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

Abstract

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....

Concurrent renal amyloidosis and thymoma resulting in a fatal ventricular thrombus in a dog

“…Autoreactive T cell clones escaping negative selection in the abnormal thymic tissue or suppression of regulatory T‐cells controlling self‐tolerance are likely integral in development of thymoma‐associated autoimmune disease and may have contributed to serum AA production in this case . Minimal change disease, a glomerulopathy associated with nephrotic syndrome, was described in an older woman with recurrent thymoma . Interestingly, when her thymoma was treated and her proteinuria decreased, her Th17/regulatory T cell ratio decreased .…”

“…6,15 Minimal change disease, a glomerulopathy associated with nephrotic syndrome, was described in an older woman with recurrent thymoma. 16 Interestingly, when her thymoma was treated and her proteinuria decreased, her Th17/regulatory T cell ratio decreased. 16 We propose that a combination of thymoma associated and immune dysregulation and tumoral inflammation may have resulted in renal amyloid deposition in this dog.…”

“…16 Interestingly, when her thymoma was treated and her proteinuria decreased, her Th17/regulatory T cell ratio decreased. 16 We propose that a combination of thymoma associated and immune dysregulation and tumoral inflammation may have resulted in renal amyloid deposition in this dog. 7 Nephrotic syndrome has been associated with hypercoagulable states and a predisposition for thrombosis in dogs and humans.…”

Nephrotic Syndrome and a Retroperitoneal Mass: A Case Report of a Patient with Recurrent Invasive Thymoma

“…Nevertheless, we feel it is reasonable to consider that abnormalities in the immune system may result from thymoma as well as thymectomy, since the thymus is the primary stromal milieu guiding the maturation and selection of T-lymphocytes ( 15 , 16 ). Interestingly, a detailed description of changes in the immune cell subset composition in recurrent thymoma-associated MCD was recently published ( 17 ), implying the presence of immunologic disturbance in subjects with recurrent disease. However, whether or not different histological types of thymoma result in distinct paraneoplastic glomerular injuries remains unclear.…”

Lupus Nephritis with Thymoma Managed by Thoracoscopic Surgery and Prednisolone

“…On the other hand, the effect of chemotherapy in patients with relapsed thymoma was investigated based on the measurement of the T cell subsets in a patient with minimal change disease (MCD) ( 16 ). The study found that Th17 cells decreased and that proteinuria resolved after chemotherapy.…”