@article{95202,
  keywords = {Hepatitis B, complement 3b receptors, complement system proteins, ficolin, genetic polymorphisms, leprosy, mannose-binding lectin, mannose-binding protein-associated serine proteases},
  author = {Boldt A and Oliveira-Toré C and Kretzschmar GC and Mendes H and Stinghen ST and Andrade FA and Bumiller-Bini V and Gonçalves LB and Braga ACDM and Stahlke E and Velavan T and Thiel S and de Messias-Reason IJT},
  title = {Hepatitis B Virus Infection Among Leprosy Patients: A Case for Polymorphisms Compromising Activation of the Lectin Pathway and Complement Receptors.},
  abstract = {<p>Thousands of leprosy patients not only suffer from physical deformities, but also either have or have had hepatitis B virus (HBV) coinfection. Polymorphisms of the complement system modulate susceptibility to leprosy, but genetic susceptibility to past or present HBV infection is unknown. We used sequencing and multiplex sequence-specific PCR to genotype 72 polymorphisms of seven genes (, ) encoding components of the lectin pathway, and two genes encoding complement receptors () in 190 patients, of which 74 were positive for HBsAg and/or anti-HBc (HBV+, 93.2% with a resolved infection) and 116 lepromatous patients, and 408 HBV-blood donors. In addition, we tested for levels of proteins of the lectin pathway. We found no difference between serum concentrations of mannan-binding lectin (MBL), MBL-associated serine proteins (MASP-1, MASP-2, MASP-3, MAp44), ficolin-3 (FCN-3), soluble complement receptor 1 (sCR1) and MBL mediated C4 activation, measured by ELISA or TRIFMA in up to 167 HBV+ and HBV- patients. Haplotypes lowering protein levels or encoding dysfunctional proteins increased susceptibility to HBV infection:  (OR = 3.4, p = 0.02),  (OR = 4.0, p = 0.015) and  (OR = 5.4, p = 0.03). Conversely,  haplotype, associated with higher gene expression, was protective (OR = 0.56, P = 0.033). Other haplotypes associated with HBV susceptibility were:  (OR = 19.25, P = 0.003),  (OR = 2.65, P = 0.011) and  (OR = 12.55, P = 0.014). Some polymorphisms in ficolin genes associated with lower protein levels increased susceptibility to leprosy/HBV infection:  (OR = 1.66, P = 0.029),  (OR = 6.73, P = 0.008), and  (OR = 12.54, P = 0.037), and to lepromatous disease/HBV infection:  (OR = 2.5, P = 0.009), whereas  was associated with increased FCN-2 expression and resistance against coinfection (OR = 0.29, P = 0.026). These associations were independent of demographic factors and did not increase susceptibility to leprosy , except . Associations for , and  variants were also independent of each other. In conclusion, polymorphisms compromising activation of the lectin pathway of complement increase susceptibility to HBV infection, with ficolin polymorphisms playing a major role in modulating the susceptibility among leprosy patients.</p>},
  year = {2020},
  journal = {Frontiers in immunology},
  volume = {11},
  pages = {574457},
  month = {01/2020},
  issn = {1664-3224},
  url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904891/pdf/fimmu-11-574457.pdf},
  doi = {10.3389/fimmu.2020.574457},
  language = {eng},
}