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The genetically determined production of the alarmin eosinophil-derived neurotoxin is reduced in visceral leishmaniasis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Alribat Univ Hosp, Dept Clin Pathol & Microbiol, Khartoum, Sudan.ORCID iD: 0000-0001-8038-0397
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.ORCID iD: 0000-0003-1186-3226
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2018 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 126, no 1, p. 85-91Article in journal (Refereed) Published
Abstract [en]

Visceral leishmaniasis (VL) is the most severe form of leishmaniasis. Recent findings indicate that dendritic cells have a key role in the defense against the Leishmania parasite and that the activity of this cell may be modified by the eosinophil secretory protein eosinophil-derived neurotoxin (EDN). We hypothesized that the interactions between dendritic cells and EDN might be of importance in the disease development. Cellular content of EDN was analyzed by ELISA. The single-nucleotide polymorphisms at positions 405, 416, and 1122 in the EDN gene were analyzed by real-time PCR with TaqMan((R)) reagents. The study cohorts comprised 239 Sudanese subjects (65 healthy controls and 174 with VL) and 300 healthy Swedish controls. The eosinophil content of EDN was lower in VL as compared with controls (p < 0.0001). The EDN405 (G>C) genotype distribution was similar among Swedish and Sudanese controls, whereas VL subjects had a higher prevalence of the EDN405-GG genotype (p < 0.0001). The content of EDN in the eosinophils was closely linked to the EDN405 polymorphism (p = 0.0002). Our findings suggest that the predisposition to acquire VL is related to the genetic polymorphism of the EDN gene and the reduced production by the eosinophil of this gene product.

Place, publisher, year, edition, pages
WILEY , 2018. Vol. 126, no 1, p. 85-91
Keywords [en]
Visceral leishmaniasis, kala-azar, eosinophil granulocyte, polymorphism, RNASE2
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-338960DOI: 10.1111/apm.12780ISI: 000418846700011PubMedID: 29193305OAI: oai:DiVA.org:uu-338960DiVA, id: diva2:1175676
Available from: 2018-01-18 Created: 2018-01-18 Last updated: 2018-02-27Bibliographically approved

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Blom, KristinElShafie, Amir IbrahimJönsson, Ulla-BrittRönnelid, JohanHåkansson, LenaVenge, Per

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