Article

Association between mannose-binding lectin and HIV infection and progression in a Chinese population.

Division of Serum, National Institute for the Control of Pharmaceutical and Biological Products, Beijing, China.
Molecular Immunology (Impact Factor: 2.65). 09/2009; 47(2-3):632-8. DOI: 10.1016/j.molimm.2009.08.020
Source: PubMed

ABSTRACT Mannose-binding lectin (MBL) is a circulating pattern recognition molecule involved in the innate immune system that mediates phagocytosis and activates complement by binding to a carbohydrate extremity. Some MBL genetic polymorphisms result in deficient protein levels and increased susceptibility to infection. The objective of this study was to investigate the association between MBL2 exon 1 polymorphisms, serum levels of normal MBL, and HIV-1 infection and progression in a Chinese population. A total of 1075 adult patients infected with HIV-1 (532 male and 543 female) were recruited. The genotype of 145 patients was determined and the genotype frequencies compared with healthy population controls. The disease status of patients was evaluated for different MBL2 genotypes and normal MBL serum levels. MBL2 exon 1 polymorphisms (A/O or O/O) were significantly more common in HIV-1-infected patients than in the healthy controls. Patients in clinical categories B/C with severe diseases were significantly more likely to have one variant allele. There was a statistical relationship between MBL2 genotypes and MBL serum levels. In addition, higher CD4(+) T cell counts and ratios of CD4(+) T cells:CD8(+) T cells were observed in patients with medium MBL levels than with low or high MBL levels. Patients with mild diseases were also more likely to have medium MBL levels than high levels. Analysis of MBL levels with respect to sex yielded differences. Median MBL levels were substantially higher in males than in females in HIV-1-infected patients. Lower CD4(+) T cell counts were detected in males with low MBL levels, but the opposite was observed in females. Our results suggest that genetic polymorphisms resulting in MBL deficiency are associated with increased susceptibility to HIV-1 infection and disease progression in the studied population. Moreover, serum circulating levels of normal MBL in HIV-1-infected patients could be an important auxiliary biological marker in association with CD4(+) T cell counts in the evaluation of HIV-1 disease progression. The sex differences in the regulation of MBL serum levels during infection merit further exploration.

0 Bookmarks
 · 
94 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The high morbi-mortality associated with invasive candidiasis (IC) is a persistent problem in hospitals. Mannose-binding lectin (MBL) plays a role in innate immunity through its interaction with mannosylated molecules of Candida albicans. A correlation between MBL deficiency and vulvovaginal candidiasis or peritonitis has been reported. We investigated circulating MBL levels and their evolution during the course of IC. Sixty-eight patients with proven IC, 82 hospitalized patients (HP) without evidence of infection, and 70 healthy subjects (HS) were studied in order to examine the relationship between serum MBL and IC. Serum MBL levels were measured by enzyme-linked immunosorbent assay (ELISA). MBL levels were significantly higher in IC patients than in HP and HS (p < 0.0001, p < 0.0055, respectively). A change in MBL concentrations was observed during the course of IC, with a dramatic decrease during the 2 days before positive blood culture sampling. This decrease was concomitant with the presence of high levels of circulating mannan (Mn). Like MBL levels, anti-mannan antibodies (AMn) increased after the mannanemia/blood culture period. These findings suggest a possible role of MBL during the early stage of IC. The mechanisms that regulate these observations in terms of effect and consequences on innate and adaptive immunity and the prognosis of IC require further investigation.
    Journal of Clinical Immunology 07/2012; · 3.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mannose-binding lectin (MBL) plays an important role in immunity to HIV-1 infection. The exon1 coding polymorphisms of the MBL2 gene have been implicated in the susceptibility to HIV-1 infection, but the results were controversial. In the present study, a case-control study in a Chinese population was conducted to replicate the association, and then a meta-analysis combing our new data and published data was performed to clarify these findings. In total, 15 studies consisting 2219 HIV-1 patients and 2744 controls were included. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were assessed in the main analyses. By dividing the controls into two groups, healthy controls and HIV-1 exposed but seronegative (HESN) controls, we explored different genetic models and allelic model to detect the association. By using the healthy controls, we found that the MBL2 exon 1 polymorphisms were associated with hosts' susceptibility to HIV-1 infection in dominant model (p=0.01, 95% CI 1.05-1.43), recessive model (p<0.0001, 95% CI 1.35-2.28), allelic model (p<0.0001, 95% CI 1.12-1.37) and O/O vs. A/A model (p<0.00001, 95% CI 1.40-2.38). In the subgroup analysis by ethnicity, significant elevated risks were found in Caucasians (recessive model: p<0.0001, 95% CI 1.36-2.51), but not in Asians (recessive model: p=0.10, 95% CI 0.91-2.77). Collectively, our findings from our case-control replication study and meta-analysis suggested that the MBL2 gene exon 1 coding variants were associated with hosts' susceptibility to HIV-1 infection, especially in Caucasians, but not in Asians.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 09/2013; · 3.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The various neurological complications associated with HIV-1 infection, specifically HIV-associated neurocognitive disorders (HAND) persist as a major public health burden worldwide. Despite the widespread use of anti-retroviral therapy, the prevalence of HAND is significantly high. HAND results from the direct effects of an HIV-1 infection as well as secondary effects of HIV-1-induced immune reaction and inflammatory response. Complement, a critical mediator of innate and acquired immunity, plays important roles in defeating many viral infections by the formation of a lytic pore or indirectly by opsonization and recruitment of phagocytes. While the role of complement in the pathogenesis of HIV-1 infection and HAND has been previously recognized for over 15 years, it has been largely underestimated thus far. Complement can be activated through HIV-1 envelope proteins, mannose-binding lectins (MBL), and anti-HIV-1 antibodies. Complement not only fights against HIV-1 infection but also enhances HIV-1 infection. In addition, HIV-1 can hijack complement regulators such as CD59 and CD55 and can utilize these regulators and factor H to escape from complement attack. Normally, complement levels in brain are much lower than plasma levels and there is no or little complement deposition in brain cells. Interestingly, local production and deposition of complement are dramatically increased in HIV-1-infected brain, indicating that complement may contribute to the pathogenesis of HAND. Here, we review the current understanding of the role of complement in HIV-1 infection and HAND, as well as potential therapeutic approaches targeting the complement system for the treatment and eradications of HIV-1 infection.
    Journal of NeuroVirology 03/2014; · 2.85 Impact Factor