Jens Christian Jensenius

Adding MASP1 to the lectin pathway-Leprosy association puzzle: Hints from gene polymorphisms and protein levels

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Adding MASP1 to the lectin pathway-Leprosy association puzzle : Hints from gene polymorphisms and protein levels. / Weinschutz Mendes, Hellen; Boldt, Angelica Winter; Stahlke, Ewalda; Jensenius, Jens Christian; Thiel, Steffen; Messias-Reason, Iara J Taborda.

In: PLOS Neglected Tropical Diseases , Vol. 14, No. 4, e0007534, 04.2020.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Weinschutz Mendes, H, Boldt, AW, Stahlke, E, Jensenius, JC, Thiel, S & Messias-Reason, IJT 2020, 'Adding MASP1 to the lectin pathway-Leprosy association puzzle: Hints from gene polymorphisms and protein levels', PLOS Neglected Tropical Diseases , vol. 14, no. 4, e0007534. https://doi.org/10.1371/journal.pntd.0007534

APA

Weinschutz Mendes, H., Boldt, A. W., Stahlke, E., Jensenius, J. C., Thiel, S., & Messias-Reason, I. J. T. (2020). Adding MASP1 to the lectin pathway-Leprosy association puzzle: Hints from gene polymorphisms and protein levels. PLOS Neglected Tropical Diseases , 14(4), [e0007534]. https://doi.org/10.1371/journal.pntd.0007534

CBE

Weinschutz Mendes H, Boldt AW, Stahlke E, Jensenius JC, Thiel S, Messias-Reason IJT. 2020. Adding MASP1 to the lectin pathway-Leprosy association puzzle: Hints from gene polymorphisms and protein levels. PLOS Neglected Tropical Diseases . 14(4):Article e0007534. https://doi.org/10.1371/journal.pntd.0007534

MLA

Vancouver

Weinschutz Mendes H, Boldt AW, Stahlke E, Jensenius JC, Thiel S, Messias-Reason IJT. Adding MASP1 to the lectin pathway-Leprosy association puzzle: Hints from gene polymorphisms and protein levels. PLOS Neglected Tropical Diseases . 2020 Apr;14(4). e0007534. https://doi.org/10.1371/journal.pntd.0007534

Author

Weinschutz Mendes, Hellen ; Boldt, Angelica Winter ; Stahlke, Ewalda ; Jensenius, Jens Christian ; Thiel, Steffen ; Messias-Reason, Iara J Taborda. / Adding MASP1 to the lectin pathway-Leprosy association puzzle : Hints from gene polymorphisms and protein levels. In: PLOS Neglected Tropical Diseases . 2020 ; Vol. 14, No. 4.

Bibtex

@article{7708d5e60b954b0cbea5f3fdb025ad9e,
title = "Adding MASP1 to the lectin pathway-Leprosy association puzzle: Hints from gene polymorphisms and protein levels",
abstract = "BACKGROUND: Deposition of complement factors on Mycobacterium leprae may enhance phagocytosis. Such deposition may occur through the lectin pathway of complement. Three proteins of the lectin pathway are produced from the gene MASP1: Mannan-binding lectin-associated serine protease 1 (MASP-1) and MASP-3 and mannan-binding lectin-associated protein of 44 kDa (MAp44). Despite their obvious importance, the roles played by these proteins have never been investigated in leprosy disease.METHODOLOGY: We haplotyped five MASP1 polymorphisms by multiplex sequence-specific PCR (intronic rs7609662*G>A and rs13064994*C>T, exon 12 3'-untranslated rs72549262*C>G, rs1109452*C>T and rs850314*G>A) and measured MASP-1, MASP-3 and MAp44 serum levels in 196 leprosy patients (60%, lepromatous) and 193 controls.PRINCIPAL FINDINGS: Lower MASP-3 and MAp44 levels were observed in patients, compared with controls (P = 0.0002 and P<0.0001, respectively) and in lepromatous, compared with non-lepromatous patients (P = 0.008 and P = 0.002, respectively). Higher MASP-3 levels were present in controls carrying variants/haplotypes associated with leprosy resistance (rs13064994*T, rs1109452_rs850314*CG within GT_CCG and rs850314*A: OR = 0.5-0.6, Pcorr = 0.01-0.04). Controls with rs1109452*T, included in susceptibility haplotypes (GT_GTG/GT_CTG: OR = 2.0, Pcorr = 0.03), had higher MASP-1 and lower MASP-3 levels (P≤0.009). Those with GC_CCG, presented increasing susceptibility (OR = 1.7, Pcorr = 0.006) and higher MAp44 levels (P = 0.015). MASP-3 expression decreased in patients, compared with controls carrying rs1109452_rs850314*CA or CG (P≤0.02), which may rely on exon 12 CpG methylation and/or miR-2861/miR-3181 mRNA binding.CONCLUSION: Polymorphisms regulating MASP-3/MAp44 availability in serum modulate leprosy susceptibility, underlining the importance of lectin pathway regulation against pathogens that exploit phagocytosis to parasitize host macrophages.",
author = "{Weinschutz Mendes}, Hellen and Boldt, {Angelica Winter} and Ewalda Stahlke and Jensenius, {Jens Christian} and Steffen Thiel and Messias-Reason, {Iara J Taborda}",
year = "2020",
month = apr,
doi = "10.1371/journal.pntd.0007534",
language = "English",
volume = "14",
journal = "P L o S Neglected Tropical Diseases (Online)",
issn = "1935-2735",
publisher = "public library of science",
number = "4",

}

RIS

TY - JOUR

T1 - Adding MASP1 to the lectin pathway-Leprosy association puzzle

T2 - Hints from gene polymorphisms and protein levels

AU - Weinschutz Mendes, Hellen

AU - Boldt, Angelica Winter

AU - Stahlke, Ewalda

AU - Jensenius, Jens Christian

AU - Thiel, Steffen

AU - Messias-Reason, Iara J Taborda

PY - 2020/4

Y1 - 2020/4

N2 - BACKGROUND: Deposition of complement factors on Mycobacterium leprae may enhance phagocytosis. Such deposition may occur through the lectin pathway of complement. Three proteins of the lectin pathway are produced from the gene MASP1: Mannan-binding lectin-associated serine protease 1 (MASP-1) and MASP-3 and mannan-binding lectin-associated protein of 44 kDa (MAp44). Despite their obvious importance, the roles played by these proteins have never been investigated in leprosy disease.METHODOLOGY: We haplotyped five MASP1 polymorphisms by multiplex sequence-specific PCR (intronic rs7609662*G>A and rs13064994*C>T, exon 12 3'-untranslated rs72549262*C>G, rs1109452*C>T and rs850314*G>A) and measured MASP-1, MASP-3 and MAp44 serum levels in 196 leprosy patients (60%, lepromatous) and 193 controls.PRINCIPAL FINDINGS: Lower MASP-3 and MAp44 levels were observed in patients, compared with controls (P = 0.0002 and P<0.0001, respectively) and in lepromatous, compared with non-lepromatous patients (P = 0.008 and P = 0.002, respectively). Higher MASP-3 levels were present in controls carrying variants/haplotypes associated with leprosy resistance (rs13064994*T, rs1109452_rs850314*CG within GT_CCG and rs850314*A: OR = 0.5-0.6, Pcorr = 0.01-0.04). Controls with rs1109452*T, included in susceptibility haplotypes (GT_GTG/GT_CTG: OR = 2.0, Pcorr = 0.03), had higher MASP-1 and lower MASP-3 levels (P≤0.009). Those with GC_CCG, presented increasing susceptibility (OR = 1.7, Pcorr = 0.006) and higher MAp44 levels (P = 0.015). MASP-3 expression decreased in patients, compared with controls carrying rs1109452_rs850314*CA or CG (P≤0.02), which may rely on exon 12 CpG methylation and/or miR-2861/miR-3181 mRNA binding.CONCLUSION: Polymorphisms regulating MASP-3/MAp44 availability in serum modulate leprosy susceptibility, underlining the importance of lectin pathway regulation against pathogens that exploit phagocytosis to parasitize host macrophages.

AB - BACKGROUND: Deposition of complement factors on Mycobacterium leprae may enhance phagocytosis. Such deposition may occur through the lectin pathway of complement. Three proteins of the lectin pathway are produced from the gene MASP1: Mannan-binding lectin-associated serine protease 1 (MASP-1) and MASP-3 and mannan-binding lectin-associated protein of 44 kDa (MAp44). Despite their obvious importance, the roles played by these proteins have never been investigated in leprosy disease.METHODOLOGY: We haplotyped five MASP1 polymorphisms by multiplex sequence-specific PCR (intronic rs7609662*G>A and rs13064994*C>T, exon 12 3'-untranslated rs72549262*C>G, rs1109452*C>T and rs850314*G>A) and measured MASP-1, MASP-3 and MAp44 serum levels in 196 leprosy patients (60%, lepromatous) and 193 controls.PRINCIPAL FINDINGS: Lower MASP-3 and MAp44 levels were observed in patients, compared with controls (P = 0.0002 and P<0.0001, respectively) and in lepromatous, compared with non-lepromatous patients (P = 0.008 and P = 0.002, respectively). Higher MASP-3 levels were present in controls carrying variants/haplotypes associated with leprosy resistance (rs13064994*T, rs1109452_rs850314*CG within GT_CCG and rs850314*A: OR = 0.5-0.6, Pcorr = 0.01-0.04). Controls with rs1109452*T, included in susceptibility haplotypes (GT_GTG/GT_CTG: OR = 2.0, Pcorr = 0.03), had higher MASP-1 and lower MASP-3 levels (P≤0.009). Those with GC_CCG, presented increasing susceptibility (OR = 1.7, Pcorr = 0.006) and higher MAp44 levels (P = 0.015). MASP-3 expression decreased in patients, compared with controls carrying rs1109452_rs850314*CA or CG (P≤0.02), which may rely on exon 12 CpG methylation and/or miR-2861/miR-3181 mRNA binding.CONCLUSION: Polymorphisms regulating MASP-3/MAp44 availability in serum modulate leprosy susceptibility, underlining the importance of lectin pathway regulation against pathogens that exploit phagocytosis to parasitize host macrophages.

UR - http://www.scopus.com/inward/record.url?scp=85083622093&partnerID=8YFLogxK

U2 - 10.1371/journal.pntd.0007534

DO - 10.1371/journal.pntd.0007534

M3 - Journal article

C2 - 32240160

VL - 14

JO - P L o S Neglected Tropical Diseases (Online)

JF - P L o S Neglected Tropical Diseases (Online)

SN - 1935-2735

IS - 4

M1 - e0007534

ER -