Low mannose-binding lectin serum levels are associated with reduced kidney graft survival

Bay, Jakob Thaning; Sørensen, Søren Schwartz; Hansen, Jesper Melchior; Madsen, Hans O.; Garred, Peter

doi:10.1038/ki.2012.373

Cited by 30 publications

(26 citation statements)

References 41 publications

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“…Previous reports either did not find a significant association between MBL status and acute rejection 36 or concentrated on long-term graft and patient outcomes. 16,17,26 The finding of robust and clear-cut association between low MBL status and increased incidence of ACR seen in our study is likely due to size and homogeneity of the prospectively followed cohort being treated with recent-era immunosuppressive protocols. Moreover, the relatively homogeneous drug prescription, in ), B (G54D, rs1800450), and C (G57E, rs1800451), respectively, and the wild-type allele of each is referred to as genotype A. MBL genotype Y refers to presence of rare variant C of promoter SNP G221C (rs7096206) and genotype X as wild-type allele G of that polymorphism.…”

Section: Golshayan Et Al: Lectin Pathway and Rejection After Transmentioning

confidence: 69%

“…Recently, Bay et al have used a lower median cutoff value (#454 ng/ml) and have shown that low serum MBL levels were associated with decreased 5-year death-censored graft survival. 26 Interestingly, the strongest association was seen in non-immunized patients receiving a kidney from a deceased donor. 26 When stratifying our data, we also observed a strongest association between low MBL status and ACR in recipients of deceased as compared to living donors (Supplementary Figures S4 and S5).…”

Section: L I N I C a L I N V E S T I G A T I O Nmentioning

confidence: 99%

“…[20][21][22][23][24] Conflicting data exist on the deleterious versus protective role of the lectin pathway of complement activation in graft rejection, as well as in patient and graft outcomes after SOT. [25][26][27][28] Many of the available studies in kidney transplantation are either retrospective, involve small numbers of patients, or have analyzed outcomes under previous eras of immunosuppression and anti-infectious therapies. Therefore, the aim of the present study was to investigate the role of the lectin pathway of complement activation and the possible association between recipient genotype and graft outcomes after kidney transplantation in a large, well-characterized, ongoing prospective cohort.…”

mentioning

confidence: 99%

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

Golshayan¹,

Wójtowicz²,

Bibert³

et al. 2016

Kidney International

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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 antibodymediated 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.

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Section: Golshayan Et Al: Lectin Pathway and Rejection After Transmentioning

confidence: 69%

Section: L I N I C a L I N V E S T I G A T I O Nmentioning

confidence: 99%

mentioning

confidence: 99%

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

Golshayan¹,

Wójtowicz²,

Bibert³

et al. 2016

Kidney International

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“…A different study associated low MBL levels with poor renal allograft function and survival in non-HLA sensitised patients [56]. These differences may arise from the detection assay used with different antibodies binding high or low-order oligomers of MBL.…”

Section: Complement Activation Pathways In Ir Injurymentioning

confidence: 99%

Complement—here, there and everywhere, but what about the transplanted organ?

Montero

Sacks

Smith

2016

Seminars in Immunology

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The part of the innate immune system that communicates and effectively primes the adaptive immune system was termed "complement" by Ehrlich to reflect its complementarity to antibodies having previously been described as "alexine" (i.e protective component of serum) by Buchner and Bordet. It has been established that complement is not solely produced systemically but may have origin in different tissues where it can influence organ specific functions that may affect the outcome of transplanted organs. This review looks at the role of complement in particular to kidney transplantation. We look at current literature to determine whether blockade of the peripheral or central compartments of complement production may prevent ischaemic reperfusion injury or rejection in the transplanted organ.We also review new therapeutics that have been developed to inhibit components of the complement cascade with varying degrees of success leading to an increase in our understanding of the multiple triggers of this complex system. In addition, we consider whether biomarkers in this field are effective markers of disease or treatment. Word count 169

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“…Its carbohydrate recognition domains bind in a calciumdependent manner to patterns of carbohydrate residues found on microorganisms. MBL exerts an important role in the innate immune system, and several studies have indicated that low levels of MBL affect the outcome of infectious diseases, critical illness, and kidney graft survival (8)(9)(10). Interestingly, high levels of MBL offer protection against invading microorganisms but may confer biological disadvantages in other situations (11).…”

mentioning

confidence: 99%

Serum Mannose-Binding Lectin Is a Strong Biomarker of Diabetic Retinopathy in Chinese Patients With Diabetes

et al. 2015

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OBJECTIVEInflammation and complement activation initiated by mannose-binding lectin (MBL) may be implicated in the pathogenesis of diabetic vascular complications. We investigated serum MBL levels in patients with diabetes with and without diabetic retinopathy (DR). RESEARCH DESIGN AND METHODSSerum MBL levels were determined in 348 patients with diabetes and in 100 healthy control subjects. The prediction value of MBL was compared with diabetes duration, hs-CRP, and other known predictors. Multivariate analyses were performed using logistic regression models. RESULTSMBL levels on admission were significantly increased in patients with diabetes with DR (P < 0.0001) and vision-threatening DR (VTDR; P < 0.0001). Multivariate logistic regression analysis adjusted for common indictors showed that serum MBL levels ‡3,385 mg/L were an independent predictor of DR (odds ratio [OR] 3.14, 95% CI 1.77-5.57) and VTDR (OR 7.83,). The area under the receiver operating characteristic curve of MBL was 0.81 (95% CI 0.76-0.86) for DR and 0.84 (95% CI 0.74-0.93) for VTDR. CONCLUSIONSThe current study demonstrated that MBL appears to be an independent biomarker for DR in the Chinese population, suggesting a possible role of MBL in the pathogenesis of DR complications in diabetes.Diabetes has become a major public health problem in China. In 2009, the agestandardized prevalence of diabetes was 9.7%, accounting for 92.4 million adults with diabetes (1). Diabetic retinopathy (DR) is the leading cause of blindness among working-aged adults around the world (2). Approximately 29% of U.S. adults with type 2 diabetes have DR (3), whereas DR will develop in 95% of individuals with type 1 diabetes during their lifetime (4).The presence of DR was associated with an increased risk of all-cause mortality and cardiovascular events in patients with diabetes (5). However, risk of vision loss due to DR retinopathy can be reduced by effective control of serum glucose and blood pressure (BP). The efficacy and cost-effectiveness of early detection and treatment of DR is well established (6). Although the major risk factors for

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Low mannose-binding lectin serum levels are associated with reduced kidney graft survival

Cited by 30 publications

References 41 publications

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

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

Complement—here, there and everywhere, but what about the transplanted organ?

Serum Mannose-Binding Lectin Is a Strong Biomarker of Diabetic Retinopathy in Chinese Patients With Diabetes

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