Search

The alternative pathway of complement originated from the Properdin pathway originally described by the Pillemer laboratory in the 1950s. This work generated great controversy and it took several decades for a consensus on its components, its reaction sequence and its functions to emerge. This paper reviews this history and attempts to clarify some of the ambiguities that remain. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In this issue of the Journal of Heart and Lung Transplantation , Marrón-Liñares et al report the results of an interesting study in which they evaluated 51 genes associated with the complement pathway in a small number of heart recipients to explore their relationship with antibody-mediated rejection (AMR). Next-generation sequencing was used in 46 heart transplant recipients (23 with AMR and 23 without AMR). The authors identified a significant association of 2 single-nucleotide polymorphisms with the absence or presence of AMR, respectively, p.Gly54Asp-MBL2 in the mannose-binding lectin (MBL) 2 gene and p.Asn428(p=)-CFP in the alternative complement factor properdin (CFP) gene. This article is a new contribution to the heart transplant literature. It suggests that complement single-nucleotide polymorphisms may influence circulating levels of selected proteins of both the lectin pathway and alternative complement pathways, thus potentially determining which patients will develop AMR. [ABSTRACT FROM AUTHOR]