Assessment of the complement-binding capacity of donor-specific anti-HLA antibodies appears to be useful in identifying patients at high risk for kidney-allograft loss.

Immune rejection of organ transplants is a life-threatening complication and is exemplified by alterations in the expression of proteinencoding genes. Because microRNAs (miRNAs) regulate the expression of genes implicated in adaptive immunity, we investigated whether acute rejection (AR) is associated with alterations in miRNA expression within allografts and whether expression profiles are diagnostic of AR and predict allograft function. Seven of 33 renal allograft biopsies (12 AR and 21 normal) were profiled using microfluidic cards containing 365 mature human miRNAs (training set), and a subset of differentially expressed miRNAs were quantified in the remaining 26 allograft biopsies (validation set). We found a strong association between intragraft expression of miRNAs and messenger RNAs (mRNAs), and that AR, and renal allograft function, could be predicted with a high level of precision using intragraft levels of miRNAs. Our investigation of miRNA expression in normal human peripheral blood mononuclear cells (PBMCs) showed that miRNAs (miR-142-5p, -155, and -223) overexpressed in AR biopsies are highly expressed in PBMCs, and that stimulation with the mitogen phytohaemagglutinin results in an increase in the abundance of miR-155 and a decrease in miR-223 and let-7c. Quantification of miRNAs in primary cultures of human renal epithelial cells (HRECs) showed that miR-30a-3p, -10b, and let-7c are highly expressed in HRECs, and that stimulation results in a decreased expression of miR-30a-3p. Our studies, in addition to suggesting a cellular basis for the altered intragraft expression of miRNAs, propose that miRNA expression patterns may serve as biomarkers of human renal allograft status.acute rejection ͉ biomarkers ͉ miRNA ͉ renal transplantation ͉ mRNA A n important breakthrough in biology in recent years is the discovery of microRNAs (miRNAs) (1). miRNAs are small (Ϸ19-25 nucleotides), naturally occurring, evolutionarily conserved, abundant, and noncoding RNAs that regulate gene expression, primarily by translational repression or by messenger RNA (mRNA) degradation (2). The first miRNA was described in 1993 (3, 4) and hundreds of miRNAs have now been cloned and thousands predicted bioinformatically (5). It has been shown that a single miRNA is directly responsible for the repression of hundreds of proteins and regulating the levels of thousands of others (6). Many diverse biological processes such as development (7), cell proliferation, differentiation, apoptosis, fat metabolism, and oncogenesis (8) are reported to be regulated by miRNAs. Emerging data suggest a critical role for miRNAs in the regulation of immune cell development and in the modulation of innate and adaptive immune responses (9-12).Transplantation of organs has progressed from a risky experimental therapy to a safe and life-saving treatment modality in a relatively short span of 5 decades (13-15). However, transplant recipients require life-long treatment with nonspecific, toxic, and multiple immunosuppressive drugs and are ever under the t...