Dysregulated TFR and TFH cells correlate with B-cell differentiation and antibody production in autoimmune hepatitis.

Follicular helper T (TFH) cell provides germinal centre (GC) B cell with critical signals for autoantibody production in the immunopathogenesis and progression of autoimmune hepatitis (AIH). However, the immunoregulatory functions of follicular regulatory T (TFR) cell in AIH are still unclear. The numbers of circulating TFR/TFH cells were measured in AIH patients. Moreover, we established experimental autoimmune hepatitis (EAH) model to examine the function of TFR cells on B-cell differentiation and autoantibody production in vivo and vitro. AIH patients had significantly increased numbers of TFH cells and decreased numbers of TFR cells as well as imbalanced TFR/TFH-type cytokines (IL-10, TGF-ß1 and IL-21) compared with healthy controls (HCs). In addition, TFR cell numbers negatively correlated with TFH cell numbers. Also, serum hypergammaglobulinaemia (IgG and IgM) concentration negatively correlated the levels of serum IL-21, but positively correlated with the levels of serum IL-10 in AIH patients. Furthermore, in comparison with control group, significantly higher frequencies of spleen TFR cells but lower frequencies of spleen TFH cells were detected in the EAH group. Further analysis found that TFR cells simultaneously express the phenotypic characteristics of Treg and TFH cells, but exercise as negative regulators of autoantibody production in vitro culture. Our findings demonstrated that dysregulated between TFR and TFH cells might cause excessive production of autoantibodies and destruction of the immune homeostasis, leading to the immunopathological process in AIH.

A rare case report of fungal esophagitis combined with giant gastric ulcer in an immunocompetent patient.

RATIONALE: Fungal infection of gastrointestinal (GI) tract is usually seen in immunocompromised patients, but can rarely occur in immunocompetent people in whom no permissive factor is present. PATIENT CONCERNS: We describe a 68-year-old male immunocompetent patient presenting with simultaneous fungal esophagitis and giant gastric ulcer. DIAGNOSES: Repeated endoscopic biopsies were taken from the giant gastric ulcer edge and base and histology demonstrated granulation tissue and pseudohyphal fungal forms. INTERVENTIONS: The patient was treated with fluconazole and omeprazole for 8 weeks. OUTCOMES: After antifungal treatment with fluconazole, the patient's clinical symptoms gradually disappeared with the healing of gastric ulcer, which never recurred in this patient until 3 months after follow-up. LESSONS: Nonhealing gastroesophageal ulcers highlights the importance of repeated endoscopies and biopsies.

A case report of endoscopic therapy for radiation-induced hemorrhagic gastritis in patient with recurrent hepatocellular carcinoma.

RATIONALE: Radiation-induced hemorrhagic gastritis is an infrequent cause of upper gastrointestinal bleeding and difficult to manage. The current standard treatment has not been well established. PATIENT CONCERNS: We described a 32-year-old male patient with hemorrhagic gastritis induced by external radiotherapy for hepatocellular carcinoma recurrence. DIAGNOSES: The endoscopic examination showed a diffuse area of bleeding in the gastric antrum. INTERVENTIONS: After failure of conventional hemostasis treatment, we successfully stopped the hemorrhage with repeated endoscopic argon plasma coagulation (APC) combined with low-dose polyglycerol sclerotherapy. OUTCOMES: The patient was followed up for 6 months to date without recurrence. LESSONS: Based on this case, we think that endoscopic APC combined with low-dose polidocanol sclerotherapy can be tried as a treatment for potentially life-threatening radiation-induced hemorrhagic gastritis.

The Imbalance between Foxp3+Tregs and Th1/Th17/Th22 Cells in Patients with Newly Diagnosed Autoimmune Hepatitis.

This study is aimed at examining the potential role of regulatory T- (Treg-) Th1-Th17-Th22 cells in the pathogenic process of autoimmune hepatitis (AIH). The numbers of Foxp3+Tregs and Th1, Th17, and Th22 cells were measured in 32 AIH patients using flow cytometry. Moreover, a murine model of experimental autoimmune hepatitis (EAH) was also established and used to investigate the function of Treg-Th1-Th17-Th22 cells in disease progression. AIH patients undergoing an active state had significantly decreased numbers of CD3+CD4+CD25+Foxp3+Tregs and increased numbers of CD3+CD4+CD25-Foxp3+T, CD3+CD4+IFN-γ+Th1, CD3+CD4+IL-17+Th17, and CD3+CD4+IL-2+Th22 cells as well as higher levels of Th1/Th17/Th22-type cytokines compared to AIH patients in remission and HC. Additionally, the numbers of CD3+CD4+CD25+Foxp3+Tregs were negatively correlated with the numbers of Th1-Th17-Th22 cells. Also, the serum levels of IL-17A and IL-22 were correlated positively with liver injury (ALT/AST), whereas the serum levels of IL-10 were correlated negatively with hypergammaglobulinaemia (IgG, IgM) in AIH patients. Interestingly, the percentages of spleen Tregs, expression of Foxp3 mRNA, and liver IL-10 levels decreased, whereas the percentages of spleen Th1-Th17-Th22 cells, expression of T-bet/AHR/RORγt mRNA, and liver IFN-γ, IL-17, and IL-22 levels increased in the murine model of EAH. Our findings demonstrated that an imbalance between Tregs and Th1-Th17-Th22 cells might contribute to the pathogenic process of AIH.

Serum Levels of IL-33 and Correlation with IL-4, IL-17A, and Hypergammaglobulinemia in Patients with Autoimmune Hepatitis.

This study investigated the role of IL-33 in the pathogenesis of autoimmune hepatitis (AIH). The levels of IL-33/sST2 and Th1/Th2/Th17-type cytokines were determined by enzyme-linked immunosorbent assay in serum samples obtained from 30 AIH patients and 20 healthy controls (HCs). In addition, a murine model of experimental AIH (EAIH) was established to investigate the role of IL-33 in disease progression. The serum levels of IL-33, sST2, Th17 cytokines (IL-17A), Th1 cytokines (IFN-γ, TNF-α), and Th2 cytokines (IL-4) were significantly elevated in AIH patients compared to HCs. Following immunosuppression therapy, serum levels of IL-33 and sST2 were significantly decreased. Additionally, the serum levels of IL-33 in AIH patients were correlated positively with markers of hypergammaglobulinemia (IgG, IgM, and IgA) and liver injury (γ-GT/ALP). Also, the serum levels of IL-33 in AIH patients were correlated positively with proinflammatory cytokine levels (IL-17A and IL-4). Interestingly, treatment of EAIH mice with a specific IL-33 neutralizing antibody significantly reversed the increasing trend in serum ALT/AST and inhibited the production of the type 2 (IL-4) and type 17 cytokines (IL-17) but not the type 1 cytokine (IFN-γ). Our findings highlight the possible role of the IL-33/sST2 axis in the progression of AIH, opening a new door for developing a novel therapeutic strategy for AIH.

Value of Endoscopic Ultrasonography Combined with CT in Choice of Mediastinoscopic Radical Resection of Esophageal Cancer / 胃肠病学

Background:Mediastinoscopy is an effective method for the treatment of early esophageal cancer with minimal invasiveness and lower risk. Preoperative accurate staging of esophageal cancer is the key for the choice of mediastinoscopic operation as the treatment modality. Aims:To evaluate the value of combination of endoscopic ultrasonography(EUS)with CT for the treatment of esophageal cancer under mediastinoscopy. Methods:Sixty patients with esophageal cancer were enrolled. The TN staging results of esophageal cancer by EUS and CT examination were compared with the results of postoperative TN staging. Patients were divided into mediastinoscopic operation group and conventional operation group, and the operation time,intraoperative bleeding volume,postoperative pleural drainage flow and postoperative hospitalization time of the two groups were compared. Results:The accuracy rates of preoperative EUS examination in assessing T and N stage were 81. 7% and 83. 3% ,respectively;accuracy rates of preoperative CT examination were 60. 0% and 53. 3% , respectively;and accuracy rates of EUS combined with CT were 85. 0% and 86. 7% ,respectively. Compared with conventional operation group,intraoperative bleeding volume[(178. 2 ± 30. 1)mL vs.(232. 0 ± 48. 2)mL,P ﹤ 0. 05], postoperative pleural drainage flow[( 142. 8 ± 22. 5 ) mL vs. ( 256. 0 ± 42. 3 ) mL,P ﹤ 0. 01 ],postoperative hospitalization time[(12. 1 ± 2. 5)days vs. (14. 3 ± 3. 6)days,P ﹤ 0. 05]in mediastinoscopic operation group were significantly decreased,and no significant difference in operation time was found between the two groups[(152. 4 ± 13. 2) minutes vs.(163. 3 ± 25. 5)minutes,P ﹥ 0. 05]. Conclusions:Combination of EUS with CT examination can improve the accuracy of preoperative staging,thus provides an important reference for the choice of treating esophageal cancer by mediastinoscopic operation.