Staining for and was negative. Idiopathic multicentric castleman disease, Nephrotic syndrome, Tocilizumab Introduction Castleman disease (CD) is a polyclonal non-neoplastic lymphoproliferative disease that was first reported by Dr. Benjamin Castleman in 1956 . CD is classified in accordance with the pathological and clinical manifestations. CD is pathologically classified as the hyaline vascular type or the plasma cell type . CD is clinically classified as unicentric CD in which the lesion is localized in only one region, and multicentric CD (MCD) in which the lesions are present in multiple regions and the patient has prominent clinical symptoms. MCD is divided into three forms: Kaposi’s sarcoma-associated herpesvirus (KSH)/human herpesvirus 8 (HHV-8)-positive MCD, idiopathic MCD (iMCD), and MCD with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome . The pathogenesis of CD remains unclear, but interleukin (IL)-6 plays an important role in the pathological mechanism, and the symptoms and pathology can be explained by overproduction of IL-6 . In Western countries, HHV-8 is frequently associated with the ADX88178 pathogenesis of MCD, especially in human immunodeficiency virus (HIV)-positive individuals. In contrast, Japanese MCD cases are very rare with HHV-8 . The clinical symptoms of MCD include lymphadenopathy, anemia, splenomegaly, renal dysfunction, ADX88178 fever, etc. . The pathological types of renal complications are heterogeneous. The renal complications of MCD are reportedly associated with a poor prognosis . The treatment algorithm of iMCD was reported by the Castleman Disease Collaborative Network. Tocilizumab and glucocorticoid are recommended for the treatment of iMCD, irrespective of severity . Tocilizumab is a humanized anti-human IL-6 receptor monoclonal antibody that blocks the activity of IL-6, thus treating the symptoms and biochemical abnormalities in patients with CD . To our knowledge, there are only two case reports of a patient with CD with nephrotic syndrome who was treated with tocilizumab ADX88178 [9,10]. Herein, we report two cases in which tocilizumab treatment was effective for the treatment of iMCD with nephrotic syndrome. Case reports Case 1 A 58-year-old Japanese man was admitted to our hospital for treatment of nephrotic syndrome. Hematuria had been detected at the age of 42?years, and hematuria and proteinuria (2?+) had been detected at the age of 48?years. At the age of 51?years, the patient had been diagnosed with MCD based on his systemic manifestations, systemic lymphadenopathy, hypergammaglobulinemia, and the pathological findings of a lymph node biopsy. He was diagnosed with plasma cell type iMCD on the basis of systemic manifestations and biopsy findings (Fig.?1a). Open in a separate window Fig. 1 a Histological view of the neck lymph node biopsy in case 1 (HE stain). There is widening of the interfollicular region and atrophy of the germinal center (?40 magnification). A Mouse monoclonal to Tag100. Wellcharacterized antibodies against shortsequence epitope Tags are common in the study of protein expression in several different expression systems. Tag100 Tag is an epitope Tag composed of a 12residue peptide, EETARFQPGYRS, derived from the Ctermini of mammalian MAPK/ERK kinases. prominent increase and infiltration of plasma cells is seen in the interfollicular region (inset??200 magnification). b, c Histological examination of a renal biopsy in case 1. b Diffuse capillary wall thickening with endocapillary hypercellularity and cellular crescent are seen. PAS stain,??400 magnification. c There are vacuolated appearance and focal spike formation in the glomerular basement membrane. PAM stain,??1000 magnification. d There is a moderate chronic tubulointerstitial damage with focal ADX88178 interstitial cellular infiltration. PAS stain,??400 magnification The patient had been monitored without therapy because he was clinically asymptomatic. His serum creatinine (s-Cr) increased from 0.74?mg/dl at the age of 51?years to 1 1.0?mg/dL at the age of 58?years. His blood pressure was 141/75?mmHg. He had bilateral axial and inguinal superficial lymphadenopathy with no tenderness and good mobility. Chest radiography showed bilateral hilar adenopathy. His electrocardiogram was normal. Computed tomography (CT) of the region from the neck to the pelvis showed systemic lymphadenopathy, multiple pulmonary infiltrative shadows, splenomegaly, and hepatomegaly. Laboratory findings are shown in Table ?Table1.1. Renal biopsy revealed that seven of 21 glomeruli showed global sclerosis. The remaining glomeruli revealed ADX88178 diffuse capillary wall thickening with focal segmental endocapillary hypercellularity and four active crescents (cellular and fibrocellular) (Fig.?1b). Periodic acid methenamine silver stain (PAM stain) revealed diffuse vacuolated appearance and focal spike formation of glomerular basement membrane (Fig.?1c). Chronic tubulointerstitial damage with interstitial cellular infiltration was noticed (Fig.?1d). Immunofluorescence microscopy showed diffuse peripheral granular deposits of IgG (Fig.?2a). IgG subclass analysis revealed predominant deposition of IgG1 and IgG2 (Fig.?2b, c), while IgG3 and IgG4 were not detected (Fig.?2d, e). PLA2R was focally weakly positive too (Fig.?2f). Electron microscopy included only glomeruli with global sclerosis. Other causes of secondary membranous nephropathy such as infection, malignancy, autoimmune disease, and potential drugs were ruled out. Table 1 Laboratory findings at start of treatment thead th align=”left” rowspan=”1″ colspan=”1″ Urinalysis /th th align=”left” rowspan=”1″ colspan=”1″ /th th align=”left” rowspan=”1″ colspan=”1″ Blood Chemistry /th th align=”left” rowspan=”1″ colspan=”1″ /th th align=”left” rowspan=”1″ colspan=”1″ Serological test /th th align=”left” rowspan=”1″ colspan=”1″ /th /thead Gravity1.020Total protein8.7?g/dlImmunoglobulin G4156?mg/dLpH6.0Albumin2.1?g/dlImmunoglobulin A512?mg/dLProtein3?+?Asparatate aminotransferase11?IU/LImmunoglobulin M227?mg/dL4.4?g/gCrAlanine aminotransferase7?IU/LComplement activity69?U/mLOccult blood1?+?Lactate dehydrogenase99?IU/LC3 component104?mg/dLGlucose-Total cholesterol115?mg/dLC4 component23?mg/dLKetone-LDL-Cholesterol72?mg/dLAntinuclear antibody160Triglycerides70?mg/dLanti.