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Summary Chronic Immune Thrombocytopenia (cITP) is an acquired immune‐mediated disease associated with a T‐helper cell type 1 (Th1) immune polarization, whose genetic risk factors, however, are largely unknown. We investigated polymorphisms in promoter regions of genes that code molecules involved in proinflammatory immune response [IL1B−31T/C, IL1RN variable number tandem repeats (VNTR), IL2−330T/G, and TNF−307G/A] as well as in genes that code Toll like receptors (TLR) (TLR2 Arg753Gln, TLR4 Asp299Gly and TLR5 Arg392stop) in 122 patients with cITP and 541 blood donors. The frequencies of the IL1RN polymorphic allele 2 (P = 0·001) and of the IL2−330 polymorphic allele G (P = 0·004) were significantly higher in cITP patients than in blood donors. In logistic analysis adjusting for age and gender, the polymorphisms remained independently associated with cITP. Enhanced serum concentrations of interleukin (IL)‐1α and IL‐1β were observed in cITP (P < 10−3) and blood donor (P = 0·04) carriers of the IL1RN*2. Also, the serum levels of IL‐2 and γ‐interferon (IFN‐γ) were increased in cITP patients (P < 10−3 and P = 0·04 respectively) and blood donors (P < 10−3 and P = 0·03 respectively) harbouring the IL2−330G allele. Here we demonstrated that IL2−330G and IL1RN*2 are independently associated with cITP and are functional in vivo, which strongly suggests that they contribute to the pathogenesis of cITP.

SummaryHelicobacter pylori eradication induces platelet recovery in a subgroup of patients with chronic immune thrombocytopenia (cITP), but the mechanisms involved are still not understood. We aimed to evaluate the effect of H. pylori eradication on platelet response and to identify the associated serum cytokine profile in 95 patients with cITP. Serum cytokine concentrations were determined by enzyme-linked immunosorbent assay prior to and 6 months after H. pylori eradication. Remission of cITP was observed in 17 (28Á8%) of 59 patients in whom the bacterium was eradicated. Six months after treatment, a significant reduction in the concentrations of T-helper (Th) 1 and Th17 cells and an increase in T regulatory (Treg) and Th2-cell commitment cytokines were observed in patients who recovered, but not in those whose platelet count did not recover. Patients who had a platelet response to eradication of the bacteria had higher pre-treatment serum levels of c-interferon (IFNG, IFN-c), transforming growth factor-b (TGFB1, TGF-b) and interleukin 17 (IL17A, IL-17) than patients who did not respond, but only higher pre-treatment TGFB1 levels was independently associated with platelet response. In conclusion, amelioration of cITP after eradication of H. pylori was linked to a more efficient suppression of Th1 and Th17 response and a more pronounced Treg cell response.

Helicobacter pylori infection Chronic gastritis cagA-positive strains Pathogenesis