Fatal disseminated enterovirus infection in a patient with follicular lymphoma undergoing obinutuzumab maintenance therapy

Follicular lymphoma is the most common subtype of the indolent non‐Hodgkin lymphomas. Treatment usually consists of immuno‐chemotherapy and results in long‐lasting remissions in most cases. Progression‐free survival with the second‐generation anti‐CD20 antibody obinutuzumab was shown to be better than with rituximab when given in combination with either bendamustine or anthracycline‐based chemotherapy. Although treatment is generally well tolerated without an excessive rate of toxicities, there appear to be slightly more adverse events with obinutuzumab than with rituximab. Here, we report the case of a 45‐year‐old female patient that was diagnosed with a disseminated enterovirus infection while undergoing maintenance therapy with obinutuzumab after induction treatment with the combination of bendamustine and rituximab. Enterovirus RNA was detected in the blood, the cerebrospinal fluid, and the colon. A therapy with intravenous immunoglobulins was initiated since the patient presented with a severe treatment‐related immunosuppression indicated by hypogammaglobulinemia. Nonetheless, she eventually died from the enterovirus infection without evidence of lymphoma progression. This case underscores that clinicians should be aware of rare but potentially fatal infectious complications related to treatment protocols containing anti‐CD20 antibodies.     

狭鳕鱼皮胶原多肽对去势大鼠骨微结构影响的研究

目的通过观察狭鳕鱼皮胶原多肽对去势大鼠骨质疏松模型骨微结构的影响，探讨其防治骨质疏松的可行性。方法成年 Wistar 雌性大鼠 60 只，体质量（250±10）g，随机分为 5 组（n=12），分别为正常对照组（A 组）、骨质疏松模型组（B 组）、骨质疏松模型+狭鳕鱼皮胶原多肽预防组（C 组）、骨质疏松模型+狭鳕鱼皮胶原多肽低剂量治疗组（D 组）、骨质疏松模型+狭鳕鱼皮胶原多肽高剂量治疗组（E 组），每组 12 只。B、C、D、E 组采用摘除双侧卵巢法制备大鼠骨质疏松模型。C 组从术前 4 周开始、D、E 组从术后 6 周开始，每天按照 1.0、0.5、1.0 g/kg 行狭鳕鱼皮胶原多肽灌胃，连续 6 周；A、B 组于术后同时间点给予等体积生理盐水灌胃。末次给药 24 h 后，A、B 组大鼠摄股骨 X 线片并测定灰度值；然后颈椎脱臼法处死各组大鼠，取左侧胫骨近端骨组织行 HE 染色，观察骨组织病理学改变，测量骨小梁数量（trabecular number，TN）、平均骨小梁厚度（mean trabecular plate thickness，MTPT）、平均骨小梁间距（mean trabecular plate spacing，MTPS）、骨小梁体积百分比（trabecular bone volume，TBV）、平均骨皮质厚度（mean bone cortical thickness，MBCT）；免疫组织化学染色观测降钙素受体（caltitonin receptor，CTR）及 IL-1 表达水平。 结果B 组大鼠股骨灰度值显著低于 A 组（t=45.130，P=0.000），表明去势大鼠骨质疏松模型制备成功。组织学观察示，A、C、E 组 TN、MTPS、TBV、MBCT 与 B 组比较，差异有统计学意义（P<0.05）；C 组各骨组织形态计量学参数与 D、E 组比较，差异均有统计学意义（P<0.05）；D 组 TN、MTPS、TBV、MBCT 与 A 组比较差异有统计学意义（P<0.05）；E 组仅 MTPS 与 A 组比较差异有统计学意义（P<0.05）；E 组 MTPS、TBV、MBCT 与 D 组比较，差异有统计学意义（P<0.05）。免疫组织化学染色观察示，A、C、D、E 组 CTR、IL-1 表达水平较 B 组降低，C、E 组低于 D 组，差异有统计学意义（P<0.05）；其余组间比较差异均无统计学意义（P>0.05）。 结论狭鳕鱼皮胶原多肽能够改善骨质疏松大鼠的骨微结构，其机制可能与抑制骨组织中 CTR、IL-1 表达有关，但尚未发现其对骨质疏松症有预防作用。     

The P450 enzyme Shade mediates the hydroxylation of ecdysone to 20‐hydroxyecdysone in the Colorado potato beetle,Leptinotarsa decemlineata

Ecdysone 20‐monooxygenase (E20MO), a cytochrome P450 monooxygenase (CYP314A1), catalyses the conversion of ecdysone (E) to 20‐hydroxyecdysone (20E). We report here the cloning and characterization of the Halloween gene Shade (Shd) encoding E20MO in the Colorado potato beetle, Leptinotarsa decemlineata. LdSHD has five conserved motifs typical of insect P450s, ie the Helix‐C, Helix‐I, Helix‐K, PxxFxPE/DRF (PERF) and heme‐binding motifs. LdShd was expressed in developing eggs, the first to fourth instars, wandering larvae, pupae and adults, with statistically significant fluctuations. Its mRNA was ubiquitously distributed in the head, thorax and abdomen. The recombinant LdSHD protein expressed in Spodoptera frugiperda 9 (Sf9) cells catalysed the conversion of E to 20E. Dietary introduction of double‐stranded RNA (dsRNA) of LdShd into the second instar larvae successfully knocked down the LdShd expression level, decreased the mRNA level of the ecdysone receptor (LdEcR) gene, caused larval lethality, delayed development and affected pupation. Moreover, ingestion of LdShd‐dsRNA by the fourth instars also down‐regulated LdShd and LdEcR expression, reduced the 20E titre, and negatively influenced pupation. Introduction of 20E and a nonsteroidal ecdysteroid agonist halofenozide into the LdShd‐dsRNA‐ingested second instars, and of halofenozide into the LdShd‐dsRNA‐ingested fourth instars almost completely relieved the negative effects on larval performance. Thus, LdSHD functions to regulate metamorphotic processes by converting E to 20E in a coleopteran insect species Le. decemlineata.     

Circulating CCL20: A potential biomarker for active vitiligo together with the number of Th1/17 cells

Background

Vitiligo is an autoimmune disease with varying pathological features. Activation of the CCL20-CCR6 axis plays an important role in chronic inflammatory diseases. However, whether CCL20-CCR6 and Th1/17 cells are indicative of active vitiligo is unclear.

CD20 monoclonal antibodies for the treatment of multiple sclerosis: up-to-date

Introduction: Featuring demyelination and axonal degeneration, multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system representing a prominent cause of disability in young adults. The recently established therapeutic targeting of B cells in MS patients using CD20 monoclonal antibodies (CD20-mAbs) not only profoundly suppresses inflammatory disease activity but also materializes as the first treatment approach against disability accumulation in a subset of patients with primary progressive MS.

Areas covered: We will review current concepts regarding the immunopathology of B cells as well as results of clinical trials with CD20-mAbs in MS, from the murine-human chimeras rituximab and ublituximab to their increasingly humanized counterparts ocrelizumab and ofatumumab. We conducted a literature search using PubMed, clinicaltrials.gov, and clinicaltrialsregister.eu. We will focus on studies emphasizing the effectiveness of these mAbs in reducing MS disease activity and progression, long-term safety, optimal dosage and maintenance regimens. Lastly, we will turn to outstanding questions regarding anti-CD20 therapy in MS.

Expert opinion: CD20-mAbs could become first-line drugs in selected patients with highly active MS and already constitute an option for PPMS. Future studies could evaluate whether administration regimens currently in use can be optimized, while registry data could shed light on risk versus benefits on the long run, considering immunosenescence and a potentially increased risk of malignancies and infections in an aging population.