Molecular Immunology 78 (2016) 48–56 Contents lists available at ScienceDirect Molecular Immunology journal homepage: www.elsevier.com/locate/molimm A dual role for Mannan-binding lectin-associated serine protease 2 (MASP-2) in HIV infection Angelica Beate Winter Boldt a,b , Márcia Holsbach Beltrame a , Sandra Jeremias Catarino a , Caroline Grisbach Meissner a , Regina Tizzot a , Iara Jose Messias-Reason a,∗ a Laboratório de Imunopatologia Molecular, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brazil b Laboratório de Genética Molecular Humana, Universidade Federal do Paraná, Curitiba, Brazil a r t i c l e i n f o Article history: Received 21 April 2016 Received in revised form 22 August 2016 Accepted 23 August 2016 Keywords: HIV MASP2 polymorphism MASP-2 HCV/HBV coinfection Haplotype-specific genotyping a b s t r a c t 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 activa- tion 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 suscep- tibility 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. © 2016 Elsevier Ltd. All rights reserved. 1. Introduction Presently over 36.9 million of individuals worldwide are infected with the human immunodeficiency virus (HIV), being one ∗ Corresponding author at: Laboratório de Imunopatologia Molecular, Departa- mento de Patologia Médica, Servic ¸ o de Anatomia Patológica, Hospital de Clínicas, Universidade Federal do Paraná (UFPR), Rua General Carneiro, 181, CEP 80060-900 Curitiba, PR, Brazil. E-mail addresses: iarareason@hc.ufpr.br, iara.reason@hc.ufpr.br (I.J. Messias-Reason). of the greatest pandemics of modern times. Despite the advance in diagnosis and treatment and efforts of prevention, there were still two million new HIV infections and 1.2 million deaths in the year of 2014 (Joint United Nations Programme on HIV/AIDS—UNAIDS, 2015). Currently in Brazil, approximately 798 thousand individuals are suffering from HIV/AIDS, with an annual detection of 40.6 thou- sand over the past five years and a mortality rate of 5.7 per 100,000 inhabitants in 2014. The South and Southeast regions in the country present the highest incidence of HIV and AIDS in the general pop- ulation and within pregnant women and children under the age of 5 (CN-DST/AIDS, 2015). http://dx.doi.org/10.1016/j.molimm.2016.08.015 0161-5890/© 2016 Elsevier Ltd. All rights reserved.