Immune thrombocytopenia purpura (ITP) is a bleeding disorder in which platelet-specific autoantibodies cause a loss of platelets. In a subset of patients with ITP and infected with Helicobacter pylori, the number of platelets recovers after eradication of H. pylori. To examine the role of H. pylori infection in the pathogenesis of ITP, the response of 34 ITP patients to treatment with a standard H. pylori eradication regimen, irrespective of whether they were infected with H. pylori, was evaluated. Eradication of H. pylori was achieved in all H. pyloripositive patients, and a significant increase in platelets was observed in 61% of these patients. By contrast, none of the H. pylori-negative patients showed increased platelets. At baseline, monocytes from the H. pylori-positive patients exhibited an enhanced phagocytic capacity and low levels of the inhibitory Fcγ receptor IIB (FcγRIIB). One week after starting the H. pylori eradication regimen, this activated monocyte phenotype was suppressed and improvements in autoimmune and platelet kinetic parameters followed. Modulation of monocyte FcγR balance was also found in association with H. pylori infection in individuals who did not have ITP and in mice. Our findings strongly suggest that the recovery in platelet numbers observed in ITP patients after H. pylori eradication is mediated through a change in FcγR balance toward the inhibitory FcγRIIB. IntroductionImmune thrombocytopenia purpura (ITP) is an autoimmune disorder caused by increased platelet clearance by anti-platelet autoantibodies (1). In 1998, Gasbarrini et al. reported increase in platelet count in ITP patients infected with Helicobacter pylori after successful eradication of this bacterium (2). Recent accumulating evidence in Italy and Japan indicates that the eradication of H. pylori is effective in increasing the platelet count in nearly half of H. pylori-infected patients with idiopathic ITP (3,4). In addition, a recent report showed that this platelet response lasts for years and cases of relapse are few (5). Based on its efficacy, good safety profile, and low cost, H. pylori eradication therapy for adult ITP is becoming very popular in several countries. Some investigators have suggested that the efficacy of H. pylori eradication in ITP patients may be mediated by H. pylori-independent mechanisms, such as immunomodulatory effects of the drugs used for the regimen (3), but we recently reported its complete lack of efficacy in H. pylori-uninfected ITP patients in a prospective study in which the patients were treated with a standard H. pylori eradication regimen irrespective of their H. pylori infection status (6). This finding clearly indicates that the platelet recovery observed in ITP patients after the eradication regimen results from the disappearance of H. pylori itself.

No abstract

To examine the role of genetic factors in development of immune thrombocytopenic purpura (ITP) in association with Helicobacter pylori infection, gene polymorphisms within the loci for human leukocyte antigen class II, interleukin (IL)-1beta (-511), tumor necrosis factor-beta (+252), immunoglobulin (Ig)G1 heavy chain (+643), and Igkappa light chain (+573) were determined in 164 adults with ITP and 75 healthy controls. Of these gene polymorphisms, the IL-1beta (-511) T allele was less frequently detected in H. pylori-infected than in H. pylori-uninfected (58% vs 81%, P = 0.01, odds ratio = 0.31) ITP patients diagnosed before age 50. These findings suggest that a single nucleotide polymorphism within the IL-1beta (-511) may affect susceptibility to early-onset ITP associated with H. pylori infection.

Key Clinical MessageUterine cervical small cell carcinoma is rare and aggressive with no standardized therapy. A patient bearing the advanced chemo‐refractory carcinoma, treated with a tumor vaccine combined with 1 mg/kg of pembrolizumab, showed a transient increase and subsequent sharp decrease of the liver‐metastasized lesion to less than half its maximum diameter.

Key Clinical MessageA patient with chemo‐refractory multiple‐metastatic upper tract urothelial carcinoma (UTUC) treated by monotherapy with autologous formalin‐fixed tumor vaccine (AFTV) resulted in complete remission of the lung and para‐aortic lymph node metastases (ongoing >3 years after AFTV). The tumor was immunohistologically negative for PD‐L1. AFTV will be an attractive treatment option.