Role of mannose-binding lectin deficiency in HIV-1 and schistosoma infections in a rural adult population in Zimbabwe

Rutendo B L Zinyama-Gutsire; Charles Chasela; Hans O Madsen; Simbarashe Rusakaniko; Per Kallestrup; Michael Christiansen; Exnevia Gomo; Henrik Ullum; Christian Erikstrup; Shungu Munyati; Edith N Kurewa; Babill Stray-Pedersen; Peter Garred; Takafira Mduluza

doi:10.1371/journal.pone.0122659

Role of mannose-binding lectin deficiency in HIV-1 and schistosoma infections in a rural adult population in Zimbabwe

PLoS One. 2015 Apr 1;10(4):e0122659. doi: 10.1371/journal.pone.0122659. eCollection 2015.

Affiliations

¹ Faculty of Health Sciences, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa; Medical Research Council of Zimbabwe, Ministry of Health and Child Welfare, Harare, Zimbabwe; Letten Research Foundation, Harare, Zimbabwe.
² Faculty of Health Sciences, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa.
³ Tissue typing Laboratory, Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark.
⁴ Letten Research Foundation, Harare, Zimbabwe; University of Zimbabwe, College of Health Sciences, Harare, Zimbabwe.
⁵ Centre for Global Health, Department of Public Health, Aarhus University, Aarhus, Denmark.
⁶ Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institute, Copenhagen, Denmark.
⁷ Department of Medical Laboratory Sciences, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe.
⁸ Biomedical Research and Training Institute, Harare, Zimbabwe.
⁹ Division of Women and Children, Rigshospitalet Oslo University Hospital and University of Oslo, Oslo, Norway, and Letten Research Foundation, Harare, Zimbabwe; University of Zimbabwe, College of Health Sciences, Harare, Zimbabwe.
¹⁰ Laboratory of Molecular Medicine, Department of Clinical Immunology, Copenhagen University, Rigshospitalet, Copenhagen, Denmark.
¹¹ University of Zimbabwe, Biochemistry Department, Harare, Zimbabwe, and Department of Laboratory Medicine and Medical Sciences, University of KwaZulu Natal, Durban, South Africa.

Abstract

Background: Polymorphism in the MBL2 gene lead to MBL deficiency, which has been shown to increase susceptibility to various bacterial, viral and parasitic infections. We assessed role of MBL deficiency in HIV-1 and schistosoma infections in Zimbabwean adults enrolled in the Mupfure Schistosomiasis and HIV Cohort (MUSH Cohort).

Methods: HIV-1, S. haematobium and S. mansoni infections were determined at baseline. Plasma MBL concentration was measured by ELISA and MBL2 genotypes determined by PCR. We calculated and compared the proportions of plasma MBL deficiency, MBL2 structural variant alleles B (codon 54A>G), C (codon 57A>G), and D (codon 52T>C) as well as MBL2 promoter variants -550(H/L), -221(X/Y) and +4(P/Q) between HIV-1 and schistosoma co-infection and control groups using Chi Square test.

Results: We assessed 379 adults, 80% females, median age (IQR) 30 (17-41) years. HIV-1, S. haematobium and S. mansoni prevalence were 26%, 43% and 18% respectively in the MUSH baseline survey. Median (IQR) plasma MBL concentration was 800μg/L (192-1936μg/L). Prevalence of plasma MBL deficiency was 18% with high frequency of the C (codon 57G>A) mutant allele (20%). There was no significant difference in median plasma MBL levels between HIV negative (912μg/L) and HIV positive (688μg/L), p = 0.066. However plasma MBL levels at the assay detection limit of 20μg/L were more frequent among the HIV-1 infected (p = 0.007). S. haematobium and S. mansoni infected participants had significantly higher MBL levels than uninfected. All MBL2 variants were not associated with HIV-1 infection but promoter variants LY and LL were significantly associated with S. haematobium infection.

Conclusion: Our data indicate high prevalence of MBL deficiency, no evidence of association between MBL deficiency and HIV-1 infection. However, lower plasma MBL levels were protective against both S. haematobium and S. mansoni infections and MBL2 promoter and variants LY and LL increased susceptibility to S. haematobium infection.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Coinfection / blood
Coinfection / epidemiology
Coinfection / genetics
Female
Gene Frequency
Genetic Association Studies
Genetic Predisposition to Disease
HIV Infections / blood
HIV Infections / epidemiology
HIV Infections / genetics*
HIV-1*
Humans
Male
Mannose-Binding Lectin / blood
Mannose-Binding Lectin / deficiency*
Mannose-Binding Lectin / genetics
Metabolism, Inborn Errors / blood
Metabolism, Inborn Errors / epidemiology
Metabolism, Inborn Errors / genetics*
Polymorphism, Single Nucleotide
Prevalence
Promoter Regions, Genetic
Rural Population
Schistosomiasis haematobia / blood
Schistosomiasis haematobia / epidemiology
Schistosomiasis haematobia / genetics*
Schistosomiasis mansoni / blood
Schistosomiasis mansoni / epidemiology
Schistosomiasis mansoni / genetics*
Young Adult
Zimbabwe / epidemiology

Substances

MBL2 protein, human
Mannose-Binding Lectin

Supplementary concepts

Mannose-Binding Protein Deficiency

Grants and funding

Funding was provided by the Research Foundation of the Capital Region of Denmark and the Sven Andersen Research Foundation (Peter Garred and Hans O. Madsen), UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) through a grant for R Zinyama-Gutsire, grant No A30670, the Essential National Health Research Fund of the Ministry of Health and Child Welfare of Zimbabwe (P355) and a study fellowship for RBL Zinyama-Gutsire from The Fogarty International Centre, National Institutes of Health (NIH-USA) through the International Clinical, Operational and Health Services and Training Award (ICOHRTA) Programme (2008–2010). Per Kallestrup received funding from the Danish AIDS Foundation (F01-18, F01-19), The Danish Embassy in Zimbabwe (2001), The DANIDA Health Programme in Zimbabwe (2001), The US Centres for Disease Control and Prevention Programme in Zimbabwe. The Letten Research Foundation, University of Oslo Norway/Zimbabwe Collaborative PMTCT BHAMC Programme special mention Professor Letten F. Saugstad. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. An abstract of the results of this study was accepted and presented in Durban at the 6th South Africa AIDS conference as a poster, 18–21 June 2013, funded by the SA AIDS conference, abstract number A2288739 and the Letten Research Foundation, University of Oslo Norway/Zimbabwe Collaborative PMTCT BHAMC Programme.