Immune thrombocytopenia (ITP) is an autoimmune disease defined by low platelet counts which presents with an increased bleeding risk. Several genetic risk factors (e.g., polymorphisms in immunity-related genes) predispose to ITP. Autoantibodies and cytotoxic CD8(+) T cells (Tc) mediate the anti-platelet response leading to thrombocytopenia. Both effector arms enhance platelet clearance through phagocytosis by splenic macrophages or dendritic cells and by induction of apoptosis. Meanwhile, platelet production is inhibited by CD8(+) Tc targeting megakaryocytes in the bone marrow. CD4(+) T helper cells are important for B cell differentiation into autoantibody secreting plasma cells. Regulatory Tc are essential to secure immune tolerance, and reduced levels have been implicated in the development of ITP. Both Fc gamma-receptor-dependent and -independent pathways are involved in the etiology of ITP. In this review, we present a simplified model for the pathogenesis of ITP, in which exposure of platelet surface antigens and a loss of tolerance are required for development of chronic anti-platelet responses. We also suggest that infections may comprise an important trigger for the development of auto-immunity against platelets in ITP. Post-translational modification of autoantigens has been firmly implicated in the development of autoimmune disorders like rheumatoid arthritis and type 1 diabetes. Based on these findings, we propose that post-translational modifications of platelet antigens may also contribute to the pathogenesis of ITP.

目的 探究免疫性血小板减少性紫癜（ITP）患儿外周血Th1、Th2、Th17、Treg细胞表达水平及对临床的指导意义。方法 选取2017年6月~2018年9月于我院诊断并治疗的ITP患儿46例为病例组,以同期门诊行健康检查儿童40例为对照组。采用流式细胞术检测外周血单个核细胞中Th1、Th17、Th2、Treg细胞表达水平,采用酶联免疫方法对细胞因子IFN-γ、IL-4、IL-17检测,分析ITP患儿Th1、Th17、Th2、Treg细胞比例、细胞因子和疾病不同时期及血小板水平的关系。结果 病例组患儿外周血Th1细胞、Treg细胞频数比例、IFN-γ、IL-17水平低于对照组,Th2、Th17细胞比例、IL-4水平高于对照组,差异有统计学意义（P<0.05）。病例组治疗后患儿外周血Th1、Treg水平、血小板计数及细胞因子IL-4较治疗前升高,Th2、Th17水平及细胞因子IFN-γ、IL-17较治疗前降低,差异有统计学意义（P<0.05）。治疗前后血小板变化与外周血Treg、Th1水平呈正相关关系（r=0.461,0.383）,与Th17、Th2水平呈负相关关系（r= -0.362,-0.311）。结论 本次研究表明外周血Th1、Th2、Th17、Treg细胞及细胞因子比例失衡与儿童ITP发病有关,通过测定外周血各类T淋巴细胞可初步判断疾病状态及血小板水平。

A prospective, population-based registration of children with immune thrombocytopenic purpura (ITP) was performed in Norway in 1996 and 1997. Ninety-two cases were identified, indicating an incidence of 5.3 per 100,000 children under 15 years. The sex ratio (female/male) was 1.2/1. Fifty-six percent presented with cutaneous signs only. The lowest platelet count was < 20 x 10(9)/L in 91%. In spite of mild bleeding symptoms, medical treatment was given in 68%, in most cases (57/63) with intravenous immunoglobulin. A total of 41/44 patients with platelet counts of < or = 5 x 10(9)/L were treated, regardless of whether they had mucous bleedings or not. Eighteen percent had platelet counts < 150 x 10(9)/L at 6 months, and 9% at 12 months following diagnosis. One patient with therapy-resistant chronic ITP died 16 months after diagnosis from an anesthesia complication related to profound epistaxis. This study shows a relatively high incidence. As in other studies, there was a tendency to treat platelet counts rather than bleeding symptoms.

To investigate the levels of NK cells and their relevant cytokines (IL-10, TGF-β and IFN-γ) in patients with primary immune thrombocytopenia (ITP). All samples were obtained from 42 patients (22 newly diagnosed and 20 in remission) and 20 healthy volunteers. The levels of IL-10 and IFN-γ in blood serum were detected by enzyme-linked immunosorbent assay (ELISA). The percentage of CD3(-) CD56(+) NK cell, CD3(-) CD56(bright) CD16(-) NK cell, CD3(-) CD56(dim) CD16(+) NK cell in peripheral blood lymphocyte were detected by flow cytometry. The NK cells were isolated by immunomagnetic microbeads. The mRNA expression levels of IL-10, TGF-β, and IFN-γ in NK cells were detected by real-time fluorescent quantitative PCR. Correlation between the above measured results was analyzed. ① The blood serum level of IFN-γ in newly diagnosed ITP patients [ (653.0±221.6) ng/L] was higher than that in remission ITP patients [ (484.4±219.5) ng/L] and healthy control [ (390.9±253.5) ng/L] (=0.022, =0.001). The blood serum level of IL-10 in newly diagnosed ITP patients was lower than that in healthy control [ (52.09±26.66) ng/L (79.44±38.43) ng/L, =0.007]. ②The percentage of NK cell in newly diagnosed and remission ITP patients [ (9.53±3.93) %, (9.03±3.78) %] were significantly lower than that in healthy control [ (13.72±7.42) %] (=0.013, =0.007). The ratio of CD3(-) CD56(bright) CD16(-) NK cell/total NK cells in newly diagnosed ITP patients was higher than that in healthy control [ (6.85±4.43) % (4.05±2.81) %, =0.032]. The ratio of CD3(-)CD56(dim) CD16(-) NK cell/total NK cells in newly diagnosed ITP patients was lower than that in healthy control [ (93.14±4.43) % (95.94±2.81) %, =0.032]. ③ There was no significant difference in the mRNA expression level of IFN-γ in NK cells of ITP patients and healthy control (all >0.05). The mRNA expression levels of IL-10 and TGF-β in NK cells in newly diagnosed ITP patients were significantly higher than that in healthy control (1.82±1.32 1.02±1.03, =0.023; 2.80±2.31 1.46±1.37, =0.028). The ratio of CD3(-)CD56(bright) CD16(-) NK cell/total NK cells was positively correlated with the mRNA expression levels of IL-10, TGF-β in NK cells (=0.424, =0.001; =0.432, <0.001). NK cells may compensate for the deficiency of the number by enhancing the secretion of negative regulation cytokines, acting as "protective" roles in the disease.