title: Low level of MAp44, an inhibitor of the lectin complement pathway, and long-term graft and patient survival; a cohort study of 382 kidney recipients.
abstract: Higher incidence of malignancy and infectious diseases in kidney transplant recipients is related to immunosuppressive treatment after transplantation and the recipient's native immune system. The complement system is an essential component of the innate immunity. The aim of the present study was to investigate the association of effector molecules of the lectin complement pathway with graft and patient survival after kidney transplantation.
  
  
  
  Two mannan-binding lectin (MBL) associated proteases, MASP-2 and MASP-3 (activators of the lectin pathway) and two MBL-associated proteins, MAp44 and MAp19 (inhibitors of the lectin pathway) were measured at the time of transplantation in 382 patients (≥17 years old) transplanted in 2000-2001. The cohort was followed until December 31, 2014. Data on patient and graft survival were obtained from the Norwegian Renal Registry. Cox proportional hazard regression models were performed for survival analyses.
  
  
  
  Low MAp44 level (1st versus 2-4 quartile) was significantly associated with overall mortality; HR 1.52, 95 % CI 1.08-2.14, p = 0.017. In the sub analyses in groups below and above median age (51.7 years), low MAp44 as a predictor of overall mortality was statistically significant only in recipients of ≤51.7 years; HR 2.57, 95 % CI 1.42-4.66, p = 0.002. Furthermore, low MAp44 was associated with mortality due to infectious diseases; HR 2.22, 95 % CI 1.11-4.41, p = 0.023. There was no association between MASP-2, MASP-3 or MAp19 levels and patient mortality. No association between any measured biomarkers and death censored graft loss was found.
  
  
  
  Low MAp44 level at the time of transplantation was associated with increased overall mortality in kidney recipients of median age of 51.7 years or below and with mortality due to infectious diseases in the whole patient cohort after nearly 14-years of follow up after transplantation. No associations between other effector molecules; MASP-2, MASP-3 or MAp19 and recipient mortality were found, as well as no association of any biomarker with death censored graft loss.
authors.affiliation: Department of Nephrology, Ullevål Oslo University Hospital, Postbox 4950, Nydalen, 0424, Oslo, Norway. yulsme@uus.no.|Faculty of Medicine, University of Oslo, Oslo, Norway. yulsme@uus.no.
authors.forename: Julia
authors.identifier: 0000-0003-2189-9767
authors.initials: J
authors.lastname: Smedbråten
authors.affiliation: Department of Transplant Medicine, Rikshospitalet Oslo University Hospital, Oslo, Norway.
authors.forename: Geir
authors.initials: G
authors.lastname: Mjøen
authors.affiliation: Faculty of Medicine, University of Oslo, Oslo, Norway.|Department of Transplant Medicine, Rikshospitalet Oslo University Hospital, Oslo, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Hartmann
authors.affiliation: Department of Transplant Medicine, Rikshospitalet Oslo University Hospital, Oslo, Norway.|Norwegian Renal Registry, Oslo University Hospital, Oslo, Norway.|School of Pharmacy, University of Oslo, Oslo, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Åsberg
authors.affiliation: Faculty of Medicine, University of Oslo, Oslo, Norway.|Department of Microbiology, Rikshospitalet Oslo University Hospital, Oslo, Norway.
authors.forename: Halvor
authors.initials: H
authors.lastname: Rollag
authors.affiliation: Faculty of Medicine, University of Oslo, Oslo, Norway.|Department of Immunology, Rikshospitalet Oslo University Hospital and K.G Jebsen IRC, University of Oslo, Oslo, Norway.|Research Laboratory, Nordland Hospital, Bodø, and Faculty of Health Sciences, K.G.Jebsen TREC, University of Tromsø, Tromsø, Norway.|Center of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Tom Eirik
authors.initials: TE
authors.lastname: Mollnes
authors.affiliation: Oslo Centre for Biostatistics and Epidemiology, Research Support Services, Oslo University Hospital, Oslo, Norway.
authors.forename: Leiv
authors.initials: L
authors.lastname: Sandvik
authors.affiliation: Oslo Centre for Biostatistics and Epidemiology, Research Support Services, Oslo University Hospital, Oslo, Norway.
authors.forename: Morten W
authors.initials: MW
authors.lastname: Fagerland
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Steffen
authors.initials: S
authors.lastname: Thiel
authors.affiliation: Department of Nephrology, Ullevål Oslo University Hospital, Postbox 4950, Nydalen, 0424, Oslo, Norway.
authors.forename: Solbjørg
authors.initials: S
authors.lastname: Sagedal
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D037582:Complement Pathway, Mannose-Binding Lectin / Q000276:immunology*; D005260:Female; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007239:Infections / Q000401:mortality*; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000401:mortality*; D037102:Lectins / Q000378:metabolism; D008297:Male; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000378:metabolism*; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012042:Registries; D015996:Survival Rate; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D037102:Lectins; C084067:MASP1 protein, human; C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases
keywords: Complement; Kidney transplantation; Recipient survival