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Hepatitis B Virus Infection Among Leprosy Patients: A Case for Polymorphisms Compromising Activation of the Lectin Pathway and Complement Receptors.

Abstract

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.

More information

Type
Journal Article
Author
Boldt A
Oliveira-Toré C
Kretzschmar GC
Mendes H
Stinghen ST
Andrade FA
Bumiller-Bini V
Gonçalves LB
Braga ACDM
Stahlke E
Velavan T
Thiel S
de Messias-Reason IJT