A dual role for Mannan-binding lectin-associated serine protease 2 (MASP-2) in HIV infection. (October 2016)

• Record Type: Journal Article
• Authors: Boldt, Angelica Beate Winter; Beltrame, Márcia Holsbach; Catarino, Sandra Jeremias; Meissner, Caroline Grisbach; Tizzot, Regina; Messias-Reason, Iara Jose
• Is Part Of: Molecular immunology. Volume 78(2016:Oct.)
• Page Start: 48
• Page End: 56
• Publication Date: 2016-10
• Subjects: HIV -- MASP2 polymorphism -- MASP-2 -- HCV/HBV coinfection -- Haplotype-specific genotyping; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2016.08.015
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: CDV haplotype and p.126L increase the susceptibility to HIV and HIV + HBV+ status. MASP2*1C2-l haplotype was associated with protection against AIDS. MASP-2 serum levels are lower in HIV patients than in controls. MASP-2 serum levels correlated positively with MBL-mediated C4 deposition. Abstract: Background: 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. Methods: 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. Results: 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 <200 ng/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). Conclusions: 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.