Therapeutic Action of Helicobacter pylori (H. pylori) Eradication in Patients with Chronic ITP - Lessons from Eradication Therapy on H. pylori-Negative Patients.
Authors: Asahi Atsuko , Kuwana Masataka , Suzuki Hidekazu , Okazaki Yuka , Masaoka Tatehiro , Ikeda Yasuo 
Published: October 2019

Abstract
Helicobacter pylori (H. pylori), a gram-negative bacterium, is suspected to be involved in the pathogenesis of idiopathic thrombocytopenic purpura (ITP). Recent studies from Italy and Japan showed that more than a half of H. pylori-positive patients with ITP achieved a partial or complete platelet recovery after eradication of H. pylori. To examine therapeutic action of H. pylori eradication therapy, we performed a prospective study in which ITP patients 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-seven adult patients (mean 56.4 years of age) with chronic ITP and a platelet count below 50 x 109/L were enrolled. Platelet counts and circulating anti-GPIIb/IIIa antibody-producing B cell frequencies were monitored at 0, 1, 12, and 24 weeks after initiation of the eradication therapy. H. pylori infection was found in 26 (70%) patients by means of a urea breath test, while the remaining 11 patients were negative for all of a urea breath test, a stool antigen test, and a serum antibody test. Although H. pylori-positive patients tended to be older than H. pylori-negative patients (P = 0.06), other characteristics, such as disease duration, previous treatment regimens, platelet count and anti-GPIIb/IIIa antibody-producing B cells, were not different between these 2 groups. Twenty-five (96%) H. pylori-positive patients were successfully eradicated. At 24 weeks, a significant response (platelet count > 100 x 109/L) was observed in 16 (64%) of 25 eradicated patients, but not in a H. pylori-positive patient who failed in the eradication. In addition, a platelet count did not change at all in 11 H. pylori-negative patients, indicating that platelet recovery results from eradication of H. pylori itself, but not from immunomodulatory effects of the drugs used or eradication of microorganisms other than H. pylori. Anti-GPIIb/IIIa antibody-producing B cells were significantly reduced at 12 and 24 weeks in H. pylori-positive responders (P < 0.0001) as well as, to a lesser extent, in H. pylori-positive non-responders (P = 0.02), but not in H. pylori-negative patients (P = 1.0). In the majority of responders, a platelet count was already increased at one week when anti-GPIIb/IIIa antibody-producing B cells were not decreased. To further evaluate therapeutic action of H. pylori eradication, changes of anti-GPIIb/IIIa antibody-producing B cell frequency at one week after initiation of varuous therapies were additionally examined in ITP patients who responded to intravenous immunoglobulin (n = 6), corticosteroids (n = 7), or splenectomy (n = 7). The B cell frequency was significantly decreased after treatment with corticosteroids and splenectomy (both for P < 0.0001), whereas a stable B cell frequency observed at one week after H. pylori eradication was compatible with intravenous immunoglobulin that primarily inhibits Fc receptor-mediated platelet phagocytosis. In summary, this prospective study confirms effectiveness of H. pylori eradication for chronic ITP and a direct role of H. pylori infection in the pathogenesis of ITP. The platelet recovery after H. pylori eradication is likely to be mediated through complex processes; inhibition of Fc receptor-mediated phagocytosis followed by suppression of anti-platelet autoantibody production.