Eradication of Helicobacter pylori Shifts the Balance of Fcγ Receptors on Monocytes toward the Inhibitory FcγRIIB in Patients with Chronic ITP.
Authors: Kuwana Masataka , Asahi Atsuko , Suzuki Hidekazu , Okazaki Yuka , Ikeda Yasuo 
Published: April 2020

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 &lt; 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 &lt; 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 &lt; 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.