Polymorphisms in the lectin pathway of complement activation influence the incidence of acute rejection and graft outcome after kidney transplantation.

Golshayan, Déla; Wójtowicz, Agnieszka; Bibert, Stéphanie; Pyndiah, Nitisha; Manuel, Oriol; Binet, Isabelle; Buhler, Leo H; Huynh-Do, Uyen; Mueller, Thomas; Steiger, Jürg; Pascual, Manuel; Meylan, Pascal; Beldi, Guido; Semmo, Nasser; Mohacsi, Paul; Bochud, Pierre-Yves; Swiss Transplant Cohort Study, The (2016). Polymorphisms in the lectin pathway of complement activation influence the incidence of acute rejection and graft outcome after kidney transplantation. Kidney international, 89(4), pp. 927-938. Elsevier 10.1016/j.kint.2015.11.025

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Kardiologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Kardiologie 04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie 04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie 04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Nephrologie / Hypertonie 04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
UniBE Contributor:	Huynh-Do, Uyen, Beldi, Guido Jakob Friedrich, Semmo, Nasser, Mohacsi, Paul
Subjects:	600 Technology > 610 Medicine & health
ISSN:	1523-1755
Publisher:	Elsevier
Language:	English
Submitter:	Lilian Karin Smith-Wirth
Date Deposited:	10 Feb 2017 14:17
Last Modified:	05 Dec 2022 15:01
Publisher DOI:	10.1016/j.kint.2015.11.025
PubMed ID:	26924055
Uncontrolled Keywords:	acute rejection; cohort study; innate immunity; kidney transplantation; mannose-binding lectin
URI:	https://boris.unibe.ch/id/eprint/93404