Eradication of Helicobacter pylori Shifts the Balance of Fcγ Receptors on Monocytes toward the Inhibitory FcγRIIB in Patients with Chronic ITP.

Recent studies from Italy and Japan demonstrated that more than a half of patients with idiopathic thrombocytopenic purpura (ITP) infected with Helicobacter pylori (H. pylori) achieved a partial or complete platelet recovery after eradication of H. pylori, suggesting a causal link between H. pylori and ITP. To examine the role of H. pylori infection in the pathogenic process of ITP, autoimmune response to platelet GPIIb/IIIa as well as phenotypic and functional properties of circulating monocytes were serially evaluated in ITP patients who were treated with a standard eradication regimen (a combination of lansoprazole, amoxicillin and clarithromycin for one week) irrespective of the presence or absence of H. pylori infection. Thirty-five adult patients with chronic ITP and a platelet count below 100 × 10⁹/L were enrolled. Platelet counts, proportion of reticulated platelets, plasma thrombopoietin, expression levels of FcγRI, FcγRII, CD86 and HLA-DR on circulating monocytes assessed by flow cytometry, capacity of circulating monocytes to uptake FITC-dextran, circulating anti-GPIIb/IIIa antibody-producing B cells, and T-cell proliferative responses to GPIIb/IIIa and tetanus toxoid were evaluated at 0, 1, 12, and 24 weeks after initiation of the eradication therapy. H. pylori infection was found in 24 (69%) patients by means of a urea breath test. At baseline, circulating monocytes from H. pylori-positive patients exhibited up-regulated expression of FcγRI and HLA-DR, down-regulated expression of FcγRII, and enhanced phagocytic capacity, compared with those from H. pylori-negative patients (all for p < 0.05). All H. pylori-positive patients were successfully eradicated, and a significant platelet response was observed in 13 (54%) eradicated patients, but in none of 11 H. pylori-negative patients. Anti-GPIIb/IIIa antibody-producing B cells and proportion of reticulated platelets were significantly reduced at 12 and 24 weeks in 13 H. pylori-positive responders as well as, to a lesser extent, in 11 H. pylori-positive non-responders (p < 0.05), but not in 11 H. pylori-negative patients. In H. pylori-positive responders, up-regulated FcγRI expression and enhanced phagocytic capacity of monocytes were decreased at 12 and 24 weeks (p < 0.05), but HLA-DR expression remained high. On the other hand, down-regulated FcγRII expression on monocytes was significantly increased at week 24 (p = 0.02). These changes were not observed in H. pylori-negative patients, although similar trends were found in H. pylori-positive non-responders without statistical significance. When gene expression of a stimulatory receptor FcγRIIA and an inhibitory receptor FcγRIIB was independently assessed on the sorted monocytes by quantitative real-time PCR, the FcγRIIA/IIB expression ratio was significantly reduced in H. pylori-positive responders at one week, but not in H. pylori-negative patients. In summary, H. pylori infection plays a role in the ITP pathogenesis by altering FcγR balance of monocytes/macrophages in favor of activating receptors. A platelet recovery observed in a subset of ITP patients after the H. pylori eradication is likely to be mediated by a change in the FcγR balance toward the inhibitory FcγRIIb.