title: A dual role for Mannan-binding lectin-associated serine protease 2 (MASP-2) in HIV infection.
abstract: Mannan-binding lectin (MBL) - associated serine protease 2 (MASP-2) co-activates the lectin pathway of complement in response to several viral infections. The quality of this response partly depends on MASP2 gene polymorphisms, which modulate MASP-2 function and serum levels. In this study we investigated a possible role of MASP2 polymorphisms, MASP-2 serum levels and MBL-mediated complement activation in the susceptibility to HIV/AIDS and HBV/HCV coinfection.
  
  
  
  A total of 178 HIV patients, 89 (50%) coinfected with HBV/HCV, 51.7% female, average age 40 (12-73) years, and 385 controls were evaluated. MASP-2 levels and MBL-driven complement activation were evaluated by enzyme-linked immunosorbent assay and 11 MASP2 polymorphisms from the promoter to the last exon were haplotyped using multiplex sequence-specific PCR.
  
  
  
  Genotype distribution was in Hardy-Weinberg equilibrium and differed between HIV+ patients and controls (P=0.030), irrespective of HBV or HCV coinfection. The p.126L variant, which was associated with MASP-2 levels <200ng/mL (OR=5.0 [95%CI=1.3-19.2] P=0.019), increased the susceptibility to HIV infection (OR=5.67 [95%CI=1.75-18.33], P=0.004) and to HIV+HBV+ status (OR=6.44 [95%CI=1.69-24.53, P=0.006). A similar association occurred with the ancient haplotype harboring this variant, AGCDV (OR=2.35 [95%CI=1.31-4.23], P=0.004). On the other hand, p.126L in addition to other variants associated with low MASP-2 levels-p.120G, p.377A and p.439H, presented a protective effect against AIDS (OR=0.25 [95%CI=0.08-0.80], P=0.020), independently of age, sex, hepatic function and viral load. MASP-2 serum levels were lower in HIV+ and HIV+HBV+ patients than in controls (P=0.0004). Among patients, MASP-2 levels were higher in patients with opportunistic diseases (P=0.001) and AIDS (P=0.004). MASP-2 levels correlated positively with MBL/MASP2-mediated C4 deposition (r=0.29, P=0.0002) and negatively with CD4+ cell counts (r=-0.21, P=0.018), being related to decreased CD4+ cell counts (OR=5.8 [95%CI=1.23-27.5, P=0.026).
  
  
  
  Genetically determined MASP-2 levels seem to have a two-edge effect in HIV and probably HCV/HBV coinfection, whereas low levels increase the susceptibility to infection, but on the other side protects against AIDS.
authors: Laboratório de Imunopatologia Molecular, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brazil; Laboratório de Genética Molecular Humana, Universidade Federal do Paraná, Curitiba, Brazil.
authors: Angelica Beate Winter
authors: AB
authors: Boldt
authors: Laboratório de Imunopatologia Molecular, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brazil.
authors: Márcia Holsbach
authors: MH
authors: Beltrame
authors: Laboratório de Imunopatologia Molecular, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brazil.
authors: Sandra Jeremias
authors: SJ
authors: Catarino
authors: Laboratório de Imunopatologia Molecular, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brazil.
authors: Caroline Grisbach
authors: CG
authors: Meissner
authors: Laboratório de Imunopatologia Molecular, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brazil.
authors: Regina
authors: R
authors: Tizzot
authors: Laboratório de Imunopatologia Molecular, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brazil. Electronic address: iarareason@hc.ufpr.br.
authors: Iara Jose
authors: IJ
authors: Messias-Reason
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D060085:Coinfection / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D015658:HIV Infections / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D006509:Hepatitis B / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D006526:Hepatitis C / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases
keywords: HCV/HBV coinfection; HIV; Haplotype-specific genotyping; MASP-2; MASP2 polymorphism