Amolak Bansal

Low-titre auto-antibodies predict autoimmune disease during interferon-alpha treatment of chronic hepatitis C.

Background: In this study, we determined whether low‐titre auto‐antibodies are a risk factor for the development of autoimmune disease during interferon‐α (IFNα) therapy for chronic hepatitis C (CHC) infection.

INTRADERMAL RECOMBINANT HEPATITIS B VACCINE FOR HEALTHCARE WORKERS WHO FAIL TO RESPOND TO INTRAMUSCULAR VACCINE

OBJECTIVE To study the humoral immune responses, safety, and tolerability of intradermal recombinant hepatitis B vaccination in healthcare workers (HCWs) nonresponsive to previous repeated intramuscular vaccination. DESIGN An open, prospective, before-after trial. SETTING A tertiary referral hospital and surrounding district health service in Queensland, Australia. PARTICIPANTS Hospital and community HCWs nonresponsive to previous intramuscular hepatitis B vaccination. METHODS Intradermal recombinant hepatitis B vaccine was administered every second week for a maximum of 4 doses. Hepatitis B surface antibody (anti-HBs) responses were assessed 2 weeks after each dose. RESULTS Protective anti-HBs levels developed in 17 (94%) of 18 study subjects. Three doses resulted in seroconversion of all responding subjects and the highest geometric mean antibody concentration. The vaccine was well tolerated. CONCLUSION More than 90% of previously nonresponsive HCWs responded to intradermal recombinant hepatitis B vaccine with protective anti-HBs levels.

Histologic and immunohistochemical responses after aortic valve allografts in the rat

BACKGROUND Human aortic valve allografts elicit a cellular and humoral immune response. It is not clear whether this is important in promoting valve damage. We investigated the changes in morphology, cell populations, and major histocompatibility complex antigen distribution in the rat aortic valve allograft. METHODS Fresh heart valves from Lewis rats were transplanted into the abdominal aorta of DA rats. Valves from allografted, isografted, and presensitized recipient rats were examined serially with standard morphologic and immunohistochemical techniques. RESULTS In comparison with isografts, the allografts were infiltrated and thickened by increased numbers of CD4+ and CD8+ lymphocytes, macrophages, and fibroblasts. Thickening of the valve wall and leaflet and the density of the cellular infiltrate was particularly evident after presensitization. Endothelial cells were frequently absent in presensitized allografts whereas isografts had intact endothelium. Cellular major histocompatibility complex class I and II antigens in the allograft were substantially increased. A long-term allograft showed dense fibrosis and disruption of the media with scattered persisting donor cells. CONCLUSIONS The changes in these aortic valve allograft experiments are consistent with an allograft immune response and confirm that the response can damage aortic valve allograft tissue.

Expression of cytokines and factors modulating apoptosis by human sinusoidal leucocytes

BACKGROUND/AIMS Liver sinusoids contain a large population of spontaneously cytotoxic cells (NK cells), CD8+ T cells and macrophages. The physiological role of these leucocytes remains unclear. They may participate in immune surveillance and peripheral tolerance by deleting tumour cells, virus-infected cells and activated T cells as they traffic through the liver. In order to gain further information about the function of these leucocytes within the hepatic sinusoids, we examined their production of immunomodulatory cytokines and apoptosis-related molecules. METHODS Semi-quantitative polymerase chain reaction and immunohistochemistry were used to determine the spontaneous production of cytokines and apoptosis-related molecules by sinusoidal leucocytes isolated from donor liver preservation solution. RESULTS In comparison with matched peripheral blood mononuclear cells, sinusoidal leucocytes produced more mRNA for IL-10, IL-15, TNF-alpha, IL-18, IFN-gamma, FasL, perforin and granzyme. IL-4 and IL-12 were not detected and IL-2 was only faintly detected in the liver-derived CD4+ population. Less bcl-2 was expressed in liver-derived CD4+ and CD8+ cells in comparison with matched peripheral blood cell populations. CONCLUSIONS The cytokines produced spontaneously by sinusoidal leucocytes are consistent with their high level of activation and spontaneous cytotoxicity. Their strong expression of apoptosis-mediating molecules (FasL, perforin, granzyme and TNF-alpha) support a role for these cells in immune surveillance and peripheral tolerance induction.

Serum endometrial IgG antibodies and soluble CD23 concentrations in patients with endometriosis

Objective. Serum endometrial antibodies have been found inconsistently in patients with endometriosis. Soluble CD23 is elevated in diseases associated with B cell activation. We evaluated serum levels of soluble CD23 and endometrial IgG antibodies in patients with endometriosis to determine whether there is B cell activation in this condition.

Serum and blister fluid cytokines and complement proteins in a patient with Henoch Schönlein purpura associated with a bullous skin rash

A case is presented of an adult with Henoch Schönlein purpura (HSP) with widespread bullous skin lesions in whom serum and bullous fluid (BF) cytokines and complement proteins were analysed. In both serum and BF the total haemolytic complement was subnormal. Soluble CD23 (sCD23), which is important in B cell activation and proliferation, was over 13 times higher in the BF compared with serum. The serum and BF levels of interleukin (IL) 1, IL6, IL10, tumour necrosis factor α and interferon γ were within the normal serum range of 30 healthy control subjects simultaneously analysed. The raised levels of sCD23 in BF suggest dysregulated humoral immunity in the cutaneous lesions of HSP.

Peritoneal fluid from ovarian cancer patients stimulates MUC1 epithelial mucin expression in ovarian cancer cell lines

The MUC1 epithelial mucin is a transmembrane glycoprotein that is frequently but variably over‐expressed by adenocarcinomas. It is used as a diagnostic serum tumour marker and is a candidate target for tumour immunotherapy. Peritoneal fluid (PF) samples from ovarian cancer patients were investigated for their ability to modulate MUC1 expression in 6 ovarian cancer cell lines which showed a range from very low to high endogenous MUC1 expression. Cell lines were cultured in 20% PF for 4 days, fixed in situ and MUC1 assayed by ELISA. MUC1 expression was stimulated by some PF samples in 5 of 6 lines tested. MUC1 expression in the PE04 cell line (very low endogenous expression) was increased by 35 of 36 PFs tested (p < 0.05); stimulation varied between PFs but was greater than with 100 IU/mL hu‐r‐γ‐interferon. Western blotting confirmed the stimulation of MUC1 in PE04 cells and FACS showed an increase in the proportion of cells expressing MUC1. The active factor was partially purified by gel filtration and was shown to stimulate PE04 cells in a dose‐dependent manner. Concentrations of IL1β, IL4, IL6, IL8, IL10, TNF‐α, TGF‐β and GM‐CSF were often very high in PF and varied substantially between different PF samples but did not correlate with the degree of MUC1 stimulatory activity. Int. J. Cancer 76:393–398, 1998.© 1998 Wiley‐Liss, Inc.

Serum levels of sCD23, interleukin‐10 and interferon‐γ in patients with coeliac disease

The role of cellular and humoral immunity coeliac disease was investigated by the measurement of serum levels of interleukin‐10 (IL‐10), interferon‐gamma (IFN‐γ) and soluble CD23 (sCD23). Coeliac disease was diagnosed by duodenal biopsy and response to a gluten‐free diet (GFD). The results were compared with age and sex‐matched patients with non‐specific upper gastrointestinal symptoms and normal duodenal histology. While the levels of serum IL‐10 were significantly elevated (P < 0.01) in patients with coeliac disease taken as a whole, the levels of serum IFN‐γ were normal and sCD23 significantly decreased (P < 0.002). The median serum sCD23 was significantly lower in the coeliac disease patients not on a GFD compared with those asymptomatic on a GFD (P < 0.03) and the control group (P < 0.0004). The coeliac disease patients on a GFD also had significantly lower serum sCD23 and higher IL‐10 compared with the control group (P < 0.01 and P < 0.015). There was no significant difference in the serum IL‐10 between the coeliac disease patients on a GFD and those not on a GFD and between the latter and the control group. The low levels of serum sCD23 in coeliac disease suggest diminished humoral immunity and, conversely, exaggerated cellular immunity. The aetiology of the raised levels of IL‐10 in coeliac disease is unclear and similar to that observed in patients with inflammatory bowel disease. However, this may represent a regulatory response to the elevated levels of proinflammatory cytokines described in coeliac disease. A combination of diminished sCD23 and raised IL‐10 is clearly unusual as both are associated with Th2‐type functions. The possible causes of this finding are discussed.