title: Polymorphisms in the lectin pathway of complement activation influence the incidence of acute rejection and graft outcome after kidney transplantation.
abstract: There are conflicting data on the role of the lectin pathway of complement activation and its recognition molecules in acute rejection and outcome after transplantation. To help resolve this we analyzed polymorphisms and serum levels of lectin pathway components in 710 consecutive kidney transplant recipients enrolled in the nationwide Swiss Transplant Cohort Study, together with all biopsy-proven rejection episodes and 1-year graft and patient survival. Functional mannose-binding lectin (MBL) levels were determined in serum samples, and previously described MBL2, ficolin 2, and MBL-associated serine protease 2 polymorphisms were genotyped. Low MBL serum levels and deficient MBL2 diplotypes were associated with a higher incidence of acute cellular rejection during the first year, in particular in recipients of deceased-donor kidneys. This association remained significant (hazard ratio 1.75, 95% confidence interval 1.18-2.60) in a Cox regression model after adjustment for relevant covariates. In contrast, there was no significant association with rates of antibody-mediated rejection, patient death, early graft dysfunction or loss. Thus, results in a prospective multicenter contemporary cohort suggest that MBL2 polymorphisms result in low MBL serum levels and are associated with acute cellular rejection after kidney transplantation. Since MBL deficiency is a relatively frequent trait in the normal population, our findings may lead to individual risk stratification and customized immunosuppression.
authors.affiliation: Transplantation Center, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; Transplantation Immunopathology Laboratory, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland. Electronic address: dela.golshayan@chuv.ch.
authors.forename: Déla
authors.initials: D
authors.lastname: Golshayan
authors.affiliation: Service of Infectious Diseases, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wójtowicz
authors.affiliation: Service of Infectious Diseases, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bibert
authors.affiliation: Service of Infectious Diseases, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Nitisha
authors.initials: N
authors.lastname: Pyndiah
authors.affiliation: Transplantation Center, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; Service of Infectious Diseases, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Oriol
authors.initials: O
authors.lastname: Manuel
authors.affiliation: Nephrologie und Transplantationsmedizin, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Binet
authors.affiliation: Centre Universitaire Romand de Transplantation, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
authors.forename: Leo H
authors.initials: LH
authors.lastname: Buhler
authors.affiliation: Department of Nephrology and Hypertension, Inselspital Bern, Bern, Switzerland.
authors.forename: Uyen
authors.initials: U
authors.lastname: Huynh-Do
authors.affiliation: Department of Nephrology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mueller
authors.affiliation: Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
authors.forename: Jürg
authors.initials: J
authors.lastname: Steiger
authors.affiliation: Transplantation Center, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; Transplantation Immunopathology Laboratory, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Manuel
authors.initials: M
authors.lastname: Pascual
authors.affiliation: Transplantation Center, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; Service of Infectious Diseases, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Meylan
authors.affiliation: Service of Infectious Diseases, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Bochud
mesh_terms: D015331:Cohort Studies; D037582:Complement Pathway, Mannose-Binding Lectin; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006084:Graft Rejection / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D015994:Incidence; D016030:Kidney Transplantation; D037102:Lectins / Q000235:genetics*; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood / Q000235:genetics*; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013557:Switzerland / Q000453:epidemiology; D000097604:Ficolins
chemical_list: D037102:Lectins; D037601:Mannose-Binding Lectin; D050606:Mannose-Binding Protein-Associated Serine Proteases; D000097604:Ficolins; C445619:MBL2 protein, human; C105296:MASP2 protein, human
keywords: acute rejection; cohort study; innate immunity; kidney transplantation; mannose-binding lectin