Detrimental Effects of Mannose‐Binding Lectin<i>(MBL2)</i>Promoter Genotype<i>XA/XA</i>on HIV‐1 Vertical Transmission and AIDS Progression

Mangano, Andrea; Rocco, Carlos; Marino, Sara; Mecikovsky, Débora; Genre, Fernanda; Aulicino, Paula; Bologna, Rosa; Sen, Luisa

doi:10.1086/590498

Cited by 37 publications

(33 citation statements)

References 40 publications

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“…In contrast to our findings of no association between HIV disease progression and MBL deficiency, other studies showed a higher median plasma MBL concentration in patients who progressed to AIDS compared to those who did not, indicating a protective role of MBL deficiency (Mangano et al, 2008). In addition, in our study population plasma MBL concentration was not a predictor of HIV-1 status, CD4…”

Section: Discussioncontrasting

confidence: 99%

“…Mannose Binding Lectin (MBL), an important constituent of the innate immune system, has been widely investigated in different populations to determine association between MBL deficiency and susceptibility to several other infections (Antony et al, 2013;Hu et al, 2010;Zinyama-Gutsire et al, 2015) and the role of MBL deficiency in HIV disease progression (Boniotto et al, 2000;Catano et al, 2008;Hundt et al, 2000;Maas et al, 1998;Mangano et al, 2008;Prohaszka et al, 1997;Senaldi et al, 1995;Tan et al, 2009;Vallinoto et al, 2008) and survival Maas et al, 1998).…”

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confidence: 99%

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HIV-1 Disease Progression and Survival in an Adult Population in Zimbabwe: Is There an Effect of the Mannose Binding Lectin Deficiency?

Zinyama-Gutsire

Chasela

Kallestrup

et al. 2015

OMICS: A Journal of Integrative Biology

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HIV infection remains a major global health burden since its discovery in 1983. Sub-Saharan Africa is the region hardest hit by the HIV/AIDS pandemic where 63% of the 33 million infected people live. While there is marked person-to-person variability in susceptibility, progression, and survival with HIV infection, there is a paucity of predictive diagnostics associated with these clinical endpoints. In this regard, the deficiency in plasma Mannose Binding Lectin (MBL) is a common opsonic defect reported to increase susceptibility infections, including HIV. To the best of our knowledge, we report here the first study on the putative role of MBL deficiency on HIV progression and survival in an African adult population. We hypothesized that MBL deficiency has a role to play in HIV infection by increasing HIV disease progression and decreasing survival. We assessed the role of MBL deficiency on HIV disease progression and survival in a Zimbabwean adult population enrolled in the Mupfure Schistosomiasis and HIV (MUSH) cohort. We analyzed blood samples for MBL levels, MBL2 genotypes, HIV-1 status, viral load, and CD4 + T cell counts. Participants were followed for 3 years wherein the endpoints were measured at baseline, 6 weeks, and 3, 6, 12, 24, and 36 months. Disease progression was measured as the rate of decline in CD4 + T cell counts and the rate of increase in HIV viral load. We assessed 197 HIV positive adults where 83% (164) were women with a median age of 31 years. Prevalence of plasma MBL deficiency (less than 100 lg/L) and MBL2 deficient genetic variants (A/O and O/O genotypes) was 21% (42 out of 197) and 39% (74 out of 190), respectively. We did not observe a significant role to explain individual variation in mortality, change of CD4 + T cell count, and viral load by MBL plasma deficiency or MBL2 genetic variants from baseline to 3 years follow up period in this adult population. We suggest the need for global OMICS research and that the present findings attest to the large betweenpopulation variability in a host of factors that can predispose individuals susceptible to HIV progression and mortality. We therefore cannot recommend at this time the use of plasma MBL levels or MBL2 genetic variants as a prognostic marker in HIV infection, disease progression, and survival in this adult population in Africa.

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Section: Discussioncontrasting

confidence: 99%

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confidence: 99%

HIV-1 Disease Progression and Survival in an Adult Population in Zimbabwe: Is There an Effect of the Mannose Binding Lectin Deficiency?

Zinyama-Gutsire

Chasela

Kallestrup

et al. 2015

OMICS: A Journal of Integrative Biology

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“…This suggests a possible predisposition to HIV-1 infection due to the high frequency of HIV-infected subjects carrying the allele L in homozygous form, but no significant differences in the frequencies of alleles, haplotypes or genotypes among HIV-1-infected and uninfected subjects was reported. Nielsen et al (1995) and Pastinen et al (1998) have shown that HIV-1-infected subjects presented lower serum levels of MBL compared to uninfected subjects and, according to Mangano et al (2008), MBL plasma concentration is associated with the rate of AIDS progression when considering vertical transmission of the virus. This model was not supported by Senaldi et al (1999).…”

Section: Discussionmentioning

confidence: 99%

Characterization of polymorphisms in the mannose-binding lectin gene promoter among human immunodeficiency virus 1 infected subjects

Vallinoto

Muto

Alves

et al. 2008

Mem. Inst. Oswaldo Cruz

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“…Taking into account that S. pneumoniae is the leading cause of severe pneumonia in children, we can assume that the prevalence of HIV infection among cases included in our study would be remarkable. MBL-deficient genotypes have been shown to influence vertical transmission of HIV infection and AIDS progression, as well as AIDS progression among HIV-infected children [31]. HIV-infected individuals may have higher susceptibility to less invasive serotypes than other children.…”

Section: Paediatric Respiratory Infections X Vallès Et Almentioning

confidence: 99%

Serotype-specific pneumococcal disease may be influenced by mannose-binding lectin deficiency

Vallès¹,

Roca²,

Lozano³

et al. 2010

European Respiratory Journal

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Previous studies of the association between the mannose-binding lectin pathway deficiencies and invasive pneumococcal disease are inconclusive. Invasiveness of Streptococcus pneumoniae is dependent on serotype. We aimed to determine the association between invasive pneumococcal disease and MBL2 and MASP2 genetic variants, regarding serotype distribution.A hospital-based case-control study was conducted in children admitted to hospital in rural Mozambique in June 2002-November 2003. The study included children admitted to hospital with invasive pneumococcal disease, in whom S. pneumoniae was isolated from blood and subsequently serotyped. Sequence-based typing analysis of amplicons covering the polymorphic regions of MASP2 (exon 3) and MBL2 (promoter and exon 1) was performed.An overall high frequency of MBL2 genotypes associated with low serum levels of MBL (43%) was found. Carriers of MBL-deficient genotypes were associated with invasive pneumococcal disease produced by low-invasive serotypes (OR 5.55, p50.01).Our data suggest that susceptibility to pneumococcal disease among MBL-deficient patients may be influenced by serotype invasiveness. Type-specific capsular serotype of S. pneumoniae would need to be taken into account in further genetic association studies of invasive pneumococcal disease.

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Detrimental Effects of Mannose‐Binding Lectin(MBL2)Promoter GenotypeXA/XAon HIV‐1 Vertical Transmission and AIDS Progression

Abstract: Our results demonstrate that homozygosity for the MBL2 promoter genotype XA/XA is an important genetic determinant of HIV-1 acquisition through vertical transmission and the pathogenesis of pediatric HIV/AIDS, via a mechanism that remains to be established.

Cited by 37 publications

References 40 publications

HIV-1 Disease Progression and Survival in an Adult Population in Zimbabwe: Is There an Effect of the Mannose Binding Lectin Deficiency?

HIV-1 Disease Progression and Survival in an Adult Population in Zimbabwe: Is There an Effect of the Mannose Binding Lectin Deficiency?

Characterization of polymorphisms in the mannose-binding lectin gene promoter among human immunodeficiency virus 1 infected subjects

Serotype-specific pneumococcal disease may be influenced by mannose-binding lectin deficiency

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