We observed that near than 50% of PBMC were positive. NFRKB was highly expressed in a diffuse fashion in nuclear as well as in the cytoplasm compartments during the relapse phase, while in remission, its expression was lower and restricted to cytoplasm compartment. To determine whether NFRKB is expressed by a particular subpopulation of PBMC, we immunoblotted protein extracts from cell fractions isolated by immunoselection of PBMC from patients with relapse. The Fig. 4 shows that NFRKB was mostly upregulated in CD4+T cells and B cells from relapse, with a lesser amount produced in monocytes. The discrepancy between the apparent molecular weight detected in Jurkat cells and in MCNS patients led us to investigate whether NFRKB was differentially spliced in the disease. We performed Northern-blot analysis using total RNA from patients with relapse. We only visualized a 5.2 kb-transcript, which comigrates with the mature NFRKB mRNA detected in jurkat cells. These results suggest that patients with MCNS did not display abnormal spliced NFRKB forms, but that the posttranslational modifications likely account for the higher observed bands. Sumoylation of NFRKB is consistent with its function in transcriptional regulation. Sumoylation can either enhance or inhibit the transcription of target genes, although a majority of studies have identified a functional role of sumoylation in transcriptional repression. Because NFRKB was highly sumoylated in MCNS relapse, while the NFRKB protein detected by Western blotting in HEK cells after transfection was primarily non sumoylated, we cannot conclude whether NFRKB enhances or represses transcription in vivo, notably in relapse. Sumoylation may also regulate the nucleo-cytoplasmic traffic of proteins. AP-1 activation occurs in response to a wide range of stimuli involved in cellular processes, which promote proliferation, differentiation, survival and apoptosis. AP-1 protein function is regulated primarily by phosphorylation and by redox potential. In unstimulated T cells, AP-1 expression is low, but there is a rapid induction of AP-1 activity after T cell stimulation. The lack of AP-1 activation correlated with markedly decreased IL-2 synthesis and anergic T cells exhibit defective AP-1 activity. AP-1 regulates at least in part a number of cytokines directly or through a cooperation with other transcription factors. Although both Th1 and Th2 express AP-1 after activation, higher levels of c-Fos and c-Jun are found in Th2 cells. B cell activation, both T cell–dependent and T cell-independent can lead to AP-1 activation, through recruitment of PKC and/or CD40 pathways. The potential roles of epigenetic alterations in the pathogenesis of MCNS disease are suspected on the following arguments: 1) MCNS relapses are frequently triggered by an external or internal environmental factor including viral infection, toxin, nutriments, exposition to chemical products and stress. 2) A genetic defect cannot explain the relapsing-remitting profile of the disease but epigenetic alterations may occur without a direct change in the genetic sequence and are potentially reversible. 3) Epigenetic alterations have been reported in autoimmune disease with frequent/remission phases such as systemic lupus erythematosus and rheumatic SAR131675 diseases. 4) Steroid therapy may induce remission by reversing epigenetic changes.