Objective:To investigate the changes of non-specific and HBV core antigen (HBcAg)-specific Th9 cells, and intereleukin-9 (IL-9) in HBV-infected patients, and to assess the influence of Th9 cells on CD8 + T cell function. Methods:Twelve patients with acute hepatitis B (AHB) and 58 with chronic hepatitis B (CHB), who were hospitalized in the First Affiliated Hospital of Xinxiang Medical University between January 2018 and January 2019, were enrolled in this study. Twenty healthy subjects negative for HBsAg were selected as controls. Peripheral blood mononuclear cells (PBMCs) and plasma samples were isolated. Non-specific Th9 cells (CD3 + CD4 + IL-9 + ) and HBcAg-specific Th9 cells were analyzed by flow cytometry. Plasma IL-9 level was measured by enzyme linked immunosorbent assay. CHB patients received tenofovir disoproxil fumarate (TDF) antiviral therapy. The changes of non-specific Th9 cells, HBcAg-specific Th9 cells and plasma IL-9 level were assessed 48 weeks after TDF therapy. CD4 + CCR4 -CCR6 -CXCR3 -(Th9) cells and CD8 + T cells were isolated from 12 HLA-A2 restricted CHB patients and co-cultured with HepG2.2.15 cells with the presence of anti-IL-9 neutralizing antibody. The percentage of dead HepG2.2.15 cells and the levels of IFN-γ and TNF-α were detected. Student′s t test, one-way analysis of variance or SNK- q test was used for statistical comparison between groups. Results:There were no significant differences in non-specific Th9 cells or plasma IL-9 level among AHB patients, CHB patients and healthy controls ( P>0.05). HBcAg-specific Th9 cells was down-regulated in CHB patients when compared with AHB patients [(2.49±0.61)% vs (3.19±0.62)%, P<0.001]. The percentage of HBcAg-specific Th9 cells was negatively correlated with HBV DNA ( r=-0.385, P=0.003), but not correlated with ALT ( P>0.05) in CHB patients. TDF therapy for 48 weeks remarkably elevated the HBcAg-specific Th9 cells [(2.94±0.48)%, P<0.001], however, did not affect non-specific Th9 cells or plasma IL-9 level ( P>0.05) in CHB patients. The cytotoxicity of HBcAg-specific Th9 cells was low in CHB patients. However, HBcAg-specific Th9 cells could induce enhanced cytotoxicity of CD8 + T cells to HepG2.2.15 cells, which manifested as increased percentage of dead HepG2.2.15 cells and higher levels of IFN-γ and TNF-α. Anti-IL-9 neutralizing antibody reduced the enhancement of CD8 + T cell cytotoxicity by HBcAg-specific Th9 cells ( P<0.001). Conclusions:Chronic HBV infection might suppress the level and function of HBcAg-specific Th9 cells, resulting in persistent infection.

BACKGROUNDThe high blood homocysteine (Hcy) levels found in patients with hyperhomocysteinemia (HHcy) have been implicated in an increased risk of cardiovascular disease morbidity and mortality in end-stage renal disease (ESRD). This study investigated the association of HHcy with progression of IgA nephropathy.

METHODSWe analyzed 108 participants newly diagnosed with IgA nephropathy between August 2005 and August 2007 in the Department of Nephrology, Chinese People's Liberation Army General Hospital. The association between clinicopathological factors and the Hcy levels were analyzed by Logistic regression and those with ESRD risk were analyzed by Cox regression.

RESULTSPatients were aged (35.71 ± 10.73) years and included 45.71% women and 12.04% patients with HHcy. In multivariate Logistic regression analysis, HHcy was associated with arterial lesions (OR 2.60; 95% CI 1.55 ± 4.34; P < 0.001) even when age, body mass index, estimated glomerular filtration rate, mean arterial pressure, and initial proteinuria were taken into account. Mean follow-up was (67.37 ± 16.21) months. HHcy was also associated with worse ESRD-free survival (HR 4.71; 95% CI 1.45 to 15.31; P = 0.010).

CONCLUSIONHHcy is associated with the risk of intrarenal arterial lesions and may be useful for estimating the prognosis of IgA nephropathy.

Adult ; Body Mass Index ; Female ; Glomerular Filtration Rate ; physiology ; Glomerulonephritis, IGA ; etiology ; physiopathology ; Humans ; Hyperhomocysteinemia ; complications ; physiopathology ; Logistic Models ; Male ; Middle Aged ; Retrospective Studies