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Rituximab resistance

Shin Nagai, Junji Hiraga, Noriyuki Suzuki, Naruko Suzuki, Yusuke Takagi, Michihiko Narita, Yoshitoyo Kagami
We report a rare case of composite lymphoma comprising extranodal NK/T-cell lymphoma, nasal type, (ENKL) and diffuse large B-cell lymphoma (DLBCL) in a 70-year-old man complaining of fatigue. Computed tomography showed multiple consolidations in both lungs, and ENKL was diagnosed from transbronchial lung biopsy. Positron emission tomography also detected abnormal uptake in the stomach, and DLBCL was diagnosed from subsequent gastroscopy. Two courses of chemotherapy including rituximab achieved reduction in DLBCL, but ENKL proved resistant to this treatment and progressed...
2018: Case Reports in Hematology
Magdalena Kraft, Margitta Worm
Pemphigus foliaceus is an autoimmune skin disease mediated by autoantibodies directed against desmoglein-1 located in the upper epidermal layer. Rituximab, a monoclonal anit-CD20 antibody depleting b-cells, offers an effective treatment possibility for therapy-resistant pemphigus foliaceus. Here, we present the case of 55-year-old man who did not respond sufficiently to conventional treatment with prednisolone, azathioprine, and cyclophosphamide, but underwent almost complete remission after rituximab treatment...
2018: Frontiers in Medicine
Maho Nakazawa, Katsuya Suzuki, Hidekata Yasuoka, Kunihiro Yamaoka, Tsutomu Takeuchi
Background: In granulomatosis with polyangiitis (GPA), peripheral nerve involvement is common but central nervous system (CNS) involvement is extremely rare and treatment strategy has not been established. We report a case of intravenous cyclophosphamide (IVCY)-resistant GPA with associated cranial neuropathies that was successfully treated with rituximab (RTX). Case presentation: A 37-year-old man with intractable sinusitis had several months of headache, hoarseness, and dysphagia; a month of right-sided deafness and nasal bleeding; and a week of dysarthria, steppage gait, and numbness in the right L5 distribution...
2018: Inflammation and Regeneration
Daniel Bojar, Tobias Fuhrer, Martin Fussenegger
Capitalizing on the ability of mammalian cells to conduct complex post-translational modifications, most protein therapeutics are currently produced in cell culture systems. Addition of a signal peptide to the product protein enables its accumulation in the cell culture supernatant, but separation of the product from endogenously secreted proteins remains costly and labor-intensive. We considered that global downregulation of translation of non-product proteins would be an efficient strategy to minimize downstream processing requirements...
November 20, 2018: Metabolic Engineering
Marcel Nijland, Annika Seitz, Martijn Terpstra, Gustaaf W van Imhoff, Philip M Kluin, Tom van Meerten, Çiğdem Atayar, Léon C van Kempen, Arjan Diepstra, Klaas Kok, Anke van den Berg
Current genomic models in diffuse large B-cell lymphoma (DLBCL) are based on single tumor biopsies, which might underestimate heterogeneity. Data on mutational evolution largely remains unknown. An exploratory study using whole exome sequencing on paired (primary and relapse) formalin fixed paraffin embedded DLBCL biopsies ( n = 14) of 6 patients was performed to globally assess the mutational evolution and to identify gene mutations specific for relapse samples from patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone...
November 20, 2018: Cancers
C Addy, G Doran, A L Jones, G Wright, S Caskey, D G Downey
BACKGROUND: Non-Tuberculous Mycobacterial-pulmonary disease (NTM-PD) is increasing in incidence and prevalence. Mycobacterium abscessus (M.abscessus) is a rapid growing multi-resistant NTM associated with severe NTM-PD requiring prolonged antibiotic therapy. Complications of therapy are common but reports on direct complications of active NTM-PD are rare. Vasculitis has been described as a rare complication of NTM-PD, most often in individuals with inherited immune defects. This case is the first to describe an ANCA positive vasculitide (Microscopic Polyangiitis) secondary to M...
November 19, 2018: BMC Pulmonary Medicine
Yo Han Ahn, Seong Heon Kim, Kyoung Hee Han, Hyun Jin Choi, Heeyeon Cho, Jung Won Lee, Jae Il Shin, Min Hyun Cho, Joo Hoon Lee, Young Seo Park, Il-Soo Ha, Hae Il Cheong, Su Young Kim, Seung Joo Lee, Hee Gyung Kang
BACKGROUND: The anti-CD20 monoclonal antibody rituximab (RTX) has been proposed as a rescue therapy for difficult-to-treat nephrotic syndrome (NS). We conducted a clinical trial to evaluate the efficacy and safety of RTX in children with difficult-to-treat NS dependent on or resistant to steroids and calcineurin inhibitors (CNIs). METHODS: A multicenter open-label trial was performed at 8 major pediatric nephrology centers in Korea. The investigation consisted of a randomized controlled trial for steroid- and CNI-dependent NS (DDNS; randomization into the RTX group and the control group, at a ratio of 2:1) and a single-arm study of steroid and CNI-resistant NS (DRNS)...
November 2018: Medicine (Baltimore)
Shuichiro Fujinaga, Tomohiko Nishino, Chisato Umeda, Yuji Tomii, Yoshitaka Watanabe, Koji Sakuraya
BACKGROUND: Although rituximab (RTX) may be effective treatment in children with nephrotic syndrome who are resistant to cyclosporine A and steroid (CsA-SRNS), long-term outcomes after B cell depleting therapy remain unclear. CASE-DIAGNOSIS/TREATMENT: We retrospectively reviewed the clinical courses (median follow-up, 5.1 years) of six CsA-SRNS children (three boys; median age at RTX, 4.2 years) unresponsive to oral cyclosporine combined with ≥ 2 courses of intravenous methylprednisolone pulses, who received RTX within 6 months after disease onset (median 11 weeks)...
November 13, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Katsuyoshi Takata, Ken Saito, Satoshi Maruyama, Tomoko Miyata-Takata, Hidekazu Iioka, Shujiro Okuda, Yiwei Ling, Kennosuke Karube, Yukari Miki, Yoshinobu Maeda, Tadashi Yoshino, Christian Steidl, Eisaku Kondo
Despite receiving rituximab-combined chemotherapy, follicular lymphoma (FL) patients often suffer tumor recurrence, and understand the cause of relapse in FL would thus significantly ameliorate the tumor therapeutics. Here we demonstrate that the TRA-1-60-expressing cells are a unique population in FLs, converge to the conventional stem cell marker Oct3/4 and ALDH1-positive population, and resist current B-lymphoma agents. TRA-1-60 expression was observed only in scattered lymphoma cells in FL tissues as well as resting B-lymphocytes inside germinal centers...
November 11, 2018: Cancer Science
Jiyuan Yang, Lian Li, Jindřich Kopeček
This review highlights a new paradigm in macromolecular nanomedicine - drug-free macromolecular therapeutics (DFMT). The effectiveness of the new system is based on biorecognition events without the participation of low molecular weight drugs. Apoptosis of cells can be initiated by the biorecognition of complementary peptide/oligonucleotide motifs at the cell surface resulting in the crosslinking of slowly internalizing receptors. B-cell CD20 receptors and Non-Hodgkin lymphoma (NHL) were chosen as the first target...
October 12, 2018: Biomaterials
Rita Quelhas da Costa, M Elena Aguirre-Alastuey, David A Isenberg, Amanda M Saracino
Importance: Cutaneous lupus erythematosus (CLE) can be severe and treatment resistant. B-cell depletion therapy (BCDT) with rituximab is well recognized in organ involvement in systemic lupus erythematosus (SLE), but its efficacy in cutaneous manifestations is less well established. Objective: To evaluate the outcomes of BCDT in CLE and its clinical subtypes in the setting of associated SLE. Design, Setting, and Participants: This single-center, retrospective, cohort study was performed at the adult tertiary referral Rheumatology Department of University College London Hospital, London, United Kingdom, from January 1, 2000, through March 31, 2016, with 12-month follow-up completed on March 31, 2017...
October 31, 2018: JAMA Dermatology
Tomoko Horinouchi, Mayumi Sako, Koichi Nakanishi, Kenji Ishikura, Shuichi Ito, Hidefumi Nakamura, Mari Saito Oba, Kandai Nozu, Kazumoto Iijima
BACKGROUND: Idiopathic nephrotic syndrome (INS) is the most common chronic glomerular disease in children. Approximately 80-90% of patients with childhood INS have steroid-sensitive nephrotic syndrome (SSNS), and can obtain remission with steroid therapy, while the remainder have steroid-resistant nephrotic syndrome (SRNS). Furthermore, approximately 50% of children with SSNS develop frequently-relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS). Children with FRNS/SDNS are usually treated with immunosuppressive agents such as cyclosporine, cyclophosphamide, or mizoribine in Japan...
November 1, 2018: BMC Nephrology
Rossella Siligato, Valeria Cernaro, Chiara Nardi, Francesca De Gregorio, Guido Gembillo, Giuseppe Costantino, Giovanni Conti, Michele Buemi, Domenico Santoro
Minimal change disease (MCD) and Focal and segmental glomerulosclerosis (FSGS) are two of the major causes of nephrotic syndrome (NS) in children and adults. According to KDIGO (Kidney Disease: Improving Global Outcomes) guidelines, the treatment of adult primary MCD and FSGS should be based on immunosuppressants and antiproteinuric drugs. Recently, Rituximab, a humanized monoclonal antibody (mAb) has emerged as a potential treatment for steroid or calcineurin inhibitor-dependent patients; it has however demonstrated lower efficacy in those with nephrotic syndrome that is resistant to the above indicated drugs...
November 2018: Expert Opinion on Investigational Drugs
Jacek Zachwieja, Magdalena Silska-Dittmar, Aleksandra Żurowska, Magdalena Drożyńska-Duklas, Lidia Hyla-Klekot, Grażyna Kucharska, Roman Stankiewicz, Ilona Olszak-Szot, Dorota Drożdż, Anna Moczulska, Danuta Zwolińska, Anna Medyńska, Przemyslaw Sikora, Bieniaś Beata, Marcin Tkaczyk, Anna Rogowska-Kalisz, Danuta Ostalska-Nowicka
The aim of the study was a multicenter analysis of the efficacy and safety of a non-standard immunosuppressive therapy with rituximab (Rtx) in children with steroid-resistant nephrotic syndrome (SRNS) with particular emphasis on the possibility of permanent discontinuation or dose reduction of other immunosuppressive drugs such as glucocorticoids and cyclosporine A after 6 months of observation. The study group consisted of 30 children with idiopathic nephrotic syndrome, who were unresponsive to standard immunosuppressive treatment, and hospitalized in the years 2010-2017 in 8 pediatric nephrology centers in Poland...
October 22, 2018: Clinical and Experimental Pharmacology & Physiology
Kjell Tullus, Hazel Webb, Arvind Bagga
More than 85% of children and adolescents (majority between 1-12 years old) with idiopathic nephrotic syndrome show complete remission of proteinuria following daily treatment with corticosteroids. Patients who do not show remission after 4 weeks' treatment with daily prednisolone are considered to have steroid-resistant nephrotic syndrome (SRNS). Renal histology in most patients shows presence of focal segmental glomerulosclerosis, minimal change disease, and (rarely) mesangioproliferative glomerulonephritis...
December 2018: Lancet Child & Adolescent Health
A Ishiwatari, S Wakai, H Shirakawa, K Honda
Primary membranous nephropathy (MN) is an organ-specific autoimmune disease mainly caused by autoantibodies acting against the podocyte antigen M-type phospholipase A2 receptor 1 (PLA2R). Herein we present the clinical and histologic findings, including PLA2R staining, of early recurrent MN after kidney transplantation that was successfully treated with rituximab. A 60-year-old Japanese man had end-stage renal failure due to steroid-resistant primary MN and underwent ABO-incompatible living donor kidney transplantation...
October 2018: Transplantation Proceedings
Yunzi Liu, Yifan Shi, Rong Ren, Jingyuan Xie, Weiming Wang, Nan Chen
Focal segmental glomerulosclerosis (FSGS) is a glomerulonephritis with podocyte injury. The renal prognosis of FSGS is relative poor. The overall remission rate of the FSGS patients with nephrotic syndrome to immunosuppressive treatments was reported as 47-66%, highlighting its therapeutic challenge-lacking in sufficient evidence-based interventions. In first-line treatment of nephrotic syndrome, daily oral prednisolone is a commonly used drug, whereas optimal treatment strategies, like indications and duration, remain controversial...
October 2018: Nephrology
Ekkehard Genth
Idiopathic inflammatory myopathies (IIM) are a rare and clinically polymorphic and heterogenous group of myositis syndromes. Myositis is part of a systemic autoimmune disorder with various extramuscular manifestations affecting skin, lungs, joints, esophagus and other organ systems. Most myositis patients have autoantibodies against non organspecific antigens. More than 20 different autoantibodies are known. They are associated with different clinical phenotypes of adult or juvenile dermatomyositis or myositis-overlap syndromes and different genetic markers...
October 2018: Deutsche Medizinische Wochenschrift
Paolo Fraticelli, Colomba Fischetti, Fausto Salaffi, Marina Carotti, Massimo Mattioli, Giovanni Pomponio, Armando Gabrielli
OBJECTIVES: To describe a single centre experience using combination therapy with rituximab (RTX) and mycophenolate mofetil (MMF) in a prospective series of systemic sclerosis (SSc) patients with pulmonary and cutaneous involvement, rapidly progressive or resistant to conventional therapy. METHODS: RTX was administered in two different regimens (1000 mg fortnightly x 2 or 375 mg/m2/week for 4 consecutive weeks) at baseline and after 6 months, associated with MMF 2000 mg/day continuously...
July 2018: Clinical and Experimental Rheumatology
Manuela Colucci, Rita Carsetti, Simona Cascioli, Jessica Serafinelli, Francesco Emma, Marina Vivarelli
BACKGROUND: A pathogenic role of B cells in non-genetic nephrotic syndrome has been suggested by the efficacy of rituximab, a B cell depleting antibody, in maintaining a prolonged remission. However, little information is available on B cell homeostasis in nephrotic syndrome patients. METHODS: We retrospectively analyzed by flow cytometry the distribution of different B cell subpopulations in 107 steroid-sensitive and in 6 genetic steroid-resistant nephrotic syndrome pediatric patients, compared with age- and sex-matched controls...
January 2019: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
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