Accurate detection of reemergent anti-donor ABO antibody is crucial for safe transfusion in ABO major incompatible HSCT patient after achieved the stages of full switch to donor type

Dynamic monitoring ABO chimera including erythroid ABO antigen and anti-A/B is crucial to not only assess the status of erythroid engraftment but also achieve personalized safety transfusion in patients post ABO incompatible hematopoietic stem cell transplantation. Transfusion support for ABO incompatible (ABOi) HSCT patients after achieved complete alteration to donor origin still remains cautious because the instant hematopoietic status on these transplant patients possibly returned to patient origin derived from early disease relapse and graft loss or failure. We reported that reemergent anti-B in a female patients (donor/patient: B/O) at the early phase after achievement complete donor type were not effectively found from partial automatic ABO blood grouping systems, which directly resulted in differential judgement of transplantation stage for about 15 days and disturbed the optimal recommendation on transfusion support. Meanwhile, the solely alteration of ABO chimera was found and earlier than changes of other markers such as MRD diagnosis, chimerism analysis by STR-PCR and sex chromosome assays, which can be an available predictors for bad transplant outcomes such as graft failure.     

Myelopathy due to human T-cell leukemia virus type-1 from the donor after ABO-incompatible liver transplantation

We report the case of a 53-year-old-man who developed human T-cell leukemia virus type-1-associated myelopathy (HAM) after ABO-incompatible liver transplantation for alcoholic liver cirrhosis. The living donor was seropositive for human T-cell leukemia virus type-1 (HTLV-1) and the recipient was seronegative for HTLV-1 before transplantation. After transplantation, the recipient developed steroid-resistant acute cellular rejection, which was successfully treated using anti-thymocyte globulin, and he was eventually discharged. He underwent spinal surgery twice after the transplantation for the treatment of cervical spondylosis that had been present for a period of 9 months before the transplantation. The surgery improved his gait impairment temporarily. However, his gait impairment progressed, and magnetic resonance imaging revealed multiple sites of myelopathy. He was diagnosed with HAM 16 months after the transplantation. Pulse steroid therapy (1000 mg) was administered over a period of 3 days, and his limb paresis improved. Presently, steroid therapy is being continued, with a plan to eventually taper the dose, and he is being carefully followed up at our institution. Our case suggests that liver transplantation involving an HTLV-1-positive living donor carries the risk of virus transmission and short-term development of HAM after transplantation.     

Genomic and Transcriptomic Landscape of Triple-Negative Breast Cancers: Subtypes and Treatment Strategies

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血清TRAb IgG亚型在甲状腺相关性眼病患者中的特征及临床意义

目的探讨血清TRAb IgG各亚型在不同活动分期甲状腺相关性眼病(thyroid-associated ophthalmopathy,TAO)患者中的分布特点,及其在评估TAO活动度中的价值。方法选取2018年8月至2019年2月郑州大学第一附属医院收治的TAO患者43例,依据临床活动度评分(clinical activity score,CAS)进一步分为活动期组(AP组,CAS≥3分,22例)和静止期组(IP组,CAS<3分,21例);Graves病患者(GD组)30例,桥本甲状腺炎患者(HT组)19例,并以同期健康体检者(NC组)50名作为正常对照。收集各组受试者临床基本资料,化学发光免疫法检测血清FT3、FT4、TSH、甲状腺过氧化物酶抗体(TPOAb)、甲状腺球蛋白抗体(TgAb)、促甲状腺激素受体抗体(TRAb)水平,酶联免疫吸附法检测血清TRAb IgG和IgG各亚型的百分结合率[binding rate in percentage,(B)],比较各亚型的阳性率和阳性亚型的相对含量。结果(1)与HT组相比,TAO组、GD组IgG1、IgG2阳性率降低,差异有统计学意义(P<0.05)。各疾病组间TRAb IgG亚型相对含量无明显差异(P>0.05)。(2)与IP组相比,AP组IgG1(B)、IgG1阳性率显著升高,IgG4(B)、IgG4相对含量显著降低(P<0.05)。(3)IgG1(B)与TAO活动度呈正相关(B=6.190,P=0.007),IgG4(B)越高越倾向于静止期,但差异无统计学意义(B=-16.390,P=0.052)。(4)活动率评估TAO处于活动期的受试者工作特征(ROC)曲线下面积为0.859(95%CI 0.746~0.973,P<0.05),当活动率为4.29时,约登指数最大,其判断敏感度为81.8%,特异度为81.0%。结论在TAO患者中血清TRAb IgG1水平升高提示疾病趋向活动期,IgG4水平升高提示疾病趋向静止期。活动率可为评估TAO是否处于活动期提供参考依据。     

Tumor microenvironment characterization identifies two lung adenocarcinoma subtypes with specific immune and metabolic state

The tumor microenvironment (TME) is a vital component of tumor tissue. Increasing evidence suggests their significance in predicting outcomes and guiding therapies. However, no studies have reported a systematic analysis of the clinicopathologic significance of TME in lung adenocarcinoma (LUAD). Here, we inferred tumor stromal cells in 1184 LUAD patients using computational algorithms based on bulk tumor expression data, and evaluated the clinicopathologic significance of stromal cells. We found LUAD patients showed heterogeneous abundance in stromal cells. Infiltration of stromal cells was influenced by clinicopathologic features, such as age, gender, smoking, and TNM stage. By clustering stromal cells, we identified 2 clinically and molecularly distinct LUAD subtypes with immune active and immune repressed features. The immune active subtype is characterized by repressed metabolism and repressed proliferation of tumor cells, while the immune repressed subtype is characterized by active metabolism and active proliferation of tumor cells. Differentially expressed gene analysis of the two LUAD subtypes identified an immune activation signature. To diagnose TME subtypes practically, we constructed a TME score using principal component analysis based on the immune activation signature. The TME score predicted TME subtypes effectively in 3 independent datasets with areas under the receiver operating characteristic curves of 0.960, 0.812, and 0.819, respectively. In conclusion, we proposed 2 clinically and molecularly distinct LUAD subtypes based on tumor microenvironment that could be valuable in predicting clinical outcome and guiding immunotherapy.