Treatment of thalassaemia: a review of the new approaches on transfusion safety and the novel therapeutics

Lifetime red cell concentrate (RCC) transfusions still account for significant iron overload‐related morbidity and mortality despite chelation therapy in thalassaemia. The cumulative risk of transfusion‐transmitted infections is substantial for thalassaemia patients. Pathogen reduction technologies for RCC may imply a proactive approach against new/re‐emerging pathogens and may be an ultimate safeguard for transfusion safety in the developing countries. Red cell alloimmunization may become a significant clinical challenge in thalassaemia. The availability of high‐throughput molecular blood group antigen typing in the donors may allow perfect match transfusion, beyond ABO‐D and CEK antigen‐matched transfusions. Allogeneic stem cell transplantation (A‐SCT) is the only available curative therapy in thalassaemia, but carries a substantial risk of serious adverse events and mortality. Gene addition therapy for correction of the α‐globin chain imbalance overcomes the problems of donor availability and immunological complications of A‐SCT. Gene editing by either gene disruption or correction emerged as a potential alternative to gene addition therapy in beta‐thalassaemia. A new era of novel therapeutics targeting α/β imbalance, ineffective erythropoiesis or iron dysregulation is unfolding in thalassaemia management, and a number of those now have agents in preclinical and clinical development. Hydroxyurea (HU) may improve globin chain imbalance and be beneficial for reducing or omitting transfusion requirement. Ruxolitinib has allowed steady decrease in spleen volume that may serve for avoiding splenectomy in beta‐thalassaemia. Luspatercept may restore normal erythroid differentiation and improve anaemia. Hepcidin mimetics or TMPRSS6 inhibitors may modulate ineffective erythropoiesis by iron restriction and improve anaemia and organ iron loading.     

Searching for Serum Antibodies to Neuronal Proteins in Patients With Myalgic Encephalopathy/Chronic Fatigue Syndrome

PurposeA role for the immune system in causing myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) is long suspected, but few studies have looked for specific autoantibodies that might contribute to the symptoms. Our aim was to look for evidence of antibodies to neuronal proteins in patients with ME/CSF.MethodsSera samples from 50 patients and 50 healthy individuals were sent coded to the Neuroimmunology Laboratory in Oxford. Screening for antibody binding to neuronal tissue was performed on brain tissue and neuronal cultures. Specific serum antibodies were assessed by antigen-specific cell-based assays and radioimmunoassays. After antibody testing, the associations between seropositive status and clinical data were investigated.FindingsOverall, 8 patients and 11 participants were found to have some serum immunoreactivity toward neuronal or neuromuscular junction proteins, but only 1 patient and 2 participants had specific serum antibodies. Nevertheless, seropositive status in patients with ME was associated with shorter duration since onset and a more severe disease.ImplicationsThe results indicate no overall increased frequency of antibodies to neuronal proteins in ME/CSF and no evidence of a specific antibody that might be causative or contribute to clinical features in patients. However, the association of seropositive status with shorter duration of disease and more severe symptoms suggests a possible role of antibodies at onset in some patients and should be the focus of future studies.     

Discovering novel lung cancer associated antigens and the utilization of their autoantibodies in detection of lung cancer

ObjectiveThe identification of tumor-associated antigens (TAAs) and their corresponding autoantibodies in lung cancer (LC) may expand our vision of cancer immunity. This study aims to screen novel TAAs to distinguish LC from the healthy population.MethodsIn our previous study, 35 genes encoding LC-associated TAAs were identified from the serological analysis of recombinant cDNA expression libraries (SEREX), and Oncomine database was further used to identify potential genes in cancer progression. Autoantibody to TAAs were tested by enzyme-linked immunosorbent assay (ELISA) in sera from 1379 participants in validation set and verification set.FindingsBased on analysis of three independent microarrays in Oncomine, ten genes were consistently dysregulated in LC. The sera level and positive frequency of the anti-TOP2A, anti-ACTR3, anti-RPS6KA5 and anti-PSIP1 from LC patients were higher than normal control in validation set. The area under curve (AUC) of anti-TOP2A, anti-ACTR3, anti-RPS6KA5 and anti-PSIP1 was respectively 0.758, 0.787, 0.707, 0.668. The sensitivity of these four autoantibodies for LC detection ranged from 26.63 % to 32.07 % with the specificity over 90 %. Data from the verification set confirmed the results. Except that, the frequency of serum autoantibody against TOP2A (43.3 %) and ACTR3 (50.0 %) was significantly higher in early stage LC than late stage (23.6 % and 22.3 %, respectively).ConclusionTOP2A, ACTR3, RPS6KA5 and PSIP1 can elicit humoral immune response in LC and their autoantibodies have relationship with the tumorigenesis of LC. Anti-TOP2A and anti-ACTR3 have the potential to serve as a serological biomarkers in early stage LC.     

HLA markers in familial Lichen Sclerosus

Background: Lichen sclerosus (LS) has been identified with increased frequency in families,often associated with HLA markers, mainly DQ7. A genetic co‐etiology seems likely in this setting. Moreover, there is an association of LS with autoimmune disorders, such as the presence of anti‐thyroid peroxidase autoantibodies (anti‐TPO), a hallmark of autoimmune thyroid diseases. Patients and Methods: In 3 families affected by LS, we verified their HLA markers, and identified previously undiagnosed cases of LS and autoimmune disorders. 30 individuals were examined with history, skin biopsy, HLA class I and II typing by PCR‐SSP, and measurement of anti‐TPO, free thyroxine and thyroidstimulating hormones (TSH) levels. Results: There were 8 cases of LS, 50 % of them anti‐TPO+. Autoimmune disorders were found in 40 % (total) and in 87.5 % of those affected. Most common HLA markers were B*15, B*57, CW*03, CW*07, CW*18, DRB1*04, DRB1*07, DRB4*. The three latter have been previously associated with LS. Conclusion: New cases of LS and autoimmune disorders can be detected in first degree relatives of patients with LS. The presence of anti‐TPO antibodies strongly suggests autoimmune thyroiditis. There is intra‐familial association between the haplotype HLA‐B*15 ‐DRB1*04 ‐DRB4* and anti‐TPO,emphasizing their link with thyroiditis. New familial approaches might help to make clear the pathogenesis of LS and its association with autoimmune diseases.     

日本血吸虫成虫67kD蛋白的分离与鉴定

目的 :分离日本血吸虫感染及免疫血清识别的成虫抗原 (AWA)中的特异蛋白带 ,为血吸虫病免疫诊断提供新的抗原分子。方法 :免疫印迹法分析AWA的特异蛋白带 ,电泳层析法分离靶抗原。结果 :获得了感染血清和免疫血清识别的 6 7kD蛋白。结论 :电泳层析法是一种分离血吸虫抗原的有效方法     

慢性乙型肝炎中可溶性白细胞介素2受体与其它血清学指标的关系

目的 :探讨血清可溶性白细胞介素 2受体 (sIL 2R)在慢性乙型病毒性肝炎 (慢乙肝 )中的发病机制及sIL 2R与肝纤维化指标、肝功能的相关关系。方法 :对 312例肝活检病人按组织病理学炎症和纤维化程度进行分级分期 ,同时检测了病人血清sIL 2R、肝功能及肝纤维化相关指标。结果 :血清sIL 2R均值较对照组明显增高 (P <0 .0 1) ,增幅随着肝脏病理炎症和纤维化程度的加重而逐渐加大 ,各组间比较差异有显著性 (P <0 .0 5或P <0 .0 1)。sIL 2R与血清白蛋白 (A)呈显著负相关 ,与血清脯氨酸肽酶 (PLD)、Ⅳ型胶原 (CⅣ )、层粘连蛋白 (LN)、透明质酸 (HA)、Ⅲ型前胶原氨基端肽 (PⅢNP)、肝功指标中的TB、DB、G、ALT、AST、AKP、γ GT呈显著正相关 (P <0 .0 5或P <0 .0 1)。结论 :慢乙肝病人血清sIL 2R水平与A呈显著负相关 ,与PLD、CⅣ、LN、HA、PⅢNP呈显著正相关 ;sIL 2R的血清水平能反映肝脏组织学病变的程度 ,可作为判断肝组织炎症和纤维化程度的参考指标。     

儿童慢性乙型肝炎细胞免疫功能及胸腺素疗效

目的　探讨慢性乙型肝炎(CHB)患儿细胞免疫功能及胸腺素疗效。方法　6 0例CHB患儿随机分为常规组(予常规治疗)和胸腺素组(在常规治疗基础上+胸腺素) ,并以6 0例健康儿童作为正常对照组。于治疗前、疗程结束后1mo检测T细胞亚群(CD+ 3 、CD+ 4 、CD+ 8)、血清白细胞介素2 (IL 2 )及可溶性白细胞介素2受体(sIL 2R)水平;定期复查肝功能、乙肝标志物和HBV DNA。结果　与正常对照组比较,CHB组CD+ 3 与CD+ 4 的百分率、CD+ 4 /CD+ 8及血清IL 2水平明显降低(P均<0 0 1) ,CD+ 8百分率及血清sIL 2R水平明显升高(P均<0 0 1) ;与常规组比较,胸腺素组血清ALT明显下降(P <0 0 1) ,ALT复常时间明显缩短(P <0 0 1) ,HBeAg转阴率明显上升(P <0 0 5 ) ,各免疫学指标明显恢复,差异均有统计学意义(P <0 0 1或P <0 0 5 )。结论　CHB患儿细胞免疫功能低下,胸腺素能增强细胞免疫功能,有利于病毒清除和肝功能的恢复     

可溶性细胞间黏附分子-1在急性肝内胆汁淤积兔模型中的表达

目的探讨可溶性细胞间黏附分子(sICAM-1)在急性肝内胆汁淤积兔模型中的表达及其意义。方法39只健康的新生大耳白兔随机分成4组:3个实验组(n=9)和1个空白对照组(n=12)。每个实验组分别为3个时间点处理组(24、48、72 h)。实验组采用1次灌服α-荼异硫氰酸盐(ANIT)200 mg/kg方法造成急性肝内胆汁淤积。按时分批取标本,检测其血清和胆汁中sICAM-1水平。结果实验组血清、胆汁中sICAM-1各时间点水平明显高于正常对照组(P均<0.05),其中48 h>72 h>24 h。结论sICAM-1在胆汁淤积中表达升高,与肝脏损伤程度和病程相关。