Functionally aberrant dendritic cell subsets and expression of DC-SIGN differentiate acute from chronic HBV infection

Background

Dendritic cells (DCs) promote pathogen recognition, uptake and presentation of antigen through DC-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and toll-like receptors (TLRs).

Aims and Objectives

We aimed to study temporal changes in DCs, TLRs and DC-SIGN during acute viral hepatitis B (AVHB) infection and compare them to chronic (CHB) and to investigate the earliest time point of activated pathogen recognition receptors in hepatitis B viral infection.

Methods

We measured the frequencies of circulating myeloid (mDC) and plasmacytoid (pDC) dendritic cells and IFN-α production along with the expression of DC-SIGN and Toll Like Receptors (TLR's) in HBV patients at different time points. Also investigated in healthy volunteers, the dynamic changes in TLRs expression after receiving hepatitis B vaccine.

Results

On follow-up of AVHB patients, we found the mDC population was significantly higher at week 4 and 6 (p < 0.02, 0.01), whereas the pDC population was unchanged at week 6 compared with week 0. Whereas frequencies of mDCs and pDCs were found to be elevated in AVHB and CHB patients than HC (p < 0.00 and 0.01, respectively) but was comparable among AVHB vs CHB. The DCs in CHB patients were functionally impaired with significantly low IFN-α production and low DCSIGN expression (p < 0.04 and 0.00, respectively). Even after stimulation by TLR agonists, no change was found in IFN-α production in CHB patients. MyD88 and IL-6, IFN-α mRNA levels were also found down-regulated. Interestingly, on follow-up after HBV vaccine, TLRs expression was found high at day 3 after vaccination.

Discussion

The initial events of immune activation might be responsible for modulating immune response. These novel observations would pave the way for the development of antiviral strategies for chronic HBV infection.

     

CEACAM-1 Induced CSF3-receptor Downregulation in Bone Marrow Associated With Refractory Neutropenia in Advanced Cirrhosis

Background and Aims: Cirrhosis patients exhibit cyto-penia, and, at times refractory neutropenia to granulocyte colony-stimulating factor (G-CSF), which acts th...     

A 40‐Year‐Old Male with An Intraventricular Tumor

Combined tumors showing histologic features of both ependymoma and subependymoma have been described. In this report we present a case of combined tanycytic ependymoma with foci of subependymoma (WHO grade II), occurring in a 40 year‐old male, which arose in the wall of the lateral ventricle. The tanycytic ependymoma component showed elongated fibrillary cells with a fascicular pattern of growth, while the subependymoma component showed clustered cell bodies surrounded by a fibrillary stroma with a microcystic appearance. We consider the present case to be an unusual example of tanycytic ependymoma; which to the best of our knowledge has not been associated with a subependymoma.     

Circulating Tregs correlate with viral load reduction in chronic HBV-treated patients with tenofovir disoproxil fumarate

Limited response to current hepatitis B virus (HBV) drugs is possibly due to inadequate host cytotoxic cellular responses. Circulating Tregs have been shown to be associated with chronicity of HBV infection, but their profile during antiviral therapy has not been studied. We analyzed the frequency and effect of Tregs on cellular immune responses against HBV in 35 chronic hepatitis B eAg−ve and eAg+ve patients treated with tenofovir 300 mg/day. Frequency of Tregs and their modulatory role in cytokine-secreting cells were determined after stimulation with HBsAg or HBcAg in the absence or presence of Tregs and after blockage of PD-1/PDL-1 in peripheral blood mononuclear cells (PBMCs). Prior to therapy, eAg−ve patients had lower HBV DNA levels, reduced CD8 T cells, increased Tregs, and T cells expressing PD1. After 12 weeks of therapy, >2 log HBV viral reduction was observed in both groups, along with an increase frequencies of CD8 T cells in eAg−ve patients and increased expression of chemokine receptors/Toll-like receptors in both groups. PD-1 expression on CD8 cells in PBMCs was decreased in both groups during therapy but not on Tregs. In eAg–ve group, sustained increase of Tregs was observed till week 12, which declined at week 24. In both groups, after 24 weeks, depletion of CD4⁺CD25⁺ Tregs from PBMCs enhanced HBV-specific T cell responses, and blockage of PD-1/PDL1 pathway did enhance pro-inflammatory cytokine production in eAg+ve patients but not in eAg−ve. We conclude that Tregs induced by HBV replication in vivo are expanded in eAg−ve patients more. Reduction in HBV DNA by tenofovir partially restored adaptive immune responses and also reduced the Tregs. Blockage of PD-1/PDL1, enhanced cytokine production in eAg+ve patients but not in eAg−ve, suggests that distinctly different immunologic mechanisms are involved in eAg+ve and eAg−ve patients.     

Gene expression profiles of T cells from hepatitis E virus infected patients in acute and resolving phase

Background and Aims  

Approximately 50% of acute viral hepatitis in young adults and in pregnant women is due to hepatitis E virus (HEV) infection in developing countries. T cell-mediated immune injury probably plays a key role in the pathogenesis of acute hepatitis illness. However, there is a paucity of data on the global gene expression programs activated on T cells, which are subsequently responsible for T cell recruitment to the liver and triggering of immune injury.     

Muscle and nerve involvement in granulomatous mycosis fungoides

Occasional cases of peripheral neuropathy have been reported in classic mycosis fungoides. A rare variant of mycosis fungoides is the granulomatous form. We describe the occurrence of myopathy and peripheral neuropathy in a young woman who had skin lesions since the age of 12 years. At the age of 20 years they were diagnosed as granulomatous mycosis fungoides. The skin lesions resolved with interferon therapy and radiation. She then presented with cardiac and pulmonary symptoms and signs that were initially thought to be due to sarcoidosis or systemic vasculitis. A nerve and muscle biopsy showed granulomatous mycosis fungoides. To our knowledge, involvement of muscle and nerve by granulomatous mycosis fungoides has not been reported previously. Early reports suggested a favorable prognosis for the granulomatous subtype of mycosis fungoides. Based on a literature review and the course in our case, however, granulomatous mycosis fungoides seems to be an indicator of aggressive disease and ultimately a poor prognosis.