Helicobacter pylori eradication shifts monocyte Fcγ receptor balance toward inhibitory FcγRIIB in immune thrombocytopenic purpura patients
Atsuko Asahi, … , Yasuo Ikeda, Masataka Kuwana
Atsuko Asahi, … , Yasuo Ikeda, Masataka Kuwana
Published July 24, 2008
Citation Information: J Clin Invest. 2008;118(8):2939-2949. https://doi.org/10.1172/JCI34496.
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Research Article

Helicobacter pylori eradication shifts monocyte Fcγ receptor balance toward inhibitory FcγRIIB in immune thrombocytopenic purpura patients

Abstract

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. pylori–positive 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.

Authors

Atsuko Asahi, Tetsuya Nishimoto, Yuka Okazaki, Hidekazu Suzuki, Tatsuhiro Masaoka, Yutaka Kawakami, Yasuo Ikeda, Masataka Kuwana

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Figure 4

Change in FcγRIIB expression levels in circulating monocytes from ITP patients before and after initiation of the H. pylori eradication.

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Change in FcγRIIB expression levels in circulating monocytes from ITP pa...
(A) FcγRIIA/IIB mRNA expression ratio on monocytes prior to treatment was determined by quantitative TaqMan PCR in 11 ITP patients infected with H. pylori and 5 uninfected ITP patients. The difference between the 2 groups was analyzed using the Mann-Whitney U test. (B) The FcγRIIA/IIB expression ratio on monocytes was serially measured prior to treatment and at 1 and 12 wk after initiation of the H. pylori eradication regimen in 6 H. pylori–positive ITP responders, 5 H. pylori–positive ITP nonresponders, and 5 H. pylori–negative ITP nonresponders. Results are shown as the mean + SD. Changes in the values at 1 and 12 wk from the baseline value taken at wk 0 were assessed by paired t test. **P < 0.01 compared with pre-treatment. Representative RT-PCR results for the expression of FcγRIIA, FcγRIIB, and GAPDH are shown for each patient group. (C) The protein expression of FcγRIIB on monocytes prior to treatment and 12 wk after initiation of the H. pylori eradication regimen in a representative H. pylori–positive responder and nonresponder. Open histograms show the cells stained with isotype-matched control Ab, and closed histograms show anti-FcγRIIB mAb–treated cells. (D) Expression levels of FcγRIIB on monocytes were measured prior to treatment and 12 wk after initiation of the H. pylori eradication regimen in 5 H. pylori–positive ITP responders, 4 H. pylori–positive ITP nonresponders, and 3 H. pylori–negative ITP nonresponders.