Grecia M Marrón-Liñares1, Lucía Núñez1, María G Crespo-Leiro2, Eduardo Barge-Caballero2, Jorge Pombo3, María Jesús Paniagua-Martin2, Natalia Suarez-Fuentetaja1, Javier Cid4, Zulaika Grille-Cancela2, Javier Muñiz-Garcia1, Carmela D Tan5, E Rene Rodríguez5, José Manuel Vázquez-Rodríguez2, Manuel Hermida-Prieto6. 1. Grupo de investigación en Cardiología, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Servizo Galego de Saúde (SERGAS), Universidade da Coruña (UDC), A Coruña, Spain. 2. Servicio de Cardiología, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC)-Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), SERGAS, Universidade da Coruña (UDC), A Coruña, Spain. 3. Servicio de Anatomía Patológica, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, A Coruña, Spain. 4. Servicio de Inmunología, Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, A Coruña, Spain. 5. Department of Pathology, The Cleveland Clinic, Cleveland, Ohio. 6. Grupo de investigación en Cardiología, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Servizo Galego de Saúde (SERGAS), Universidade da Coruña (UDC), A Coruña, Spain. Electronic address: manuelhermidaprieto@gmail.com.
Abstract
BACKGROUND: Heart transplantation (HT) is a life-saving treatment for patients with end-stage heart failure. One of the main problems after HT is the humoral response termed antibody-mediated rejection (AMR). Complement activation plays a key role in AMR contributing to graft damage. The aim of this study was to analyze genetic variants in genes related to the complement pathways that could be associated with the development of AMR. METHODS: Analysis of 51 genes related to the complement pathway was performed by next-generation sequencing in 46 HT recipients, 23 with and 23 without AMR. Statistical analysis was performed with SNPstats and R. RESULTS: We identified 2 single nucleotide polymorphisms, 1 in the mannose-binding lectin 2 gene (p.Gly54Asp-MBL2) and 1 in the complement factor properdin gene (p.Asn428(p=)-CFP), that showed significant association with the absence and development of AMR, respectively. Moreover, the presence of the rare allele in p.Gly54Asp-MBL2 control patients correlated with an immunodeficiency of mannose-binding lectin (6.24 ng/ml vs 207.50 ng/ml, p < 0.01), whereas the presence of the rare allele p.Asn428(p=)-CFP in patients with AMR correlated with higher levels of properdin protein (14.65 μg/ml vs 10.77 μg/ml, p < 0.05). CONCLUSIONS: AMR is a complex phenotype affected by many recipient factors. Variants in p.Gly54Asp-MBL2 and p.Asn428(p=)-CFP genes, encoding mannose-binding lectin 2 and properdin, may influence the risk of AMR.
BACKGROUND: Heart transplantation (HT) is a life-saving treatment for patients with end-stage heart failure. One of the main problems after HT is the humoral response termed antibody-mediated rejection (AMR). Complement activation plays a key role in AMR contributing to graft damage. The aim of this study was to analyze genetic variants in genes related to the complement pathways that could be associated with the development of AMR. METHODS: Analysis of 51 genes related to the complement pathway was performed by next-generation sequencing in 46 HT recipients, 23 with and 23 without AMR. Statistical analysis was performed with SNPstats and R. RESULTS: We identified 2 single nucleotide polymorphisms, 1 in the mannose-binding lectin 2 gene (p.Gly54Asp-MBL2) and 1 in the complement factor properdin gene (p.Asn428(p=)-CFP), that showed significant association with the absence and development of AMR, respectively. Moreover, the presence of the rare allele in p.Gly54Asp-MBL2 control patients correlated with an immunodeficiency of mannose-binding lectin (6.24 ng/ml vs 207.50 ng/ml, p < 0.01), whereas the presence of the rare allele p.Asn428(p=)-CFP in patients with AMR correlated with higher levels of properdin protein (14.65 μg/ml vs 10.77 μg/ml, p < 0.05). CONCLUSIONS: AMR is a complex phenotype affected by many recipient factors. Variants in p.Gly54Asp-MBL2 and p.Asn428(p=)-CFP genes, encoding mannose-binding lectin 2 and properdin, may influence the risk of AMR.
Authors: Marloes A H M Michels; Elena B Volokhina; Nicole C A J van de Kar; Lambertus P W J van den Heuvel Journal: Pediatr Nephrol Date: 2018-08-23 Impact factor: 3.714
Authors: P Piñon-Esteban; L Núñez; R Moure; G M Marrón-Liñares; X Flores-Rios; G Aldama-Lopez; J Salgado-Fernandez; R Calviño-Santos; F Rebollal-Leal; R Pan-Lizcano; N Vazquez-Gonzalez; G Bou; M Tomás; M Hermida-Prieto; J M Vazquez-Rodriguez Journal: Sci Rep Date: 2020-10-01 Impact factor: 4.379