, G (2011) Universal PCR assays for the differential detection of all Old World Leishmania species. European Journal of Clinical Microbiology and Infectious Diseases 30, 209218.
Peng, P, Linseis, M, Winter, RF and Schmidt, RR (2016) Regioselective acylation of diols and triols: the cyanide effect. Journal of the American Chemical Society 138, 60026009.
Pinazo, MJ, Posada Ede, J, Izquierdo, L, Tassies, D, Marques, AF, de Lazzari, E, Aldasoro, E, Munoz, J, Abras, A, Tebar, S, Gallego, M, de Almeida, IC, Reverter, JC and Gascon, J (2016) Altered hypercoagulability factors in patients with chronic chagas disease: potential biomarkers of therapeutic response. PLOS Neglected Tropical Diseases 10, e0004269.
Pourmohammadi, B, Motazedian, M, Hatam, G, Kalantari, M, Habibi, P and Sarkari, B (2010) Comparison of three methods for diagnosis of cutaneous leishmaniasis. Iranian Journal of Parasitology 5, 18.
Saab, J, Fedda, F, Khattab, R, Yahya, L, Loya, A, Satti, M, Kibbi, AG, Houreih, MA, Raslan, W, El-Sabban, M and Khalifeh, I (2012) Cutaneous leishmaniasis mimicking inflammatory and neoplastic processes: a clinical, histopathological and molecular study of 57 cases. Journal of Cutaneous Pathology 39, 251262.
Saroufim, M, Charafeddine, K, Issa, G, Khalifeh, H, Habib, RH, Berry, A, Ghosn, N, Rady, A and Khalifeh, I (2014) Ongoing epidemic of cutaneous leishmaniasis among Syrian refugees, Lebanon. Emerging Infectious Diseases 20, 17121715.
Schocker, NS, Portillo, S, Brito, CR, Marques, AF, Almeida, IC and Michael, K (2016) Synthesis of Galalpha(1,3)Galbeta(1,4)GlcNAcalpha-, Galbeta(1,4)GlcNAcalpha- and GlcNAc-containing neoglycoproteins and their immunological evaluation in the context of Chagas disease. Glycobiology 26, 3950.
Schocker, NS, Portillo, S, Ashmus, RA, Brito, CRN, Silva, IE, Cordero-Mendoza, Y, Marques, AF, Monroy, EY, Pardo, A, Izquierdo, I, Gallego, M, Gascon, J, Almeida, IC and Michael, K (2017) Probing for Trypanosoma cruzi cell surface glycobiomarkers for the diagnosis and follow-up of chemotherapy of Chagas disease. In Witczak, ZJaBR (ed.), Coupling and Decoupling of Diverse Molecular Units in Glycosciences. Berlin: Springer Verlag, pp. 195211.
Yilmaz, B, Portugal, S, Tran, TM, Gozzelino, R, Ramos, S, Gomes, J, Regalado, A, Cowan, PJ, d'Apice, AJ, Chong, AS, Doumbo, OK, Traore, B, Crompton, PD, Silveira, H and Soares, MP (2014) Gut microbiota elicits a protective immune response against malaria transmission. Cell 159, 12771289.

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