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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces cell apoptosis by transducing apoptosis signals. Recently, accumulating evidence demonstrated that TRAIL regulates autoimmune inflammation and immune cell homeostasis in several autoimmune animal models, suggesting a novel immunoregulatory role of TRAIL in autoimmune diseases. However, the impact of TRAIL in inflammatory bowel disease is yet undefined. This study is to address the therapeutic effects and immunoregulatory role of TRAIL in autoimmune gut inflammation. We demonstrated herein that TRAIL significantly suppressed gut inflammation and reduced the severity of colitis in a dextran sodium sulfate (DSS)-induced colitis model. Suppression of gut inflammation was not due to induction of apoptosis in colonic T cells, dendritic cells, or epithelium cells by TRAIL. In contrast, TRAIL directly inhibited activation of colitogenic T cells and development of gut inflammation in an adoptive transfer-induced colitis model. The anti-inflammatory effects of TRAIL on colitis were abolished when T cells from TRAIL receptor (TRAIL-R) knockout mice were adoptively transferred, suggesting that TRAIL regulates autoreactive colitogenic T-cell activation in the development of gut inflammation. Our results demonstrate that TRAIL effectively inhibited colonic T-cell activation and suppressed autoimmune colitis, suggesting a potential therapeutic application of TRAIL in human inflammatory bowel disease.

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes not only joint pain but also bone destruction resulting in impairment of quality of life. Tumor necrosis factor inhibitors have improved prognosis of patients with rheumatoid arthritis dramatically, especially in combination with methotrexate, however, the optimal dose of the concomitant methotrexate is unclear.ObjectivesTo evaluate the efficacy and safety of adalimumab in combination with reduced dose of methotrexate in patients with early RA with inadequate response to methotrexate.MethodsThe MIRACLE study was a multinational, randomized, open-label study in patients with RA with inadequate response to methotrexate conducted in Asia. It compared low dose and high dose methotrexate upon starting adalimumab. Methotrexate-naive patients with RA with a disease duration of less than two years started methotrexate at 6 to 8 mg/week and increased it to the maximum tolerable dose by week 12. Patients who have not achieved remission according to simplified disease activity index (SDAI) despite methotrexate ≥ 10 mg/week at week 24 were randomised to the maximum tolerable dose of methotrexate group (10 to 25 mg/week) or the reduced dose group (6 to 8 mg/week) and started to receive subcutaneous adalimumab 40 mg every other week. The primary endpoint was non-inferiority in the achievement of SDAI remission at week 48 in the reduced dose group compared with the maximum tolerable dose group with a non-inferiority margin of -15% based on two-sided 90% confidence interval. (NCT03505008)ResultsA total of 300 patients were enrolled in the study. Among them, 291 started methotrexate and were included in the analysis. The mean age was 57.7±15.2 years, female was 74.6%, and the mean disease duration from the diagnosis of RA was 21.1±56.2 days. Anti-CCP antibody was positive in 211 (73.0%) and the mean SDAI at study enrollment was 26.5±12.4. At week 24, with the mean dose of methotrexate of 12.6±2.9 mg/week, 108 patients (37.1%) achieved remission according to SDAI and continued MTX monotherapy. 134 patients (46.0%) were randomised and started adalimumab with 68 patients in the maximum tolerable dose group and 66 patients in the reduced dose group. At week 48, the remission achievement rates were 38.4 % and 44.8 %, respectively, with the adjusted risk difference of the reduced dose group to the maximum tolerable dose group of 6.4% (-7.0% to 19.8%, 90% CI), which met the criterion for noninferiority. No significant difference was found in health assessment questionnaire disability index ≤0.5 (59.1% vs 62.0%, respectively, p=0.72) and in radiological remission rates (Δmodified total Sharp score ≤0.5, 66.3% vs 62.0 %, respectively, p=0.59). Adverse drug reactions tended to be more frequent in the maximum tolerable dose group than in the reduced dose group (22.1% vs 9.1%, respectively, p=0.06).ConclusionThe MIRACLE randomised study demonstrated that, in patients with inadequate response to methotrexate, the efficacy of adalimumab with reduced dose of concomitant methotrexate was not inferior to that with maximum tolerable dose of methotrexate with better safety profile.Disclosure of InterestsHiroya Tamai Speakers bureau: Eisai, Grant/research support from: Eisai, Kei Ikeda Speakers bureau: AbbVie, Eisai, Eli Lilly, Novartis, Gilead, Asahi-Kasei, Grant/research support from: Mitsubishi-Tanabe, Toshiaki Miyamoto: None declared, Hiroaki Taguchi: None declared, Chang-Fu Kuo: None declared, Kichul Shin: None declared, Shintaro Hirata Speakers bureau: AbbVie, Asahi-Kasei, Astellas, Ayumi, Bristol Myers Squibb, Celgene, Chugai, Eisai, Eli Lilly, Gilead, Glaxo SmithKline, Janssen, Kyorin, Novartis, Pfizer, Sanofi, Tanabe-Mitsubishi, UCB, Paid instructor for: AbbVie, Mitsubishi-Tanabe, Consultant of: AbbVie, Astellas, Bristol Myers Squibb, Eisai, Gilead, Ily Lilly, Grant/research support from: AbbVie, Asahi-Kasei, Eisai, Otsuka, Sanofi, Shionogi, Chugai, Pfizer, Tanabe-Mitsubishi, Eli Lilly, UCB, yutaka okano: None declared, Shinji Sato Speakers bureau: AbbVie, Eisai, Grant/research support from: AbbVie, Eisai, Hidekata Yasuoka Speakers bureau: AbbVie, Asahi Kasei Pharma, Astellas, Daiichi-Sankyo, Eisai, Kissei, Takeda, Mitsubishi-Tanabe, Chugai, Novartis, Eli Lilly, Pfizer, Janssen, Sanofi, Teijin, Boehringer-Ingelheim, Bayer, Glaxo Smith Kline, Paid instructor for: AbbVie, Consultant of: AbbVie, Asahi Kasei, Grant/research support from: Mitsubishi-Tanabe, Takeda, Daiichi-Sankyo, Chugai, Bristol-Myers, MSD, Astellas, In Ah Choi Speakers bureau: Abbvie, Eisai, Sung-Hwan Park: None declared, Meng-Yu Weng Paid instructor for: Novartis, Eli Lilly, ChuGai, Abbvie, Consultant of: Abbvie, Masataka Kuwana Speakers bureau: Astellas, Asahi Kasei Pharma, Boehringer-Ingelheim, Chugai, Eisai, Janssen, Mochida, Nippon Shinyaku, Ono Pharmaceuticals, Pfizer, Mitsubishi-Tanabe, Consultant of: Boehringer-Ingelheim, Kissei, Mochida, Grant/research support from: AbbVie, Asahi Kasei Pharma, Boehringer-Ingelheim, Chugai, Eisai, MBL, Nippon Shinyaku, Ono Pharmaceuticals, Mitsubishi-Tanabe, Yun Jong Lee Grant/research support from: Yuhan, Tomonori Ishii Speakers bureau: Chugai, Mitsubishi-Tanabe, Glaxo Smith Kline, Pfizer, Eli Lilly, Janssen, AbbVie, Eisai, Astellas, Jinhyun Kim: None declared, Hideto Kameda Speakers bureau: AbbVie, Pfizer, Consultant of: AbbVie, Grant/research support from: AbbVie, Eisai, Toshihisa Kojima Speakers bureau: AbbVie, Pfizer, Eisai, Grant/research support from: AbbVie, Han Joo Baek: None declared, Ping-Ning Hsu: None declared, Chun-Ming Huang Paid instructor for: Abbvie, Pfizer, Tien-Tsai Cheng Paid instructor for: Abbvie, Grant/research support from: Abbvie, Wan-Yu Sung: None declared, Takehiro Taninaga Shareholder of: Eisai.co.,Ltd., Employee of: Eisai.co.,Ltd., Masahiko Mori Shareholder of: Eisai.co.,Ltd., Employee of: Eisai.co.,Ltd., Hideaki Miyagishi Shareholder of: Eisai.co.,Ltd., Employee of: Eisai.co.,Ltd., Yasunori Sato Speakers bureau: Eisai Co., Ltd. Kowa Company, Ltd., Consultant of: MOCHIDA PHARMACEUTICAL CO., LTD, Tsutomu Takeuchi Speakers bureau: Astellas, AbbVie, Ayumi, Bristol Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Glaxo Smith Kline, Janssen, Mitsubishi-Tanabe, Nippon-kayaku, Novartis, Pfizer, Sanofi, UCB, Grant/research support from: Asahi Kasei, AbbVie, Ayumi, Boehringer-Ingelheim, Chugai, Eisai, Eli Lilly, Mitsubishi-Tanabe, Sanofi, UCB, Yuko Kaneko Speakers bureau: Asahi Kasei, Astellas, Ayumi, Bristol Myers Squibb, Chugai, Eisai, Elli Lilly, Mitsubishi-Tanabe, Novartis, UCB, Grant/research support from: AbbVie, Chugai, Eisai, Mitsubishi-Tanabe, UCB.

Background:Methotrexate (MTX) is the first-line therapy for rheumatoid arthritis (RA). The concentrations of MTX-polyglutamates (PG) in erythrocytes, an active form of MTX, are useful markers for the optimal usage of MTX in patients with RA. The concentrations of MTX-PG have been reported to be different between Japanese and Caucasians. However, the difference among Asian ethnicity remains unclear.Objectives:To examine MTX-PG concentrations in association with MTX dose during the first 24 weeks after the initiation of MTX for newly diagnosed RA patients in Japan, Korea and Taiwan.Methods:MIRACLE study is a multicenter, open-label, randomized, 48 weeks interventional study conducted in Japan, Korea and Taiwan to evaluate non-inferiority of low dose to high dose of MTX as an add-on therapy to adalimumab in 300 patients with RA who do not achieve remission after 24 weeks MTX monotherapy in stipulated dosage. In the first 24 weeks, MTX was started at 6 to 8 mg/week for newly diagnosed RA patients, and promptly escalated to the maximum tolerable dose in 12 weeks in principle. This interim data evaluation was intended to investigate the differences among countries in the relationship between MTX dose, safety and MTX-PG concentrations in erythrocytes during the first 24 weeks. The efficacy of the treatment is not included at this point.Results:A total of 166 patients (106 in Japan, 35 in Korea, 25 in Taiwan) were included in this interim data. The age at treatment initiation was 57.2 years old on average and female was 79.5%. The time course changes in total and individual MTX-PG levels differed in the three countries. At 24 weeks, whereas the mean total MTX-PG concentrations were comparable (112.9 nmol/L in Japan, 104.4 nmol/L in Korea, and 115.7 nmol/L in Taiwan) with a dose of MTX of 12.3 mg/week, 14.1 mg/week, and 12.2 mg/week, respectively, the individual MTX-PG concentrations were different. The MTX-PG1 and MTX-PG2 concentrations were lower in Korea than Japan and Taiwan whereas MTX-PG3, MTX-PG4 and MTX-PG5 concentrations were the highest in Korea.Conclusion:The distribution of short-chain and long-chain MTX-PG concentrations were various among Asian countries despite similar dose of MTX administration: NCT03505008.Disclosure of Interests:Hiroya Tamai: None declared, Yuko Kaneko Speakers bureau: AbbVie, Astellas, Ayumi, Bristol–Myers Squibb, Chugai, Eisai, Eli Lilly, Hisamitsu, Jansen, Kissei, Kirin, Pfizer, Sanofi, Takeda, Tanabe-Mitsubishi, and UCB., Grant/research support from: Sanofi, Hideto Kameda Speakers bureau: AbbVie, Pfizer, Consultant of: AbbVie, Grant/research support from: AbbVie, Eisai, Masataka Kuwana Speakers bureau: Astellas, Asahi Kasei Pharma, Boehringer- Ingelheim, Chugai, Eisai, Janssen, Mochida, Nippon Shinyaku, Ono Pharmaceuticals, Pfizer, Mitsubishi-Tanabe, Consultant of: Corbus, Grant/research support from: AbbVie, Asahi Kasei Pharma, Boehringer- Ingelheim, Chugai, Eisai, MBL, Nippon Shinyaku, Ono Pharmaceuticals, Mitsubishi-Tanabe, Yutaka Okano: None declared, Tomonori Ishii Speakers bureau: Chugai, Mitsubishi- Tanabe, Glaxo Smith Kline, Pfizer, Eli Lilly, Janssen, AbbVie, Eisai, Astellas, Kei Ikeda Speakers bureau: AbbVie, Eli Lilly, Novartis, Mitsubishi-Tanabe, Eisai, BMS, Grant/research support from: Mitsubishi-Tanabe, Hiroaki Taguchi: None declared, Shinji Sato: None declared, Toshiaki Miyamoto: None declared, Shintaro Hirata Speakers bureau: AbbVie, Asahi Kasei Pharma, Astellas, Ayumi, Bristol Myers Squibb, Chugai, Eisai, Eli Lilly, Janssen, Glaxo Smith Kline, Kissei, Pfizer, Sanofi, Mitsubishi- Tanabe, UCB, Paid instructor for: AbbVie, Mitsubishi- Tanabe, Consultant of: AbbVie, Eisai, Gilead, Grant/research support from: AbbVie, Chugai, Mitsubishi-Tanabe, UCB, Hidekata Yasuoka Speakers bureau: AbbVie, Asahi Kasei Pharma, Astellas, Daiichi- Sankyo, Eisai, Kissei, Takeda, Mitsubishi- Tanabe, Chugai, Novartis, Eli Lilly, Pfizer, Janssen, Sanofi, Teijin, Boehringer- Ingelheim, Bayer, Glaxo Smith Kline, Paid instructor for: AbbVie, Consultant of: AbbVie, Asahi Kasei, Grant/research support from: Mitsubishi-Tanabe, Takeda, Daiichi-Sankyo, Chugai, Bristol-Myers, MSD, Astellas, Toshihisa Kojima Speakers bureau: AbbVie, Pfizer, Eisai, Grant/research support from: AbbVie, Sung-Hwan Park: None declared, Kichul Shin: None declared, Han Joo Baek: None declared, Yun Jong Lee Grant/research support from: research fund, In Ah Choi Speakers bureau: Abbvie, Eizai, Grant/research support from: Abbvie, Eizai, Jinhyun Kim: None declared, Ping-Ning Hsu: None declared, Chang-Fu Kuo: None declared, Chun-Ming Huang Paid instructor for: AbbVie, Pfizer, Meng-Yu Weng Consultant of: AbbVie, Wan-Yu Sung: None declared, Wen-Chan Tsai: None declared, Tien-Tsai Cheng Paid instructor for: AbbVie, Grant/research support from: AbbVie, Takehiro Taninaga Shareholder of: Eisai Co., Ltd., Employee of: Eisai Co., Ltd., Masahiko Mori Shareholder of: Eisai Co., Ltd., Employee of: Eisai Co., Ltd., Hideaki Miyagishi Employee of: Eisai Co., Ltd., Yasunori Sato: None declared, Tsutomu Takeuchi Speakers bureau: Astellas, Abbvie, Daiichi Sankyo, Ayumi, Eisai, GlaxoSmithKline, Mitsubishi Tanabe, Chugai, Novartis, Eli Lilly, Pfizer, Bristol Myers Squibb, Janssen, UCB, TaishoToyama, Sanofi–Aventis, Nipponkayaku, Taiho, Gilead, Boehringer Ingelheim, Grant/research support from: Asahikasei, Astellas, Abbvie, Daiichi Sankyo, Ayumi, Eisai, Takeda, Mitsubishi Tanabe, Chugai, Eli Lilly, UCB, Sanofi–Aventis, Nipponkayaku, Boehringer Ingelheim

The host genetic factors that determine the clinical outcomes of Helicobacter pylori-infected individuals remain unclear.To elucidate the risks of host interleukin-1 (IL-1) genetic polymorphisms and H. pylori infection in the development of gastric cancer.In a case-control study of 164 controls and 142 patients with gastric cancer, the IL-1B-511 biallelic polymorphisms and the IL-1RN penta-allelic variable number of tandem repeats were genotyped.The carriage of IL-1RN*2, male gender, old age and H. pylori infection independently increased the risk of gastric cancer, with odds ratios of 3.3 [95% confidence interval (CI), 1.4-7.7], 2.1 (95% CI, 1.2-3.8), 5.3 (95% CI, 3.1-9.0) and 2.2 (95% CI, 1.3-3.8), respectively. H. pylori-infected individuals who were carriers of IL-1RN*2 showed increased risks of both intestinal and diffuse types of gastric cancer, with odds ratios of 11.0 and 8.7, respectively. In addition, these individuals also had a higher score of intestinal metaplasia in the corpus than did uninfected non-carriers.This study is the first to verify IL-1RN*2 as an independent factor governing the development of gastric cancer in Asian individuals. A combination of H. pylori testing and host genotyping may target the eradication of H. pylori to high-risk individuals.

Although the eradication of Helicobacter pylori infection benefits patients with gastric or duodenal ulcers, the value of eradicating the infection in the patients with functional dyspepsia (FD) remains controversial.To determine whether eradicating H. pylori can prevent the subsequent development of ulcers or relieve the symptoms of functional dyspepsia patients.In a double-blind, placebo-controlled trial, 161 patients infected with H. pylori who had functional dyspepsia were randomly assigned to 7 days of treatment with a lansoprazole-based triple therapy or placebo and then followed for 1 year. The main outcome measures were the development of peptic ulcers and the resolution of symptoms.H. pylori was eradicated in 63 out of 81 patients (78%) in the treatment group and none of the 80 patients (0%) in the placebo group. During the follow-up period, two patients in the treatment group and six patients in the placebo group developed peptic ulcers at repeat endoscopy (2.5% vs. 7.5%; 95% CI: -12 to 2). The reduction in ulcer rates was statistically significant in the 'ulcer-like' sub-group (0% vs. 16.7%; 95% CI: -32 to -2), but not in the 'dysmotility-like' and 'unclassifiable' sub-groups. Regarding symptom response, the resolution rates of symptoms were similar between the treatment and placebo groups (58.0% vs. 55.0%, 95% CI: -12 to 18). Additionally, no significant differences existed in the symptom responses between the treatment and control arms in each of the dyspepsia sub-groups.Eradicating H. pylori can prevent the subsequent development of peptic ulcers in the patients with 'ulcer-like' functional dyspepsia. However, this approach does not significantly reduce the symptoms of functional dyspepsia patients.

Chronic Helicobacter pylori infection leads to the development of mucosa-associated lymphoid tissue (MALT), gland atrophy, intestinal metaplasia, and in certain individuals, gastric lymphoma and adenocarcinoma. We conducted a prospective study to determine the effect of H pylori eradication on the development of MALT, gland atrophy and intestinal metaplasia.From July 1995 to October 1996, 63 consecutive patients with H pylori-associated peptic ulcer disease were enrolled in a bacterial eradication trial. The grade of MALT and the degree of gastritis of the antrum were assessed using Wotherspoon's scale and the Sydney system before treatment, and at eight weeks and one year after H pylori eradication therapy.During the study period, 43 patients received complete follow-up. In the patient group with eradication failure (n = 22), MALT score was significantly decreased at the end of the eighth week (p0.05) but returned to the initial level by one year of follow-up. There were no changes in the scores for inflammation, neutrophil activity, gland atrophy or intestinal metaplasia at the end of the eighth week and at one year following H pylori eradication therapy. In contrast, there was a marked reduction in the MALT, inflammation, and activity scores at eight weeks (p0.01,0.05 and0.05, respectively) and one year after treatment (p0.05,0.001 and0.001, respectively) in the patient group with successful eradication (n = 21). However, no significant changes in gland atrophy and intestinal metaplasia were observed during the follow-up period.Eradication of H pylori leads to regression of MALT in the stomach, but the degrees of gland atrophy and intestinal metaplasia remain unchanged, even after one-year of follow-up.

This study investigates the cell proliferation and the expression of p53 protein in Helicobacter pylori (H. pylori)-associated gastritis and assesses the effect of bacterial eradication on these epithelial factors.Seventy-nine patients with H. pylori-associated gastritis were randomized into the control group (n = 38) and anti-H. pylori group (n = 41). Each patient received endoscopic examinations with gastric biopsy before and 8 weeks after the treatment. The specimens from gastric antrum were immunostained for monoclonal antibodies against the proliferating cell nuclear antigen (PCNA) and p53 protein.In the control group, the total labeling index (L.I.) of PCNA and the positive index (P.I.) of p53 in the whole foveolar epithelium were unchanged after treatment. In the anti-H. pylori group, 35 of 41 cases (85.3%) achieved eradication of H. pylori. Amongst the H. pylori-eradicated cases, the total L.I. of PCNA in the whole foveolar epithelium did not meaningfully alter after H. pylori elimination (p0.05). However, a significant reduction of L.I. was observed in the middle compartments of the gastric pits (before vs. after treatment: 14.0 vs. 7.3, p0.05). With regard to the p53 expression, the P.I.s were significantly decreased in the whole foveolar epithelium (before vs. after treatment: 0.57 vs. 0.17, p0.05) and in each compartment of the gastric pits (before vs. after treatment: [upper compartment]: 0.34 vs. 0.15, p0.05; [middle compartment]: 0.67 vs. 0.23, p0.05; [lower compartment]: 0.71 vs. 0.20, p0.05) after eradication of H. pylori.Bacterial eradication reverses the hyperproliferating status of the foveolar epithelium in patients with H. pylori gastritis and leads to a decrease in p53 accumulation in the epithelial cells.

House dust mite (HDM) Dermatophagoides pteronyssinus is the most important source of indoor allergens that cause allergic diseases in Taiwan. We prepared purified HDM allergens (Der p 1, Der p 2 and Der p 5) to detect allergen-specific immunoglobulin (Ig) E responsiveness among a large number of test subjects. The robust genetic typing system for HLA class II genes also facilitated the study on association of HLA and allergic response toward HDM.This study intended to investigate the association between HLA class II alleles and the IgE responsiveness to the major allergens from HDM, D. pteronyssinus.Two hundred and forty-eight subjects were selected for HLA association study. Plasma HDM allergen (Der p 1, Der p 2, Der p 5) -specific IgE and Der p 2-specific IgG antibodies were detected by ELISA, while HLA class II -DRB1, -DQA1, -DQB1, -DPB1 genetic polymorphism was determined by polymerase chain reaction/sequence-specific oligonucleotide probe hybridization (PCR/SSOPH). Statistical comparison of the allelic distribution of each HLA class II genes among the individuals with/without HDM allergen-specific IgE and IgG antibodies were performed.There was no significant association between HLA DRB1, DQB1, DQA1 alleles and HDM-specific IgE responsiveness noted. Only DRB1*0803 and the linked DQA1*0103 alleles showed positive association with Der p 5-specific IgE responsiveness. However, we found that HLA-DPB1*1301 predisposed subjects to IgE responsiveness to HDM Der p 5. HLA DPB1*0501 was weakly associated with the IgE responsiveness to HDM Der p 1 and Der p 5. There was a strong negative association between the HLA-DPB1*0201 allele with IgE responsiveness to Der p 1 (OR: 0.30, P/= 0.0001, P/= 0.0007, Pc/= 0.010).We clearly observed the association between HLA DPB1 alleles and specific IgE responsiveness to HDM major allergens. The molecular mechanism of HLA-DPB1*0201 involvement in protecting subjects from HDM-specific IgE responsiveness awaits further investigation.

Background Our earlier study showed that certain proportion of early-stage H. pylori (HP)-positive gastric diffuse large B-cell lymphoma (DLBCL) with features of mucosa-associated lymphoid tissue (MALT), DLBCL(MALT), could achieve long-term complete pathological remission (pCR) after frontline HP eradication therapy (HPE). In this retrospective, explorative study, we evaluate the efficacy of HPE on early-stage gastric DLBCL without features of MALT, the pure (de novo) DLBCL, in comparison with its efficacy on high-grade transformed gastric MALT lymphoma, the DLBCL(MALT). Methods A total of 50 patients of stage IE/IIE1, HP-positive gastric DLBCL with frontline HPE treatment were included. Of them, 16 patients with pure (de novo) DLBCL were retrospectively identified from medical/pathologic review and 34 patients with DLBCL (MALT) were an expanded cohort of one previously reported multicenter prospective study. pCR was defined as regression of DLBCL to Wotherspoon grade 2 or less in all histologic sections of follow-up endoscopic biopsies. Results HP infection was successfully eradicated in 100% (16/16) of the pure (de novo) DLBCL and 94.1% (32/34) of the DLBCL(MALT) patients. A total of 68.8% (11/16) of pure (de novo) DLBCL and 56.3% (18/32) of DLBCL(MALT) patients achieved pCR after HPE. The median time-to-pCR was 2.1 months (95% CI, 0.6–3.7) for pure (de novo) DLBCL and 5.0 months (95% CI, 2.8–7.5) for DLBCL(MALT) (P = 0.024). At a median follow-up of 7.7 years (95% CI, 4.5–10.9), all patients with pCR after HPE were alive and free of lymphoma, except one patient with pure (de novo) DLBCL died of lung cancer. Conclusions Similar to DLBCL(MALT), a substantial portion of early-stage, HP-positive gastric pure (de novo) DLBCL remains HP-dependent and responds to antibiotic treatment. Prospective studies to validate the findings are warranted.

Background We recently reported that a direct contact of Helicobacter pylori (HP) with B cells resulted in CagA translocation into the cells (Cancer Res 2010;70:5740-8). The translocated CagA further activates extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK), and up-regulates the expressions of Bcl-2 and Bcl-xL. In this study, we sought to verify if CagA exists in the malignant B cells of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Methods Expression of CagA protein, phospho-SHP-2, phospho-ERK, phospho-p38MAPK, Bcl-2 and Bcl-xL in a series of 26 gastric MALT lymphoma was determined by immunohistochemistry. Western blot analysis was done to confirm immunohistochemical detection of CagA and biopsies from non-gastric MALT lymphoma served as negative controls. The association of CagA expression and the tumor response to HP-eradication (HPE) therapy was evaluated in 77 stage IE/IIE1 low-grade gastric MALT lymphoma patients. Results The expression of CagA was detected in 35 (45.5%) of 77 patients. CagA expression was closely associated with the expression phospho-SHP-2 (P = .016), phospho-ERK (P Conclusion CagA protein can be translocated into malignant B cells of MALT lymphoma. The expression of CagA in lymphoma cells appears to be biologically and clinically significant. Disclosure All authors have declared no conflicts of interest.

In order to evaluate the biological features and clinical significance of myeloid antigen expression in acute lymphoblastic leukemia (ALL), immunophenotype analysis was performed on leukemic cells from 160 patients diagnosed as ALL by the French, American and British (FAB) criteria using a comprehensive panel of monoclonal antibodies to lymphoid and myeloid associated antigens. Expression of myeloid antigens was found in 32 cases (20%), including 11 out of 49 adults (22.4%) and 21 out of 111 children (18.9%). CD33 was positive in 18 patients (11.3% of the total cases), CD13 in 15 patients (9.4%), CD 11b in 12 patients (7.5%) and CD14 in 1 patient (0.6%). Nine patients expressed two or more myeloid antigens. There were no significant differences in clinical manifestations and hematological pictures between the ALL patients with myeloid antigen expression (My+ ALL) and those without (My- ALL). No consistent chromosomal abnormality was found in My+ ALL. Eighty percent of the childhood and 44.4% of the adult My+ ALL patients achieved complete remission, compared with 87% and 80%, respectively, for childhood and adult My- ALL, but the differences were not statistically significant. After a median follow-up of 2.1 years, there were also no statistically significant associations between myeloid antigen expression and shorter duration of remission or poorer survival rate for patients with both adult and childhood ALL.