Expanded circulating peripheral helper T cells in primary biliary cholangitis: Tph cells in PBC.

BACKGROUND: Peripheral helper T (TPH) cells, a recently defined subset of Th cells, promote B cell differentiation and antibody production in inflamed tissues. This study investigated whether circulating TPH cells are associated with primary biliary cholangitis (PBC), a typical organ-specific autoimmune disease. METHODS: Twenty PBC patients and 20 age- and sex-matched healthy controls (HCs) were recruited. The circulating TPH cell subsets were analyzed by flow cytometry, and the associations of TPH cells with disease activity and plasma cells were determined. Functional analysis was performed using a TPH and B cell coculture experiment. RESULTS: The frequencies of circulating TPH cells, ICOS+ TPH cells, and CD28+ TPH cells were increased in patients with PBC. Furthermore, the ICOS+ TPH cell level was higher in PBC patients with or without cirrhosis than in HCs, and the level decreased after treatment. Moreover, ICOS+ TPH cell levels correlated positively with specific clinical parameters (including anti-mitochondrial antibodies against M2 antigen (AMA-M2), IgM) and plasma cell levels, suggesting that the TPH cell activation status is associated with the severity of PBC. Coculture results revealed an enhanced ability of TPH cells from PBC patients to induce B cell differentiation. CONCLUSIONS: Elevated numbers of TPH cells may be involved in the pathogenesis of PBC, and the activation status of TPH cells is related to the severity of PBC. Additionally, TPH cells can be used as a useful biomarker for evaluating the progression of PBC and may serve as a therapeutic target for PBC patients in the future.

Helicobacter pylori Infection Increases Frequency of PDCA-1(+) (CD317(+)) B-cell Subsets.

BACKGROUND AND AIMS: As a newly discovered B-cell subset, PDCA-1(+) B cells have been shown to participate in the immune clearance of invading pathogens. The prominence of PDCA-1(+) B cell immunity in the pathogenesis of Helicobacter pylori infection prompted us to explore the potential role of this subset in gastric H. pylori infection. METHODS: H. pylori infection was determined by (14)C-urea breath test and Western blot. The frequency of the different sub-compartments of PDCA-1(+) B cells and their relation to serum cytokines was determined in 33 H. pylori-infected and 14 uninfected patients and in 12 healthy controls (HC). RESULTS: In comparison to uninfected individuals, there was a significantly increased frequency of PDCA-1(+) B cells, PDCA-1(+)IgM(+) B cells, CD93(+)PDCA-1(+) B cells, CD93(+)PDCA-1(+)IgM(+) B cells, CD137(+)PDCA-1(+) B cells and CD137(+)PDCA-1(+)IgM(+) B cells were detected in patients with H. pylori infection, corresponding to increased levels of serum IFN-α and IgM in this group. Compared with H. pylori-positive (HP(+)) chronic non-atrophic gastritis patients, a larger proportion of PDCA-1(+) B cells, CD93(+)PDCA-1(+) B cells and CD137(+)PDCA-1(+) B cells were observed in HP(+) patients suffering from atrophic gastritis or HP(+) peptic ulcers. CONCLUSIONS: The frequency of the PDCA-1(+) B cell compartment is increased during H. pylori infection. Our data support the potential role of this B-cell subset in the pathogenesis of H. pylori-dependent gastritis.

Relationship between serum aminotransferase levels and metabolic disorders in northern China.

BACKGROUND/AIMS: Increasing evidence suggests an association between elevated serum aminotransferase levels and metabolic disorders (metabolic syndrome, hyperlipidemia and diabetes mellitus). However, the significance of relatively low levels of aminotransferases in relation to metabolic disorders has not been fully investigated in the general population. We investigated the association between serum aminotransferase levels and metabolic disorders using data from a survey in Jilin Province, China. MATERIALS AND METHODS: In 2007, a prospective survey was conducted throughout Jilin, China, covering both urban and rural areas. A total of 3835 people, 18-79 years old, were undergoing real-time ultrasonography, blood tests, and interviews with a structured questionnaire. RESULTS: Serum aminotransferase levels within the normal range were associated with metabolic syndrome independent of age, occupation, cultural and educational level, income, body mass index, waist circumference, smoking, and alcohol intake. Compared with the lowest level (< 20 IU/L), the adjusted odds ratios for alanine aminotransferase levels of 20-29, 30-39, 40-49, and >50 IU/L were 1.92, 2.50, 2.97, and 3.52 in men, and 1.38, 1.54, 3.06, and 2.62 in women, respectively. Near-normal serum aminotransferase levels associated with hyperlipidemia, non-alcoholic fatty liver disease, and diabetes mellitus were also found in the study. CONCLUSIONS: Normal to near-normal serum aminotransferase levels are associated with metabolic disorders. Serum alanine aminotransferase levels of 21-25 IU/L for men and 17-22 IU/L for women are suggested as cut-off levels that detect metabolic disorders affecting the liver.