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Donor‐specific antibody (DSA) is an independent risk factor for antibody‐mediated rejection (ABMR) and graft loss. The C1q assay differentiates complement from non‐complement‐binding DSA and C1q‐binding DSA may lead to poor allograft survival. Our aim was to characterize the type of DSA seen in pediatric kidney transplant recipients and to determine whether complement binding DSA was associated with inferior graft survival.This was a single‐center retrospective study of 48 children who were transplanted between 2009 and 2016. DSA were monitored using Luminex single antigen beads. A negative crossmatch was required to proceed with transplantation. The median follow‐up time was 4.9 (3.4, 7.9) years. The median age was 12 (5.7, 15.4) years. DSA developed in 27/48 (56.3%), while C1q‐binding DSA developed in 17/27 (63%). There were no significant differences between DSA negative, C1q‐binding DSA, and C1q negative DSA, with regard to the number of HLA‐ABDR (P =.09) or HLA‐DQ mismatches alone (P =.16). For both C1q negative and C1q‐binding DSA, DQ was the most common target of the DSA (19/27; 70.4%). C1q‐binding DSA was associated with a significantly higher frequency of biopsy proven rejection (76.5%) when compared to C1q negative (10%) and DSA negative (14.3%); P =.001. Graft loss was seen in 6 (12.5%), all of whom had C1q‐binding DSA (P =.004). C1q‐binding DSA was most commonly directed to DQ antigens. C1q‐binding DSA was associated with increased rejection and graft loss. Monitoring for C1q‐binding DSA may risk stratify recipients and guide physician management. [ABSTRACT FROM AUTHOR]

Nucleolin (NCL) is an abundant stress-responsive, RNA-binding phosphoprotein that controls gene expression by regulating either mRNA stability and/or translation. NCL binds to the AU-rich element (ARE) in the 3′UTR of target mRNAs, mediates miRNA functions in the nearby target sequences, and regulates mRNA deadenylation. However, the mechanism by which NCL phosphorylation affects these functions and the identity of the deadenylase involved, remain largely unexplored. Earlier we demonstrated that NCL phosphorylation is vital for cell cycle progression and proliferation, whereas phosphorylation-deficient NCL at six consensus CK2 sites confers dominant-negative effect on proliferation by increasing p53 expression, possibly mimicking cellular DNA damage conditions. In this study, we show that NCL phosphorylation at those CK2 consensus sites in the N-terminus is necessary to induce deadenylation upon oncogenic stimuli and UV stress. NCL-WT, but not hypophosphorylated NCL-6/S*A, activates poly (A)-specific ribonuclease (PARN) deadenylase activity. We further demonstrate that NCL interacts directly with PARN, and under non-stress conditions also forms (a) complex (es) with factors that regulate deadenylation, such as p53 and the ARE-binding protein HuR. Upon UV stress, the interaction of hypophosphorylated NCL-6/S*A with these proteins is favored. As an RNA-binding protein, NCL interacts with PARN deadenylase substrates such as TP53 and BCL2 mRNAs, playing a role in their downregulation under non-stress conditions. For the first time, we show that NCL phosphorylation offers specificity to its protein-protein, protein-RNA interactions, resulting in the PARN deadenylase regulation, and hence gene expression, during cellular stress responses. [ABSTRACT FROM AUTHOR]