Frydman Galit H, Davis Nick, Beck Paul L, Fox James G
Department of Biological Engineering, Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
The Gastrointestinal Research Group, Division of Gastroenterology, University of Calgary, Calgary, AB, Canada.
Helicobacter. 2015 Aug;20(4):239-51. doi: 10.1111/hel.12200. Epub 2015 Mar 1.
Idiopathic thrombocytopenic purpura (ITP) is typically a diagnosis of exclusion, assigned by clinicians after ruling out other identifiable etiologies. Since a report by Gasbarrini et al. in 1998, an accumulating body of evidence has proposed a pathophysiological link between ITP and chronic Helicobacter pylori (H. pylori) infection. Clinical reports have described a spontaneous resolution of ITP symptoms in about 50% of chronic ITP patients following empirical treatment of H. pylori infection, but response appears to be geography dependent. Studies have also documented that ITP patients in East Asian countries are more likely to express positive antibody titers against H. pylori-specific cytotoxic-associated gene A (CagA), a virulence factor that is associated with an increased risk for gastric diseases including carcinoma. While a definitive mechanism by which H. pylori may induce thrombocytopenia remains elusive, proposed pathways include molecular mimicry of CagA by host autoantibodies against platelet surface glycoproteins, as well as perturbations in the phagocytic activity of monocytes. Traditional treatments of ITP have been largely empirical, involving the use of immunosuppressive agents and immunoglobulin therapy. However, based on the findings of clinical reports emerging over the past 20 years, health organizations around the world increasingly suggest the detection and eradication of H. pylori as a treatment for ITP. Elucidating the exact molecular mechanisms of platelet activation in H. pylori-positive ITP patients, while considering biogeographical differences in response rates, could offer insight into how best to use clinical H. pylori eradication to treat ITP, but will require well-designed studies to confirm the suggested causative relationship between bacterial infection and an autoimmune disease state.
特发性血小板减少性紫癜（ITP）通常是一种排除性诊断，由临床医生在排除其他可识别病因后做出。自1998年加斯巴里尼等人发表报告以来，越来越多的证据表明ITP与慢性幽门螺杆菌（H. pylori）感染之间存在病理生理联系。临床报告描述，在对H. pylori感染进行经验性治疗后，约50%的慢性ITP患者的ITP症状会自发缓解，但反应似乎因地域而异。研究还记录了东亚国家的ITP患者更有可能表达针对H. pylori特异性细胞毒素相关基因A（CagA）的阳性抗体滴度，CagA是一种毒力因子，与包括癌症在内的胃部疾病风险增加有关。虽然幽门螺杆菌可能导致血小板减少的确切机制仍不清楚，但提出的途径包括宿主针对血小板表面糖蛋白的自身抗体对CagA的分子模拟，以及单核细胞吞噬活性的扰动。ITP的传统治疗在很大程度上是经验性的，包括使用免疫抑制剂和免疫球蛋白疗法。然而，根据过去20年出现的临床报告结果，世界各地的卫生组织越来越多地建议检测和根除幽门螺杆菌作为ITP的一种治疗方法。在考虑反应率的生物地理差异的同时，阐明幽门螺杆菌阳性ITP患者血小板激活的确切分子机制，可能有助于深入了解如何最好地利用临床幽门螺杆菌根除来治疗ITP，但这需要精心设计的研究来证实细菌感染与自身免疫疾病状态之间建议的因果关系。
