Th17/Treg imbalance in adult patients with minimal change nephrotic syndrome

Li, Lili; Qin, Yan; Cai, Jun; Wang, Haiyun; Jiang, Tao; Li, Hang; Chen, Limeng; Li, Mingxi; Li, Xuemei; Li, Xuewang

doi:10.1016/j.clim.2011.02.018

Cited by 115 publications

(88 citation statements)

References 26 publications

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“…Certainly, no single cytokine can be considered pathogenic per se in MCD, but rather may play a role in the context of a complex network with multiple cellular and circulating players (28). Moreover, different lines of evidence suggest a reduced function of regulatory T cells in MCD in adult patients (29). Confirming this, MCD has been observed in immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome, a congenital immunodeficiency with severe T regulatory cell hypofunction (30).…”

Section: Pathogenesismentioning

confidence: 77%

Minimal Change Disease

Vivarelli

Massella

Ruggiero

et al. 2016

CJASN

419

383

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Minimal change disease (MCD) is a major cause of idiopathic nephrotic syndrome (NS), characterized by intense proteinuria leading to edema and intravascular volume depletion. In adults, it accounts for approximately 15% of patients with idiopathic NS, reaching a much higher percentage at younger ages, up to 70%-90% in children >1 year of age. In the pediatric setting, a renal biopsy is usually not performed if presentation is typical and the patient responds to therapy with oral prednisone at conventional doses. Therefore, in this setting steroid-sensitive NS can be considered synonymous with MCD. The pathologic hallmark of disease is absence of visible alterations by light microscopy and effacement of foot processes by electron microscopy. Although the cause is unknown and it is likely that different subgroups of disease recognize a different pathogenesis, immunologic dysregulation and modifications of the podocyte are thought to synergize in altering the integrity of the glomerular basement membrane and therefore determining proteinuria. The mainstay of therapy is prednisone, but steroid-sensitive forms frequently relapse and this leads to a percentage of patients requiring second-line steroid-sparing immunosuppression. The outcome is variable, but forms of MCD that respond to steroids usually do not lead to chronic renal damage, whereas forms that are unresponsive to steroids may subsequently reveal themselves as FSGS. However, in a substantial number of patients the disease is recurrent and requires long-term immunosuppression, with significant morbidity because of side effects. Recent therapeutic advances, such as the use of anti-CD20 antibodies, have provided long-term remission off-therapy and suggest new hypotheses for disease pathogenesis.

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Section: Pathogenesismentioning

confidence: 77%

Minimal Change Disease

Vivarelli

Massella

Ruggiero

et al. 2016

CJASN

419

383

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“…19,31 Rituximab may also deplete the IL-17-producing CD4 + T cells (Th17), which express CD20 on their surface and have been implicated in the pathogenesis of the disease. 32,33 The anti-Th17 effect of rituximab formed the theoretical basis for its use in rheumatoid arthritis [34][35][36][37] and in small vessel vasculitis. 38 Finally, rituximab exerts direct and nonimmunologic effects on the podocyte.…”

Section: Discussionmentioning

confidence: 99%

Rituximab in Children with Steroid-Dependent Nephrotic Syndrome

Ravani

Rossi

Bonanni

et al. 2015

Journal of the American Society of Nephrology

164

142

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Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity from steroids or steroid-sparing agents. This open-label, noninferiority, randomized controlled trial at four sites in Italy tested whether rituximab is noninferior to steroids in maintaining remission in juvenile SDNS. We enrolled children age 1-16 years who had developed SDNS in the previous 6-12 months and were maintained in remission with high prednisone doses ($0.7 mg/kg per day). We randomly assigned participants to continue prednisone alone for 1 month (control) or to add a single intravenous infusion of rituximab (375 mg/m 2 ; intervention). Prednisone was tapered in both groups after 1 month. For noninferiority, rituximab had to permit steroid withdrawal and maintain 3-month proteinuria (mg/m 2 per day) within a prespecified noninferiority margin of three times the levels among controls (primary outcome). We followed participants for $1 year to compare risk of relapse (secondary outcome). Fifteen children per group (21 boys; mean age, 7 years [range, 2.6-13.5 years]) were enrolled and followed for #60 months (median, 22 months). Three-month proteinuria was 42% lower in the rituximab group (geometric mean ratio, 0.58; 95% confidence interval, 0.18 to 1.95 [i.e., within the noninferiority margin of three times the levels in controls]). All but one child in the control group relapsed within 6 months; median time to relapse in the rituximab group was 18 months (95% confidence interval, 9 to 32 months). In the rituximab group, nausea and skin rash during infusion were common; transient acute arthritis occurred in one child. In conclusion, rituximab was noninferior to steroids for the treatment of juvenile SDNS.

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“…An improvement in proteinuria coincided with a reduction in the Th17/Treg ratio and an increase in the Th1/Th2 ratio. A high Th17/Treg ratio has been previously observed in association with increased proteinuria and decreased serum albumin levels in primary MCD (8). Corticosteroid therapy has been demonstrated to result in a reduction in proteinuria and normalization of the Th17/Treg ratio due to a decrease in the Th17 cell population and an increase in the Treg cell population (8).…”

Section: Discussionmentioning

confidence: 98%

Alterations of immune cell subsets in relapsed, thymoma-associated minimal change disease: A case report

et al. 2015

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Abstract. The most frequently described glomerulopathy in patients with thymoma is minimal change disease (MCD). The present study reports the case of a 63-year-old female with recurrent thymoma and poorly-controlled paraneoplastic MCD, who was enrolled on a phase I/II clinical trial (no. NCT01100944) and treated with the histone deacetylase inhibitor, belinostat, in combination with cisplatin, doxorubicin and cyclophosphamide. Treatment resulted in a complete radiological response, a dramatic reduction in proteinuria and changes in immune cell subset composition, consisting of a reduction in the number of T helper (Th)1, Th2, Th17 and regulatory T cells. Changes in T-cell polarization were also observed with an increase in the Th1/Th2 ratio. To the best of our knowledge, the current study is the first to provide a detailed description of changes in immune cell subset composition in thymoma-associated MCD. Early administration of effective antitumor therapy should be considered in these cases, particularly when proteinuria is poorly controlled despite the use of steroids and other immunosuppressive therapies. IntroductionMinimal change disease (MCD) is a well-described glomerulopathy that accounts for 10-15% of primary nephrotic syndrome cases in adults (1). It is characterized by nephrotic-range proteinuria, edema, hypoalbuminemia, and hyperlipidemia. Biopsy findings include an absence of glomerular lesions on light microscopy and effacement of foot processes on electron microscopy. Steroids are used for first-line therapy of MCD. Immunomodulatory drugs such as cyclosporine, tacrolimus and mycophenolate mofetil are used for treatment of relapsed disease or in cases of steroid-resistance or steroiddependence (2,3). MCD is also the most common cause of paraneoplastic glomerulonephritis in patients with thymoma, and T-cell dysfunction is considered to play an important role in its pathogenesis (4). However, the impact of antitumor or immunosuppressive therapy on the immune system in patients with thymoma-associated MCD is poorly understood. The present study describes changes in immune cell subset composition in response to tumor-directed therapy in a patient with relapsed, thymoma-associated MCD, who achieved a complete radiological tumor response and durable reduction in proteinuria. Case reportA 63-year-old female with Masaoka stage IVA, World Health Organization type B2 thymoma (5,6) was referred for treatment of recurrent thymoma 3 years after the initial diagnosis. Initial treatment consisted of surgical resection. The patient had developed anasarca and acute kidney injury 7 months before presentation with recurrent thymoma. A renal biopsy showed no global sclerosis on light microscopy and diffuse foot process effacement on electron microscopy. These changes were consistent with MCD. Oral prednisone was administered at a dose of 80 mg/day, which was decreased to 20 mg/day after 1 month due to steroid-induced myopathy. Despite an initial reduction in proteinuria, MCD relapse was observed within 4 months (Fig....

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Th17/Treg imbalance in adult patients with minimal change nephrotic syndrome

Cited by 115 publications

References 26 publications

Minimal Change Disease

Minimal Change Disease

Rituximab in Children with Steroid-Dependent Nephrotic Syndrome

Alterations of immune cell subsets in relapsed, thymoma-associated minimal change disease: A case report

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