Anti-CD53 monoclonal antibody, clone OX-44

Acute rejection (AR) in kidney transplants remains a major cause of allograft failure. This study investigates the association between gene networks and AR in human kidney transplant biopsies with weighted gene co-expression network analysis (WGCNA). The gene expression profiles of 403 (training set) and 702 (validation set) kidney transplant patients' biopsies were analyzed. WGCNA was conducted, and 11 co-regulated gene modules were identified. Each module was investigated with a t-test for AR and survival analysis for graft loss. The association between modules and AR molecular subtypes was also evaluated. Three transcriptional gene modules were associated with AR and graft loss of kidney transplant. One module constitutes unregulated immune response genes in AR and is associated with shorter graft survival (HR = 4.22, p-value = 4.29 x 10(-6)). This module is more significantly up-regulated in T cell-mediated acute rejection (TCMR) than in non-TCMRs. Hub genes such as HLA-DMA, CORO1A, PYCARD, and CD53 were identified. The expression of the other two modules was down-regulated in AR patients and associated with a good graft prognosis (HR = 0.41 and 0.24, respectively). A systems biology network approach may help uncover gene networks in kidney transplant biopsies associated with AR and contribute to identifying new biomarkers.

Cell surface proteins of the transmembrane 4 superfamily (TM4SF) are a newly characterized family of proteins which are presumed to span the plasma membrane four times. The function of this family of molecules is poorly understood, but based on monoclonal antibody studies there is some evidence that they may be involved in transmembrane signal transduction and regulation of cell proliferation, differentiation, or both, in a number of different cell types. CD53 is a member of this family that is expressed on leukocytes, and transduces activation signals through unknown mechanisms that may involve phosphorylation events. However, CD53 has never been shown to associate directly with kinases. Here, we show by immunoprecipitation from cell lysates of lymph nodes and a thymoma cell line, that immune complexes of rat CD53 contain tyrosine phosphatase activity. The CD53-associated phosphatase was able to dephosphorylate in vitro the phosphorylated tyrosine kinase Lck, as well as a synthetic substrate, and its activity was abrogated by a tyrosine phosphatase inhibitor. Although its identity has not been established, it is clear from depletion experiments that it is not CD45. CD63, a second member of the TM4SF, also co-precipitates a phosphatase activity from rat basophilic leukemia cells. These results demonstrate that the TM4SF members associate with tyrosine phosphatases. It seems possible that such associated phosphatases may contribute to the signal transduction capacity of TM4SF molecules.