Increased apoptosis of peripheral blood lymphocytes in children with nephrotic syndrome

Zachwieja, Jacek; Dworacki, Grzegorz; Bobkowski, Waldemar; Dobrowolska, Agnieszka; Zaniew, Marcin; Maciejewski, J

doi:10.1007/s00467-001-0782-1

Cited by 31 publications

(28 citation statements)

References 19 publications

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“…One recent study suggested a role of apoptosis as explanation of abnormal function and number of lymphocytes; however, this cannot explain the divergent findings of specific subpopulations [28]. Furthermore the increased apoptotic rate was only present in relapse and not in remission and is therefore not able to explain all results.…”

Section: Discussionmentioning

confidence: 48%

“…The positive correlation of CD8+ and IgM for the first time links studies of the cellular and humoral immune system in SSNS and indicates a potential role in the suggested defective switch from IgM to IgG synthesis in SSNS, but this has not been proven yet and warrants further study. In general, further study especially of CD8 lymphocyte function is clearly needed, especially since recent data demonstrate that this subset is involved in cytokine production in SSNS [22]. By this alone [23], this subset may be a key player in the pathogenesis of this disorder.…”

Section: Discussionmentioning

confidence: 99%

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Changes of Lymphocyte Populations in Pediatric Steroid-Sensitive Nephrotic Syndrome Are More Pronounced in Remission than in Relapse

et al. 2005

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Background/Aim: Although clinical and immunological findings in steroid-sensitive nephrotic syndrome (SSNS) favor an immunopathogenesis, many issues remain unsolved. Comprehensive studies analyzing cellular and humoral immunity in SSNS are scarce, and few studies addressed the effect of steroids on immunological factors. Methods: We therefore performed a cross-sectional study of T and B lymphocyte populations in 89 children during the different stages of the disease and related the findings to parameters of humoral immunity and treatment with steroids. Results: In untreated relapse, an increase in the proportion of activated CD3+ lymphocytes with a concomitant reduction of CD19+ B cells was noted compared to healthy controls. Conversely, patients with steroid dependency, relapsing on alternate-day steroids, showed a decline of the absolute numbers as well as proportion of CD4+ lymphocytes but a relative increase in CD19+ B cells, compared to healthy controls. Also untreated remission was characterized by an absolute and relative decrease in CD4+ lymphocytes compared to healthy controls which was accompanied by a significant increase in the proportion of CD8+ and also activated CD3+ lymphocytes. Steroid-induced remission resulted in suppression of absolute and relative CD4+, while absolute and relative B cells were upregulated in this group compared to untreated remission. Summary and Conclusion: Alterations of lymphocyte populations in SSNS are not limited to relapse but seem to be more pronounced in remission and show a different profile with steroid treatment. Changes of lymphocyte populations do not only affect T but also B lymphocytes, which may be of relevance in the pathogenesis of this disorder.

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Section: Discussionmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Changes of Lymphocyte Populations in Pediatric Steroid-Sensitive Nephrotic Syndrome Are More Pronounced in Remission than in Relapse

et al. 2005

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“…This was in contrast to the published study by Gulati et al (4), in which patients with late steroid + expression in FSGS rituximab responders compared with those in both nonresponders and controls, and it was associated with significantly reduced mitogen-stimulated CD3 production of IFN-g and IL-2. The baseline immunologic signature in our FSGS rituximab responders was also significantly different from that in patients with MCNS in relapse as shown in Table 3, indicating that the immunologic basis underlying the nephrotic syndrome is likely to be distinct in this group of FSGS rituximab responders compared with those in patients with MCNS, in whom increased mitogen-stimulated lymphocyte production of IL-2 and IFN-g has been shown (27)(28)(29)(30)(31).…”

Section: Discussionmentioning

confidence: 79%

T Lymphocyte Activation Markers as Predictors of Responsiveness to Rituximab among Patients with FSGS

Chan

Liu

Resontoc

et al. 2016

CJASN

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Background and objectives Rituximab is used with variable success in difficult FSGS. Because B cell depletion significantly affects T cell function, we characterized T cell subsets in patients with FSGS to determine if an immunologic signature predictive of favorable response to rituximab could be identified.Design, setting, participants, & measurements Twenty-two consecutive patients with FSGS (median age =14.4 years old; range =6.2-25.0 years old) and age of onset of nephrotic syndrome 1-18 years old receiving rituximab for clinical indications between October of 2009 and February of 2014 were studied. Indications for rituximab were lack of sustained remission despite calcineurin inhibitors (CNIs) and mycophenolate in steroid-resistant patients and lack of steroid-sparing effect with cyclophosphamide and CNI or CNI toxicity in steroid-dependent patients. Exclusion criteria were infantile onset, known genetic mutations, and secondary causes. Rituximab (375 mg/m 2 ) was given fortnightly up to a maximum of four doses. Immunologic subset monitoring was performed at baseline and regular intervals until relapse. Median follow-up duration postrituximab was 26.7 months (range =6.5-66.5 months). Baseline immunologic subsets were examined for association with rituximab response defined as resolution of proteinuria with discontinuation of prednisolone and CNI 3 months postrituximab.Results Twelve patients (54.5%) responded to rituximab. Mitogen-stimulated CD154 + CD4 + CD3 + subset before rituximab was significantly lower in FSGS responders compared with nonresponders (54.9%628.1% versus 78.9%616.4%; P=0.03). IFN-g + CD3 + and IL-2 + CD3 + were similarly decreased in responders compared with nonresponders (0.6%60.8% versus 7.5%66.1%; P=0.003 and 0.2%60.5% versus 4.0%64.7%; P,0.01, respectively). Recovery of all three activation subsets occurred 6 months postrituximab treatment (CD154 + CD4 + CD3 + , 74.8%617.2%; IFN-g + CD3 + , 7.1%67.7%; and IL-2 + CD3 + , 7.9%610.9%; P,0.01). Receiver-operating characteristic analysis using optimal cutoff values showed that activated CD154 + CD4 + CD3 + ,83.3% (area under the curve [AUC], 0.81; 95% confidence interval [95% CI], 0.61 to 1.00), IFN-g + CD3 + ,2.5% (AUC, 0.90; 95% CI, 0.75 to 1.00), and IL-2 + CD3 + ,0.3% (AUC, 0.78; 95% CI, 0.57 to 0.98) were good predictors of rituximab response.Conclusions We have identified prognostic markers that define a subset of patients with FSGS bearing an immunologic signature representing hyporesponsiveness to T cell stimulation and therefore, who respond better to rituximab.

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“…In contrast, few studies supported a Th1-dominant response in MCD. For example, Zachwieja et al [26] described an increased expression of IL-2, another Th1 cytokine, in their flow cytometry experiments. Although our study also showed a moderate expression of Th1 cytokine IFN-γ in MCD, its expression level was significantly lower than that of IL-4.…”

Section: Discussionmentioning

confidence: 99%

Coincident Activation of Th2 T Cells with Onset of the Disease and Differential Expression of GRO-Gamma in Peripheral Blood Leukocytes in Minimal Change Disease

et al. 2007

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Background: Involvement of Th2 T cells/NFĸB in minimal change disease (MCD) has been postulated. A promising but unconfirmed glomerular permeability factor (GPF) from MCD T cells has been described. We explored whether GPF was the consequence of Th2 cell activation. Methods: Peripheral blood leukocytes (PBL) from 16 MCD patients and 7 normal controls were analyzed and the results were statistically compared. Results: Flow cytometry demonstrated a significant expansion of CD4+ T cell population and dramatically increased CD69+ cells among CD4+ T cells in MCD, suggesting coincident activation of T cells with onset of the disease. RT-PCR on RNA from either freshly isolated PBL or post in vitroactivation showed high-level expression of the Th2 cytokine interleukin-4 in all MCD patients. Importantly, both antibody microarray assay on sera and RT-PCR on mRNA of PBL revealed expression of a CXC chemokine GRO-γ (growth-related oncogene) in all MCD patients as compared with one of 7 controls. Conclusions: Our results reveal an association between onset of MCD and activation of Th2 cells. The GRO family has been implicated in the function of endothelial cells, and its expression is under NFĸB regulation. Thus, GRO-γ is a promising candidate for Th2-associated GPF in MCD.

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Increased apoptosis of peripheral blood lymphocytes in children with nephrotic syndrome

Cited by 31 publications

References 19 publications

Changes of Lymphocyte Populations in Pediatric Steroid-Sensitive Nephrotic Syndrome Are More Pronounced in Remission than in Relapse

Changes of Lymphocyte Populations in Pediatric Steroid-Sensitive Nephrotic Syndrome Are More Pronounced in Remission than in Relapse

T Lymphocyte Activation Markers as Predictors of Responsiveness to Rituximab among Patients with FSGS

Coincident Activation of Th2 T Cells with Onset of the Disease and Differential Expression of GRO-Gamma in Peripheral Blood Leukocytes in Minimal Change Disease

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