C4d

C4d is an inactive substance produced by C4 cleavage in the classical complement pathway. It can covalently bind to tissues with long half-life and high stability. So the positive expression of C4d is considered as a hallmark of complement system activation. Some research found that C4d can deposit in peritubular capillary endothelium of renal tubules, indicating that the body has activated humoral immune rejection. Therefore, the C4d staining results have important guiding significance for the treatment and prognosis of organ transplant patients. Later, C4d was found to be expressed in glomerular mesangium of IgA nephropathy (IgAN), which is an independent risk factor for the progression of IgAN to end-stage renal disease. Meanwhile, C4d assist in distinguishing between membranous nephropathy (+) and minimal change nephropathy (-). In addition, some scholars pointed out that the deposition of C4d in follicular dendritic cells (FDCs) of follicular lymphoma (FL) can serve as a specific indicator for FL diagnosis. This is because FDCs contain Fc receptors that can aggregate immune complexes and trigger complement reaction.