Increased nitric oxide production by T- and B-cells in idiopathic nephrotic syndrome

Abstract

The pathogenesis of idiopathic nephrotic syndrome (INS) remains unclear. To study the role of nitric oxide (NO) in INS, we measured intracellular NO produced by T- and B-cells using a novel fluorescent indicator. Twelve children with INS (mean age 7.3 years; group A-1: in relapse, group A-2: in remission) were enrolled in the study together with 16 children with other renal diseases (9.5 years; group B) and 42 healthy control children (7.7 years; group C). The amount of NO produced by CD3+ cells (T-cells) and CD19+ cells (B-cells) and of plasma NO(x) was measured by flow cytometry and colorimetry, respectively. The average amount of NO produced by CD3+ and CD19+ cells in group A-1 subjects was significantly higher than that produced by these cells in group A-2 and B patients and the healthy controls (group C), respectively (P < 0.01), and it decreased after the patients achieved remission (P < 0.01). Plasma NO(x) levels in group A-1 patients was also highest among the different groups (P < 0.01). There were no significant differences in intracellular NO and plasma NO(x) among group A-2, B, and C subjects (P > 0.05). A significant correlation between plasma NO(x) and urinary protein excretion was found only in group A patients and not in group B patients. We conclude that an aberrant immune system may exist not only in T-cells but also in B-cells, and NO may play some role in INS.

The specific free radical scavenger edaravone suppresses fibrosis in the bleomycin-induced and tight skin mouse models of systemic sclerosis

“…In addition, bleomycin itself directly stimulates inflammatory cells (11, 37). Previous studies indicate that free radical production is increased in stimulated immune cells (38–40), and in the present study, bleomycin enhanced H 2 O 2 and NO production by B cells, macrophages, and neutrophils (Figure 4). Similar to findings in mice with bleomycin‐induced SSc, oxidative stress plays important roles in fibrosis in TSK/+ mice (16, 41).…”

Rituximab in post-transplant pediatric recurrent focal segmental glomerulosclerosis

“…There has been some suggestion in the literature that B cells may be involved in the pathogenesis of focal segmental glomerulosclerosis (FSGS) by releasing a permeability factor or by abnormal cross talk with T cells [4, 5]. The paucity of treatment options and the serendipitous finding of resolution of proteinuria while treating other conditions like idiopathic thrombocytopenic purpura (ITP) [6] and post-transplant lymphoproliferative disorder (PTLD) [7, 8] has led to the use of rituximab (RTX) for recFSGS and there arefew case reports suggesting its utility [9-14].…”

Novel Use of Rituximab for Steroid-Dependent Nephrotic Syndrome in Children

“…Based on this concept, it has been postulated that steroid and diverse immunosuppressants induce remission and prevent relapses via their suppressive effects on T cells [1]. However, a number of recent clinical observations provided evidence of an important role for B cells in the development of NS including our study [27,28,29]. In fact, RTX can be effective in treating patients with refractory NS [6,7,30] while it has been successfully used in patients with B-cell lymphoma and autoimmune disease such as systemic lupus erythematosus [31].…”